The Foot in Diabetes

The Foot in Diabetes

Fifth Edition

Edited by

Andrew J. M. Boulton
Division of Diabetes, Endocrinology and Gastroenterology
University of Manchester, Manchester, UK;
Manchester Royal Infirmary, Manchester, UK;
Diabetes Research Institute, University of Miami, Miami, FL, USA

Gerry Rayman
Diabetes Centre, Ipswich Hospital, Ipswich, UK;
University of East Anglia, Norwich, UK;
University of Suffolk, Ipswich, UK

Dane K. Wukich
Department of Orthopaedic Surgery
University of Texas Southwestern Medical Center
Dallas, TX, USA
This edition first published 2020
© 2020 John Wiley & Sons Ltd

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Library of Congress Cataloging‐in‐Publication Data

Names: Boulton, A. J. M. (Andrew James Michael), editor. | Rayman, Gerry, editor. |
Wukich, Dane K, editor.
Title: The foot in diabetes / edited by Andrew J. M. Boulton, Gerry
Rayman, Dane K. Wukich.
Other titles: Foot in diabetes (Boulton) | Diabetes in practice.
Description: Fifth edition. | Hoboken, NJ : Wiley-Blackwell, 2020. |
Series: Diabetes in practice | Includes bibliographical references and index.
Identifiers: LCCN 2019053492 (print) | LCCN 2019053493 (ebook) | ISBN
9781119445814 (hardback) | ISBN 9781119445883 (adobe pdf) | ISBN
9781119445838 (epub)
Subjects: MESH: Diabetic Foot–therapy | Diabetic Foot–etiology
Classification: LCC RD563 (print) | LCC RD563 (ebook) | NLM WK 835 |
DDC 617.5/85–dc23
LC record available at https://lccn.loc.gov/2019053492
LC ebook record available at https://lccn.loc.gov/2019053493

Cover Design: Wiley

Cover Images: Wound of diabetic foot © ittipon/Shutterstock, X-ray image © ChooChin/Shutterstock,
Diabetic ulcer © Janthiwa Sutthiboriban/Shutterstock, Diabetic ulcer on left foot © Janthiwa Sutthiboriban/Shutterstock,
Eczema from diabetes © srisakorn wonglakorn/Shutterstock

Set in 9.5/12.5pt STIX Two Text by SPi Global, Pondicherry, India

10 9 8 7 6 5 4 3 2 1
 v

Contents

List of Contributors xv
Preface xix
Introduction xxi

1 Epidemiology and Economic Impact of Foot Ulcers 1

Edward J. Boyko and Matilde Monteiro-Soares
1.1 ­Introduction 1
1.2 ­Diabetic Foot Ulcer (DFU) Definition 1
1.3 ­DFU Classification 2
1.4 ­DFU Incidence and Prevalence 3
1.5 ­DFU Recurrence 5
1.6 ­Risk Factors for Diabetic Foot Ulcers and Lower Extremity Amputation 6
1.7 ­Diabetic Foot Ulcer Outcomes 7
1.8 ­Economic Considerations 9
­ References 10

2 Cost of Diabetic Foot Disease in England 17

Marion Kerr
2.1 ­Introduction 17
2.2 ­Human Costs 17
2.3 ­Financial Costs 20
2.4 ­Why Measure Costs? 22
2.5 ­Establishing Healthcare Priorities 22
2.6 ­Conclusions 25
­References 26

3 Epidemiology of Amputation and the Influence of Ethnicity 31

Caroline A. Abbott
3.1 ­Why Study the Epidemiology of LEA? 31
3.2 ­LEA Incidence Study Design: The Risk of Bias 32
3.3 ­LEA Risk Assessment Study Design 32
3.4 ­Risk Factors for LEA 33
3.5 ­Incidence Rates of LEA 34
3.6 ­International and Regional Differences 34
3.7 ­Time Trends in LEA Rates 34
vi Contents

3.8 ­ thnic Differences in Diabetes-Related LEA 35

E
3.9 ­Ethnic Differences in Diabetes-Related LEA Risk 35
3.10 ­Indian Asians 38
­ References 38

4a The Diabetic Foot Worldwide: India 43

M. Viswanathan
4a.1 ­Introduction 43
4a.2 ­Epidemiology of Diabetes in India 43
4a.3 ­Socio Economic Burden Due to Diabetes 43
4a.4 ­Common Risk Factors for Amputation in India 43
4a.5 ­Diagnosing High Risk Feet in Developing Countries 44
4a.6 ­Comparison in Risk Factors between India and the Western World 44
4a.7 ­DFI as a Cause for Declining Kidney Function 44
4a.8 ­Helping People with Amputation Cope Up with the Disability 44
­References 45

4b The Diabetic Foot Worldwide: Pakistan 47

Abdul Basit
4b.1 ­Introduction 47
4b.2 ­Concept of Multidisciplinary Diabetic Foot Care Team (MDFCT) 47
4b.3 ­Nationwide Diabetic Foot Programme (Step by Step-[SbS]) 48
4b.4 ­Footwear for Every Diabetic (FED) 48
4b.5 ­Further Steps Ahead of SbS 49
­ References 49

4c The Diabetic Foot Worldwide: Sub-Saharan Africa 51

Zulfiqarali G. Abbas
4c.1 ­Introduction 51
4c.2 ­Pathophysiology of Foot Ulcers 52
4c.3 ­Peripheral Neuropathy (PN) 52
4c.4 ­Peripheral Arterial Diseases (PAD) 53
4c.5 ­Foot Ulceration in SSA 54
4c.6 ­Foot Infection 55
4c.7 ­Amputation 56
4c.8 ­Mortality 56
4c.9 ­Prevention 56
4c.10 ­Conclusions 58
­References 58

4d Burden of Diabetic Foot Disease in Brazil 61

Hermelinda C. Pedrosa and Luciana R. Bahia
­ References 64

4e Diabetic Foot in Romania and Eastern Europe 67

Norina Alinta Gâvan and C. I. Bondor
4e.1 ­Introduction 67
4e.2 ­The Aim 67
 Contents vii

4e.3 ­ iabetic Foot in Romania 67

D
4e.4 ­Diabetic Foot in Eastern Europe 70
4e.5 ­Conclusions 71
­ References 71

4f Diabetic Foot Worldwide: Pacific Region 75

Shigeo Kono
­ References 76

4g The Diabetic Foot Worldwide: Middle East 79

Samir H. Assaad-Khalil
4g.1 ­The Burden of Diabetic Foot Disease (DFD) in the Middle
East (ME) 79
4g.2 ­Specific Regional Barriers to Healthy Feet and Foot Care 80
4g.3 ­Misconceptions 81
4g.4 ­Footwear 81
4g.5 ­Foot Care, Education and Awareness 81
­References 82

4h The Diabetic Foot Worldwide: Australasia 85

Peter A. Lazzarini
4h.1 ­Introduction 85
4h.2 ­Australia 85
4h.3 ­New Zealand 86
4h.4 ­Pacific Islands 86
4h.5 ­Conclusion 87
­ References 87

5 Diabetic Neuropathy 89
Dinesh Selvarajah, Gordon Sloan, and Solomon Tesfaye
5.1 ­Epidemiology 89
5.2 ­Classification 89
5.3 ­Symmetrical Neuropathies 91
5.4 ­Asymmetrical Neuropathies 95
5.5 ­Pathogenesis of Distal Symmetrical Neuropathy 97
5.6 ­Management of Diabetic Neuropathy 98
­References 101

6 The Pathway to Ulceration: Aetiopathogenesis and Screening 105

Andrew J.M. Boulton
6.1 ­Introduction 105
6.2 ­Peripheral Arterial Disease (PAD) 106
6.3 ­Diabetic Neuropathy 107
6.4 ­Neuropathy: The Major Contributory Factor in Ulceration 109
6.5 ­Other Risk Factors for Foot Ulceration 109
6.6 ­Assessment of Foot Ulcer Risk 111
6.7 ­The Pathway to Ulceration 116
viii Contents

6.8 ­ echanical Factors and Neuropathic Foot Ulceration

M 118
6.9 ­The Patient with Sensory Loss 120
­ References 120

7 Biomechanics of the Diabetic Foot for the Uninitiated 125

S.A. Bus and J.S. Ulbrecht
7.1 ­Introduction 125
7.2 ­The Concept of Pressure and its Measurement 125
7.3 ­The Role of Elevated Plantar Pressure in Foot Ulceration 126
7.4 ­Mechanisms of Elevated Plantar Pressure 128
7.5 ­Foot Biomechanics in Treating a Plantar Foot Ulcer 130
7.6 ­Biomechanical Issues in Preventing a Foot Ulcer 132
7.7 ­Summary 133
­ References 134

8 Psychological and Behavioural Aspects of Diabetic Foot Ulceration 139

Loretta Vileikyte and Ryan T. Crews
8.1 ­The Role of Psychological and Behavioural Factors in DFU Development 139
8.2 ­The Role of Psychological and Behavioural Factors in DFU Healing 142
8.3 ­The Impact of DFUs on Patients’ Health Status and QoL 146
8.4 ­Measuring QoL in DFU Patients: Generic, DFU-Specific or Combined
Approach? 147
­ References 148

9 What Role for the Plain Radiograph of the Diabetic Foot? 153
Richard William Whitehouse
9.1 ­Introduction 153
9.2 ­Pathologies 157
9.3 ­Summary 166
­ References 167

10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography and

Magnetic Resonance Imaging of the Diabetic Foot 169
Aparna Komarraju and Avneesh Chhabra
10.1 ­Introduction 169
10.2 ­Pathophysiology of Diabetic Foot Disease 170
­References 183

11 Gait and Exercise Training in Diabetic Peripheral Neuropathy 187

Neil D. Reeves
11.1 ­Introduction 187
11.2 ­Gait Characteristics of People with Diabetes 187
11.3 ­Muscle Forces and the Biomechanics of Gait in Diabetes 188
11.4 ­Biomechanical Strategies to Alter Gait in Diabetic Peripheral Neuropathy 190
 Contents ix

11.5 ­ alls and Diabetic Peripheral Neuropathy 193

F
11.6 ­Biomechanical Factors Leading to Increased Fall Risk 193
11.7 ­Diabetic Peripheral Neuropathy and Balance during Gait 194
11.8 ­Exercise and Diabetic Peripheral Neuropathy 196
11.9 ­Effects of Exercise in Patients with Diabetic Peripheral Neuropathy on Gait
and Balance 197
11.10 ­The Case for Resistance Exercise Training 198
­ References 198

12 Smart Technology for the Diabetic Foot in Remission 201

Bijan Najafi and David G. Armstrong
12.1 ­Background 201
12.2 Technologies to Guide the Prescription of Footwear-Related Offloading
Treatments 203
12.3 ­Technologies to Facilitate Triaging those at High Risk of DFU 204
12.4 ­Technologies to Manage Dose of Physical Activities in People with Diabetes
and Insensate Foot 211
12.5 ­Using Technology to Improve Patient Education for Effective Prevention
of Diabetic Foot Ulcers 214
12.6 ­Mobile Health (mHealth) to Manage Diabetic Foot Ulcers 215
12.7 ­Internet of Things and Remote Management of Diabetic Foot Ulcers 216
12.8 ­Technologies to Facilitate Delivering of Therapy at Home and Reduce Risk
of DFU 217
12.9 ­Conclusion 218
­References 219

13 How to Assess the Quality of Clinical Trials for Diabetic Foot Ulcer
Therapies 225
Fran Game and William Jeffcoate
13.1 ­Introduction 225
13.2 ­Hierarchy of Evidence 226
13.3 ­Items to Be Considered in Assessing Trials of Diabetic Foot Ulcer
Therapies 227
13.4 ­The Population 227
13.5 ­The Person and Limb 228
13.6 ­The Ulcer 229
13.7 ­The Therapy 230
13.8 ­Outcomes 230
13.9 ­Adverse Events 231
13.10 ­21 Point Checklist 231
­ References 233
x Contents

14a Bypass in Diabetic Peripheral Artery Disease 235

Neal R. Barshes and Joseph L. Mills
14a.1 ­Identifying Significant PAD Amongst Patients Presenting with Foot
Ulcers 235
14a.2 ­Relative Benefits and Risks: Identifying Patients Who May Benefit from a Leg
Bypass Operation 237
14a.3 ­Evaluating Relevant Vascular Anatomy for Planning a Bypass
Operation 239
14a.4 ­The Operation and Early In-Hospital Recovery 241
14a.5 ­Follow-Up After a Leg Bypass Operation 243
­ References 243

14b Surgery or Endovascular Intervention in Diabetic Peripheral

Vascular Disease 247
Edward Y. Woo and Misaki M. Kiguchi
14b.1 ­Introduction 247
14b.2 ­Background 247
14b.3 ­Diagnosis 248
14b.4 ­Management 250
14b.5 ­Endovascular Revascularization 250
14b.6 ­Results 253
14b.7 ­Complications 254
14b.8 ­Conclusion 254
­ References 255

15 Inpatient Diabetic Foot Care: A UK Perspective 259

Gerry Rayman
15.1 ­Introduction 259
15.2 ­The Burden of Inpatient Diabetes 260
15.3 ­The Burden of Inpatient Diabetic Foot Disease 260
15.4 ­Recommended Foot Care for Inpatients with Diabetes 261
15.5 ­Summary 262
­References 263

16 Diagnosis and Management of Infection in the Diabetic Foot 265

Edgar J.G. Peters and Benjamin A. Lipsky
16.1 ­Introduction 265
16.2 ­Pathophysiology of Infections in Persons with Diabetes Mellitus 265
16.3 ­Risk Factors for DFI 266
16.4 ­Clinical Signs and Symptoms 266
16.5 ­Classification 267
16.6 ­Microbiology 268
16.7 ­Treatment 269
16.8 ­IWGDF Grade 4 (Severe) Infections 274
16.9 ­Osteomyelitis 275
­References 280
 Contents xi

17 Surgical Approach to Diabetic Foot Infections 287

Katherine M. Raspovic, Javier La Fontaine, and Lawrence Lavery
17.1 ­Introduction 287
17.2 ­Initial Evaluation 288
17.3 ­Initial Surgical Intervention 290
17.4 ­After Initial Surgical Intervention 293
17.5 ­Staged Surgical Intervention and Wound Closure 294
17.6 ­Surgical Offloading 296
17.7 ­Soft Tissue/Tendon Balancing and Definitive Osseous Surgical
Reconstruction 296
17.8 ­Decision for Proximal Level Amputation 297
17.9 ­Conclusions 298
References 298

18 The Evidence Base for the Choice of Dressings in the Management

of Diabetic Foot Ulcers 301
William J. Jeffcoate, Patricia E. Price, and Frances L. Game
18.1 ­The Problems 301
18.2 ­Quality of Evidence 302
18.3 ­The Definition of a Dressing 302
18.4 ­The Roles of the Dressing 303
18.5 ­Basic Aspects of Wound Care 304
18.6 ­Evidence for Potential Contributions of Dressings and Wound Applications
to Improve Wound Healing 304
18.7 ­Other Therapies which May Modulate Healing of Chronic Wounds 306
18.8 ­Summary 307
­ References 308

19 Pathogenesis of Charcot Neuroarthropathy and Acute Management 311

N.L. Petrova and Michael E. Edmonds
19.1 ­Introduction 311
19.2 ­Pathogenesis of CN 311
19.3 ­Acute Management of CN 316
19.4 ­Conclusions 318
­ References 319

20 Surgical Reconstruction of the Charcot Foot 323

George Liu, Katherine Raspovic, and Dane Wukich
20.1 ­Introduction 323
20.2 ­Indications for Surgical Reconstruction 323
20.3 ­Radiographic Predictors for Ulceration 325
20.4 ­Timing of Surgery 326
20.5 ­Preoperative Medical Workup 327
20.6 ­Glycemic Control 327
20.7 ­Vitamin D 328
20.8 ­Renal Function 328
xii Contents

20.9 ­ rocedures/Outcome Studies 328

P
20.10 ­Outcomes of Charcot Reconstruction 334
20.11 ­Summary of Evidence Based Recommendations 335
­ References 336

21 Amputation in the Diabetic Foot 345

Michael S. Pinzur and Adam P. Schiff
21.1 ­Introduction 345
21.2 ­Impediments to Rehabilitation in the Diabetic Amputee 345
21.3 ­The Lower Extremity as an Organ of Weight Bearing 346
21.4 ­Metabolic Cost of Walking with an Amputation 346
21.5 ­Limb Salvage vs. Amputation 347
21.6 ­Amputation Level Selection 348
21.7 ­The Terminal Organ of Weight Bearing 348
21.8 ­The Soft Tissue Envelope 351
21.9 ­Tissue Management 351
21.10 ­Outcomes Following Amputation 352
21.11 ­Surgical Amputation Levels 352
21.12 ­Lesser Toe Amputation 353
21.13 ­Ray Resection 353
21.14 ­Midfoot Amputation 355
21.15 ­Hindfoot Amputation 355
21.16 ­Symes’s Ankle Disarticulation Amputation 356
21.17 ­Transtibial Amputation 357
21.18 ­Knee Disarticulation Amputation 359
21.19 ­Transfemoral Amputation 359
21.20 ­Conclusions 360
­ References 360

22 Rehabilitation of the Amputee 363

Karen Kowalske and Merrine Klakeel
22.1 ­Lower Limb Amputation and Prosthetics 363
22.2 ­Foot Amputations 364
22.3 ­Foot Orthotics 365
22.4 ­Transtibial Amputations 366
22.5 ­Ankle/Foot Components 369
22.6 ­Conclusion 372
­ References 372

23 Surgery for the Diabetic Foot: Prophylactic and Osteomyelitis

Surgery – Is there an Evidence Base? 375
Javier Aragón-Sánchez
23.1 ­The Role of Surgery Preventing Occurrence and Recurrence of Foot Ulcers 376
23.2 ­Preoperative Care 376
23.3 ­Hallux and First Metatarsal Head Procedures 377
23.4 ­Lesser Toes 380
23.5 ­Lesser Metatarsal Heads 381
 Contents xiii

23.6 ­ endon Achilles Lengthening 383

T
23.7 ­Curative Surgery for Treating Diabetic Foot Osteomyelitis 385
23.8 ­Surgery of Forefoot Osteomyelitis 386
23.9 ­Surgery of Midfoot Osteomyelitis 388
23.10 ­Surgery of Rear Foot Osteomyelitis 388
­ References 389

24 Footwear and Orthoses for People with Diabetes 395

J.S. Ulbrecht and S.A. Bus
24.1 ­Introduction 395
24.2 ­What is a Therapeutic Shoe for a Person Living with Diabetes? 395
24.3 ­Who Needs Therapeutic Shoes? 402
24.4 ­Choosing the Appropriate Footwear for the Patient with LOPS 403
24.5 ­Summary and Future Trends 406
­References 406

25 The Diabetic Foot in Remission 409

Tanzim Khan, Sicco A. Bus, Andrew J.M. Boulton, and David G. Armstrong
25.1 ­The Diabetic Foot in Remission 409
25.2 ­Maintaining Remission 410
25.3 ­Conclusion 413
­References 414

26 Setting up a Diabetic Foot Clinic 417

Michael E. Edmonds and N.L. Petrova
26.1 ­Natural History of the Diabetic Foot 417
26.2 ­Principles of Care of the Diabetic Foot 418
26.3 ­Space for the Diabetic Foot Clinic 418
26.4 ­Personnel for the Diabetic Foot Clinic 419
26.5 ­Organisation of the Diabetic Foot Clinic 422
26.6 ­Conclusion 426
­References 426

27 National Audit of Diabetic Foot Care: Continuing Audit Is Essential

for the Delivery of Optimal Care of Diabetic Foot Ulcers 429
William Jeffcoate, Gerry Rayman, and Bob Young
27.1 ­Why Should We Document the Outcome of Routine Care? 429
27.2 ­General Principles of Clinical Audit 430
27.3 ­National Diabetes Foot Care Audit of England and Wales 433
­ References 437

28 Regenerative Medicine and the Diabetic Foot 439

Zachary A. Stern-Buchbinder, Babak Hajhosseini, and Geoffrey C. Gurtner
28.1 ­Introduction 439
28.2 ­Stem Cells 439
28.3 ­Diabetes and Healing Impairment 442
28.4 ­Diabetes and Vascular Dysfunction 443
xiv Contents

28.5 ­ unctional Heterogeneity of Stem Cells 446

F
28.6 ­Advances in Regenerative Therapy 447
28.7 ­Conclusion 449
­References 449

29 Role of the Plastic Surgeon in Diabetic Foot Care 457

Joon Pio (Jp) Hong and Hyunsuk Peter Suh
29.1 ­Introduction 457
29.2 ­Multidisciplinary Approach and the Spectrum of Care 458
29.3 ­Reconstruction Algorithm 459
29.4 ­Debridement (this Is Covered in Detail in another Chapter) 460
29.5 ­Evaluating and Enhancing the Vascular Status 461
29.6 ­Skin Grafts and Substitutes 462
29.7 ­Local Flaps 463
29.8 ­Free Flaps 464
29.9 ­Amputation 466
29.10 ­Conclusion 467
­References 469

30a Algorithms for Diabetic Foot Care: Management of the Hot Swollen Foot 473
Michael E. Edmonds, Chris Manu, and Nina Petrova
­References 480

30b Approach to a New Diabetic Foot Ulceration 481

Prashanth R.J. Vas and Michael E. Edmonds
30b.1 ­Introduction 481
30b.2 ­Clinical Care for the Management of DFU 482
30b.3 ­Management of DFU 485
30b.4 ­Structural Care Process in DFU Management 490
­ References 491

30c Algorithms for Diabetic Foot Care: Vascular Evaluation 495

G. Dovell and R.J. Hinchliffe
30c.1 ­Introduction 495
30c.2 ­Methods of Vascular Evaluation – Detecting Peripheral Artery Disease 496
30c.3 ­Vascular Imaging 498
30c.4 ­Conclusions 500
­References 503

30d Algorithms for Diagnosis and Management of Infection in the Diabetic Foot 507
Edgar J.G. Peters and Benjamin A. Lipsky
30d.1 ­Diagnosis of Infection 507
30d.2 ­Therapy of Infection 509
­References 514

Index 515

List of Contributors
Caroline A. Abbott
Research Centre for Musculoskeletal
Science & Sports Medicine, Department
of Life Sciences, Faculty of Science &
Engineering, Manchester Metropolitan
University, Manchester, UK
Zulfiqarali G. Abbas
Internal Medicine, Abbas Medical Centre,
Muhimbili University of Health and Allied
Sciences, Dar es Salaam, Tanzania
David G. Armstrong
Southwestern Academic Limb Salvage
Alliance (SALSA), Department of Surgery,
Keck School of Medicine of University
of Southern California, Los Angeles, CA, USA
Samir H. Assaad-Khalil
Department of Internal Medicine, Unit
of Diabetology, Lipidology & Metabolism,
Diabetes Foot Care Centre, Faculty
of Medicine, Alexandria University,
Alexandria, Egypt
Abdul Basit
Baqai Institute of Diabetology and
Endocrinology, Baqai Medical University,
Karachi, Pakistan
Neal R. Barshes
Division of Vascular Surgery and
Endovascular Therapy,
Michael E. DeBakey Department of
Surgery, Houston, TX, USA
0004743209.INDD 15
xv
Andrew J.M. Boulton
University of Manchester, Manchester, UK;
Manchester Royal Infirmary,
Manchester, UK;
Diabetes Research Institute, University of
Miami, Miami, FL, USA
Edward J. Boyko
VA Puget Sound Healthcare System and
the University of Washington, Seattle,
WA, USA
S. A. Bus
Department of Rehabilitation Medicine,
Amsterdam UMC, University of
Amsterdam, Amsterdam, The Netherlands
Avneesh Chhabra
Radiology & Orthopedic Surgery,
University of Texas Southwestern Medical
Center, Dallas, TX, USA;
Adjunct faculty‐Johns Hopkins University,
Baltimore, MD, USA; Walton Centre of
Neurosciences, Manchester, UK
G. Dovell
Bristol Bath and Weston Vascular Network,
Bristol, UK;
Bristol Centre for Surgical Research,
University of Bristol, Bristol, UK
Michael E. Edmonds
Diabetic Foot Clinic, King’s College Hospital
NHS Foundation Trust, London, UK
3/20/2020 6:53:27 PM
xvi List of Contributors
Frances L. Game
University Hospitals of Derby and Burton
NHS Foundation Trust, Derby, UK
Norina Alinta Gâvan
Association for Podiatry, Cluj‐Napoca,
Romania
Geoffrey C. Gurtner
Division of Plastic & Reconstructive
Surgery, Department of Surgery, Stanford
University School of Medicine, Stanford,
CA, USA
R.J. Hinchliffe
Bristol Bath and Weston Vascular
Network, Bristol, UK;
Bristol Centre for Surgical Research,
University of Bristol, Bristol, UK
Joon Pio (Jp) Hong
Department of Plastic and Reconstructive
Surgery, Asan Medical Center, University
of Ulsan Collage of Medicine, Seoul, Korea
William J. Jeffcoate
Nottingham University Hospitals NHS
Trust, Nottingham, UK
Marion Kerr
Insight Health Economics, London, UK
Merrine Klakeel
University of Texas Southwestern Medical
Center, Dallas, TX, USA
Shigeo Kono
WHO-collaborating Centre for Diabetes
Treatment and Education, National
Hospital Organization, Kyoto Medical
Center, Japan
Karen Kowalske
University of Texas Southwestern Medical
Center, Dallas, TX, USA
Javier La Fontaine
Department of Orthopaedic Surgery and
Department of Plastic Surgery, University
of Texas Southwestern Medical Center,
Dallas, TX, USA
Lawrence Lavery
Department of Plastic Surgery, Orthopaedic
Surgery, and Physical Medicine &
Rehabilitation, University of Texas
Southwestern Medical Center, Dallas,
TX, USA
Peter A. Lazzarini
Allied Health Research Collaborative, The
Prince Charles Hospital, and
School of Clinical Sciences, Queensland
University of Technology, Brisbane,
Queensland, Australia
Benjamin A. Lipsky
Department of Medicine, University of
Washington, Seattle, WA USA;
Green Templeton College, University of
Oxford, Oxford, UK
George Liu
Department of Orthopaedic Surgery,
University of Texas Southwestern Medical
Center, Dallas, TX, USA
Joseph L. Mills
Division of Vascular Surgery and
Endovascular Therapy,
Michael E. DeBakey Department of
Surgery, Houston, TX, USA
Misaki M. Kiguchi
Department of Vascular Surgery,
MedStar Washington Hospital Center,
Washington, DC, USA
Matilde Monteiro-Soares
MEDCIDS and CINTESIS, Faculty of
Medicine, University of Porto, Porto,
Portugal

Bijan Najafi
Interdisciplinary Consortium for Advanced
Motion Performance (iCAMP), Division
of Vascular Surgery and Endovascular
Therapy, Michael E. DeBakey Department
of Surgery, Baylor College of Medicine,
Houston, TX, USA
Hermelinda C. Pedrosa
Brazilian Society of Diabetes – Government
Relations Advisor 2020-202, Endocrinology
Unit/FEPECS Research and Diabetic
Foot Center, Brasilia, Brazil; Worldwide
Initiatives for Diabetes Education
N.L. Petrova
Diabetic Foot Clinic, King’s College Hospital
NHS Foundation Trust, London, UK
Michael S. Pinzur
Orthopaedic Surgery, Loyola University
Health System, Maywood, IL, USA
Gerry Rayman
The Diabetes Centre, Ipswich Hospital
Ipswich, UK; University of East Anglia
Norwich, UK; University of Suffolk,
Ipswich, UK
Katherine M. Raspovic
Department of Orthopaedic Surgery and
Department of Plastic Surgery, University
of Texas Southwestern Medical Center,
Dallas, TX, USA
Neil D. Reeves
Research Centre for Musculoskeletal
Science and Sports Medicine, Department
of Life Sciences, Faculty of Science and
Engineering, Manchester Metropolitan
University, Manchester, UK
Javier Aragón-Sánchez
Surgery and Diabetic Foot Unit
Department
La Paloma Hospital
Las Palmas de Gran Canaria
Spain
List of Contributors xvii
Adam P. Schiff
Department of Orthopaedic Surgery,
Loyola University Medical Center,
Maywood, IL, USA
Dinesh Selvarajah
Senior Lecturer in Diabetes and Honorary
Consultant Physician
University of Sheffield, Sheffield, UK
Gordon Sloan
Clinical Research Fellow
University of Sheffield, Sheffield, UK
Hyunsuk Peter Suh
Department of Plastic and Reconstructive
Surgery, Asan Medical Center, University
of Ulsan Collage of Medicine, Seoul, Korea
Solomon Tesfaye
Consultant Diabetologist and Honorary
Professor of Diabetic Medicine, University
of Sheffield, Sheffield, UK
J.S. Ulbrecht
Department of BioBehavioral Health and
Medicine, Pennsylvania State University,
University Park, PA, USA;
Mount Nittany Health, State College,
PA, USA
Loretta Vileikyte
Department of Medicine, University of
Manchester, Manchester, UK;
Division of Endocrinology, Diabetes &
Metabolism, University of Miami, Miami,
FL, USA;
Dept of Dermatology, University of Miami,
Miami, FL, USA
M. Viswanathan
WHO Collaborating Centre for Research,
Education and Training in Diabetes,
Diabetes Research Centre and
M.V. Hospital for Diabetes, Royapuram,
Chennai, Tamilnadu, India
xviii List of Contributors

Richard William Whitehouse Dane K. Wukich

Manchester Royal Infirmary, Manchester Department of Orthopaedic Surgery,
University Hospitals Foundation NHS University of Texas Southwestern Medical
Trust, Manchester, UK Center, Dallas, TX, USA

Edward Y. Woo Bob Young

Department of Vascular Surgery, MedStar Diabetes UK, London, UK
Washington Hospital Center, Washington,
DC, USA
 xix

Preface

Much progress has been made in the diagnosis and management of diabetic foot problems
since the first edition of this book was published more than three decades ago in 1987. The
foot is no longer the “Cinderella” of the late complications of diabetes, and in many areas
one could say that the era of anecdote has progressed to the era of evidence‐based
practice.
As in the previous editions, we have attempted to provide a concise clinical text, and a
number of new topics are included since the 4th edition was published in 2006. These
include a global review of diabetic foot problems, new imagining techniques, smart tech-
nology, and the use of regenerative medicine and finally providing algorithms for diabetic
foot care.
Any medical textbook is necessarily out of date at the time of publication and this cer-
tainly includes the diabetic foot. However, in view of a number of key randomized con-
trolled trials that have been published since 2018, these will receive a brief coverage in the
Introduction.
We sincerely hope that you find this clinical text of benefit in the management of patients
with diabetic foot problems.
Andrew J.M. Boulton
Gerry Rayman
Dane K. Wukich
 xxi

Introduction

Our good friend and author of several contributions in this book, Professor Michael
Edmonds, wrote an editorial in 2018 entitled, ‘A renaissance in diabetic foot care: new
­evidence‐based treatments’ [1]. This renaissance is ongoing, so it was felt that reference
should be made to some of the key developments that might not be covered elsewhere in
this book. Included in this brief overview will be new evidence‐based therapies including
topical therapies and oxygen‐based treatments, infection management, and smart
technologies.
A number of well designed, randomised controlled trials (RCTs) were published in 2018.
The first proven treatment for neuro‐ischaemic diabetic foot ulcers, sucrose octasulphate
dressings, was reported in the Explorer study [2]. In the active group, 48% of wounds were
closed after 20 weeks compared to 30% in the control dressing group (p<0.002). In the same
journal, Lancet Diabetes Endocrinology, Game and colleagues reported the positive effect of
the LeucoPatch device (a disc containing autologous platelets, leucocytes, and fibrin) when
applied to the surface of hard‐to‐heal foot ulcers [3]. The addition of a nitric oxide ­generating
medical device to a wound dressing has also been shown to improve healing in an RCT [4].
There has been increasing interest in the use of oxygen‐based therapies in wound healing
in recent years. Whereas the latest studies of hyperbaric oxygen have been negative [5,6],
there have been interesting developments in the use of devices delivering topical oxygen.
There is now evidence that both continuous [7] and cyclical [8] topical wound oxygen
­therapy may improve wound healing rates.
There has also been a significant increase in studies using placental derived wound
­products which show promising results but are limited by being unblinded and/or subject
to other biases, and the availability and use of these products outside the USA is limited. If
high quality RCTs confirm benefit, the widespread availability of placental tissue, and the
possibility of less expensive processing methods could make this a cost effective treatment
with applicability in lower economy countries [9,10].
In the field of infected foot ulcers, many were surprised to read the result of the OVIVA
study [11] which randomized patients with osteomyelitis to oral vs. intravenous antibiotics
and showed no superiority of either delivery modality. These observations will certainly
challenge the approach to osteomyelitis management in the future. A detailed update
review on infection management has been published by the American Diabetes Association
in 2020 [12].
xxii Introduction

Lastly, the area of smart technology in the diabetic foot is progressing rapidly. The effi-
cacy of smart mat technology to predict foot ulceration by monitoring temperature differ-
ences between the two feet has been confirmed [13], and RCTs are underway in this area.
Similarly, in the field of pressure measurement, an intelligent insole system has been
shown to reduce foot ulcer recurrence at plantar sites [14].
These are surely exciting times in the prevention and treatment of diabetic foot problems
and we firmly believe that this new decade will bring many more developments in this
rapidly expanding area.
Andrew J.M. Boulton
Gerry Rayman
Dane K. Wukich

R
­ eferences

1 Edmonds, M.E. (2018). A renaissance in diabetic foot care: new evidence‐based treatments.
Lancet Diabet. Endocrinol. 6: 837–838.
2 Edmonds, M., Lázaro‐Martínez, J.L., Alfayate‐Garcia, J.M. et al. (2018). Sucrose octasulfate
dressing versus control dressing in patients with neuroischemic diabetic foot ulcers
(Explorer): an international, multicentre, double‐blind, randomized controlled trial. Lancet
Diabetes Endocrinol. 6: 186–196.
3 Game, F., Jeffcoate, W., Tarnow, L. et al. (2018). LeucoPatch system for the management of
hard‐to‐heal diabetic foot ulcers in the UK, Denmark, and Sweden: an observer‐masked,
randomized controlled trial. Lancet Diabetes Endocrinol. 6: 870–878.
4 Edmonds, M.E., Bodansky, H.J., Boulton, A.J.M. et al. (2018). Multicentre, randomized
controlled, observer‐blinded study of a nitric oxide generating treatment in foot ulcers of
patients with diabetes: ProNox1 study. Wound Rep. Regen. 26: 228–237.
5 Santema, K.T.B., Stoekenbroek, R.M., Koelemay, M.J.W. et al. (2018). Hyperbaric oxygen
therapy in the treatment of ischaemic lower‐extremity ulcers in patients with diabetes:
results of the DAMO2CLES multicentre randomized controlled trial. Diabetes Care 41:
112–119.
6 Löndahl, M. and Boulton, A.J.M. (2020) Hyperbaric oxygen: useless or useful? A debate.
Diab. Metab. Res. Rev. 2020 (in press).
7 Niederauer, M.Q., Michalek, J.E., Liu, Q. et al. (2018). Continuous diffusion of oxygen
improves diabetic foot ulcer healing when compared with a placebo control: a randomized,
double‐blind, multicentre study. J. Wound Care 27 (suppl 9): S30–S45.
8 Frykberg, R.G., Franks, P.J., Edmonds, M. et al. (2019). A multinational, multicentre,
randomized, double‐blinded, placebo‐controlled trial to evaluate the efficacy of cyclical
topical wound oxygen therapy (TWO2) in the treatment of chronic diabetic foot ulcers: the
TWO2 study. Diabetes Care 2019, Oct 16, Epub ahead of print.
9 Ananian, C.E., Dhillon, Y.S., Van Gils, C.C. et al. (2018). A multicenter, randomized,
single‐blind trial comparing the efficacy of viable cryopreserved placental membrane to
human fibroblast‐derived dermal substitute for the treatment of chronic diabetic foot ulcers.
Wound Repair Regen. 26: 274–83.
 Introduction xxiii

10 Tettelbach, W., Cazzell, S., Sigal, F. et al. (2019). A multicentre prospective randomised
controlled comparative parallel study of dehydrated human umbilical cord (EpiCord)
allograft for the treatment of diabetic foot ulcers. Int. Wound J. 16: 122–30.
11 Li, H.K., Rombach, I., Zambellas, R. et al. (2019). OVIVA Trial Collaborators. Oral versus
intravenous antibiotics for bone and joint infection. N. Engl. J. Med. 380: 425–436.
12 Boulton, A.J.M., Armstrong, D.G., Hardman, M.J. et al. (2020). Diagnosis and management
of diabetic foot infections. Arlington (VA). American Diabetes Association.
13 Frykberg, R.G., Gordon, I., Rayzelman, A.M. et al. (2017). Feasibility and efficacy of a
smart mat technology to predict development of diabetic plantar ulcers. Diabetes Care 40:
973–980.
14 Abbott, C.A., Chatwin, K.E., Foden, P. et al. (2019). Innovative intelligent insole system
reduces diabetic foot ulcer recurrence at plantar sites: prospective, randomized proof‐of‐
concept study. Lancet Digital Health 1: e308–318.
 1

Epidemiology and Economic Impact of Foot Ulcers

Edward J. Boyko1 and Matilde Monteiro-Soares2
1
VA Puget Sound Healthcare System and the University of Washington, Seattle, WA, USA
2
MEDCIDS and CINTESIS, Faculty of Medicine, University of Porto, Porto, Portugal

1.1 ­Introduction

Diabetes mellitus accounts for the majority of nontraumatic lower limb amputations [1],
despite affecting a minority (9.4%) of the U.S. population [2]. A systematic review of risk of
lower limb amputation in persons with and without diabetes in a defined population
yielded 19 publications reporting results from Europe, UK and the US with relative risk of
amputation in diabetes ranging from 7.4 to 41.3 [3]. Notably this range of relative risks for
amputation exceeds that for diabetes and fatal coronary heart disease of 3.5 (women) and
2.1 (men) from a meta‐analysis of 37 prospective studies [4], and is of similar magnitude to
that seen for the association between ever smoking and lung cancer [5]. The chief anteced-
ent to diabetic lower limb amputation is the nonhealing foot ulcer [6], which precedes
approximately 80% of diabetic amputations, and which has been reported to lead to ampu-
tation in 15% of cases [7–9]. The problem of higher amputation risk in diabetes can be
traced backwards in the causal chain of events to the development of a diabetic foot ulcer
(DFU) [6].

1.2 ­Diabetic Foot Ulcer (DFU) Definition

Diabetic Foot Ulcer (DFU) is defined as a full thickness skin defect below the ankle that is
slow to heal or non‐healing. Amongst 1000 patients with DFU enrolled in the Eurodiale
Study and followed for up to one year, median time to healing was 147 days for toe (95% CI
135–159 days), 188 days for midfoot (95% CI 158–218 days) and 237 days for heel ulcers (95%
CI 205–269 days) [10], with healing success at one year of 79% for plantar and 73% for non‐
plantar ulcers. The available data demonstrate prolonged healing times for DFU and the
frequent occurrence of healing failure.
The study of the epidemiology of DFU or any health condition requires a case definition
to identify afflicted persons. There is no established case definition for DFU in general use.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
2 1 Epidemiology and Economic Impact of Foot Ulcers

Definitions of DFU in the published literature may include features such as full thickness
skin defect distal to the malleoli, but in some reports no case definition is provided with the
identification of DFUs left to the judgement of foot care providers; or through review of
podiatry records or electronic medical record data. Although delayed healing is a recog-
nized feature of DFU, there is no established criterion for ‘slow to heal’ and rarely is a dura-
tion criterion included in the ulcer definition. The Seattle Diabetic Foot Study required a
healing time greater than 14 days to meet the criteria for a DFU [11], whilst a clinical trial
of custom footwear specifically mentioned that duration of ulceration was not be taken
into consideration [12]. Consensus on a DFU definition would enable comparisons of the
frequency of this complication across populations, regions, and over time.

1.3 ­DFU Classification

DFU classification systems function as a guide to the best treatment and as a predictor of
the probability of wound healing and the need for amputation. The typical components of
a wound classification system include wound depth, presence and severity of infection,
gangrene, and ischemia. A systematic review of DFU classification systems identified 15
such systems reported in 25 articles [13]. Examples of the systems for which the greatest
number of validation studies have been performed are the Meggitt‐Wagner (9 validations),
and the University of Texas and S(AD)SAD systems (5 validations each). Features of these
three systems are seen in Table 1.1.
Comparisons of the ability of different classification systems have generally found them
to be predictive of healing and amputation [14, 15].
Little research has been conducted comparing these classification systems using methods
commonly employed for other diagnostic modalities such as comparison of area under
receiver operating characteristic curves (AUROC), or by comparing test characteristics that
alter pre‐test probability, such as likelihood ratios [16, 17]. Jeon et al. compared five different
DFU classification systems on the ability to predict amputation [18] that included the systems
shown in Table 1.1, except that a simplified version of the S(AD)SAD system was used (SINBAD).
All systems showed excellent ability to predict amputation with AUROC ranging from 0.85 to
0.89, and positive and negative likelihood ratios ranging from 4 to 18 and 0.21 to 0.41, respec-
tively. Monteiro‐Soares et al. compared 11 different prediction models for lower limb amputa-
tion in a prospective study of 293 patients with DFU and found positive and negative likelihood
ratios ranging from 1.0 to 5.9, and 0.1 to 0.9, respectively, and AUROC curves ranging from
0.53 to 0.83, indicating that considerable diversity exists with some models showing signifi-
cantly poorer prediction performance [19]. Further research is needed comparing existing
classification systems to predict healing and amputation in patients with DFU.
DFUs are often described without using a classification system, but in reference to likely
ulcer aetiology (neuropathic versus ischemic versus both) or foot location [20]. Ulcers usu-
ally develop over bony prominences that can be found on the plantar and dorsal foot sur-
faces especially if a structural deformity has developed resulting in abnormally high arch,
prominent metatarsal heads, and clawing of the toes. The most common location for ulcer
in the Eurodiale Study was on toes, with nearly equal division between plantar and non‐
plantar surfaces. Ulcers on the heel took longer and were less likely overall to re‐­epithelialize
 1.4 ­DFU Incidence and Prevalenc 3

Table 1.1 Diabetic foot ulcer wound classification systems.

Wagner

Stage
1 Superficial ulcer of skin or subcutaneous tissue
2 Ulcers extend into tendon, bone, or capsule
3 Deep ulcer with osteomyelitis, or abscess
4 Gangrene of toes or forefoot
5 Midfoot or hindfoot gangrene

University of Texas

Wound description No infection Infection present Ischemia present Infection and

or ischemia ischemia present
Superficial 1A 1B 1C 1D
Penetrates to tendon 2A 2B 2C 2D
or capsule
Penetrates to bone or 3A 3B 3C 3D
joint

S(AD)SAD – Size (Area, Depth), Sepsis, Arteriopathy, Denervation

SIZE
Grade Area Depth Sepsis Arterial disease Neuropathy
0 Skin Skin intact None Pulses present Pin prick intact
intact
1 < 1 cm2 Skin and Surface Pulses Pin prick reduced
subcutaneous diminished or
one missing
2 1–3 cm2 Tendon, joint Cellulitis Absence of pedal Pin prick absent
pulses
3 > 3 cm2 Bone, joint Osteomyelitis Gangrene Charcot
space deformity

than other foot locations, but no difference was observed in overall healing success com-
paring plantar to non‐plantar locations [10]. Similar healing success was seen amongst 405
patients with a neuropathic ulcer in plantar (n = 175, 91% healed) and non‐plantar
(n = 230, 94% healed) locations [21].

1.4 ­DFU Incidence and Prevalence

A wide range of estimates is available for DFU incidence and prevalence. A recent system-
atic review of the global literature identified 67 publications from 33 different countries
and 5 continents [22]. Foot ulcer prevalence ranged from 1.5 to 16.6% in populations that
4 1 Epidemiology and Economic Impact of Foot Ulcers

included inpatients, outpatients, diabetes clinics, and defined communities. Identification

of foot ulcers was based on self‐report, examination, medical record review, or electronic
diagnostic codes (ICD‐9). The report highlights the difficulties in assessing the frequency
of this complication worldwide given the inconsistent methodologies employed.
The capture of this complication in a large population or nationally requires use of elec-
tronic diagnostic codes. The value of this information depends on the completeness and
accuracy of such codes. The sensitivity and specificity of five such methods were recently
estimated by comparison to medical record reviews of 512 patients receiving outpatient
and inpatient care in the US from the Veterans Health Administration [23]. Sensitivity of
all methods was at least 93%, with specificity ranging from 74 to 91%.
Several reviews of large, well‐defined populations have been published on the incidence
and prevalence of DFU. The Translating Research Into Action for Diabetes (TRIAD)
included a random sample of adults with diabetes enrolled in 10 managed care health
plans in eight US States that served approximately 180 000 persons with diabetes [24]. Foot
ulcer was defined by ICD‐9‐CM code 707.1x or 707.9 in any inpatient or outpatient
encounter. Between 1999 and 2003, 205 patients had at least one DFU (2.9%). A search of
electronic health data in diabetic patients 67 years or older receiving care in the US from
Veterans Health Administration and Medicare in 1999 identified a lower extremity ulcer
or infection prevalence of 13% [25]. A more recent survey of outpatient and inpatient
ICD‐9 diagnosis codes in national US Medicare fee for service data from 2006 to 2008
revealed a prevalence of 8.0–8.1% and an annual incidence of 6.0% of DFU [26, 27]. A
broad range of diagnosis codes were used to define DFU including lower limb ulceration
(707), cellulitis (682), osteomyelitis (730), and open wounds (892), but excluding venous
leg ulcer (454).
More recent evidence suggests that DFU incidence is declining in several developed
countries. In a review of electronic patient records, the incidence in persons with both type
1 and 2 diabetes dropped between 2002 and 2014 at a large specialized diabetes hospital in
Denmark, 8.1 per 1000 patient‐years to 2.6 per 1000 patient‐years, and 17.0 per 1000 patient‐
years to 8.7 per 1000 patient‐years, respectively [28]. The incidence of foot ulcer in a pri-
mary care practice database in the Netherlands that included over 1.5 million patients from
about 500 practices was 0.34% between 2010 and 2013 [29], considerably lower than an
incidence ranging from 1.2 to 3.0% in an earlier Dutch study in a primary care practice from
1993 to 1998 [30]. The U.S. Diabetes Surveillance System maintained by the Division of
Diabetes Translation at the Centres for Disease Control and Prevention provides estimates
over time of the incidence of diabetes and its complications. Figure 1.1 displays the trend
over time in hospitalization for lower extremity ulcer, inflammation, or infection. The U.S.
National Inpatient Sample (NIS) that includes data from more than seven million hospital
stays per year was searched for lower limb ICD‐9 codes in persons with diabetes, including
ulcer (707), carbuncle (680), cellulitis (681–682), pyogenic arthritis (711), osteomyelitis
(730), gangrene (785), and venous ulcer (454). The trend since 1993 shows a fall in the age‐
adjusted hospitalization rate for this composite outcome when first‐listed, with perhaps a
levelling‐off since 2009, whilst the trend for any‐listed outcome is less clear. Given the broad
definition of the outcome, whether the figure reflects a fall in hospitalizations for first‐listed
ulceration or the other conditions included in the outcome is not known. When assessing
whether a change in incidence has occurred, it is important to consider that a decline might
 1.5 ­DFU Recurrenc 5

First-Listed Ulcer/Inflammation/Infection (Ulcer)

30
Any-Listed Ulcer/Inflammation/Infection (Ulcer)

25
Rate per 1,000

20

15

10

0
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
Rate per 1,000 (Total)

Figure 1.1 Age-adjusted hospitalization rate per 1000 for lower extremity ulcer, inflammation, or
infection among the United States diabetic population, including all ages.

be due not only to fewer ulcers occurring but also enlargement of the denominator, which
might occur due to improvements in diabetes screening and case detection.
Given the evidence that the rate of foot ulceration may be on the decline in some devel-
oped countries, it may no longer be the case that the estimated cumulative lifetime DFU risk
is 15–25% [31].

1.5 ­DFU Recurrence

The epidemiology of DFU clearly demonstrates that it is not an isolated occurrence, as

approximately 40% develop recurrent ulceration within one year after healing [32]. This
fact supports the opinion that patients with DFU who heal should be viewed as being in
remission from active ulceration and not cured. What is not clear from the literature on
ulcer recurrence is whether the new ulcer is at the healed site or a new location. A study
based in Malta specifically addressed the location of recurrent DFU [33]. Of 66 diabetic
patients presenting with ulcer, 32 presented with a recurrent ulcer, with 27 (84%) experi-
encing the recurrence on the same foot, and 11 (34%) presenting at the same site as the
previous ulcer. Although this is a small study, it suggests that the majority of recurrent
DFUs develop at a site different from the original ulcer. A recently published study from
Egypt of 93 diabetic patients with a healed foot ulcer who were followed for two years
noted a recurrence in 61%, with 67% of recurrences in the same foot, and 37% of recur-
rences at the previous healed ulcer site, therefore supporting the results of the Malta study
that recurrences were more likely to be located at sites other than that of the healed ulcer
[34]. Given that most ‘recurrences’ are actually ulcers in different locations and not at the
site of the previously healed ulcer, the problem of recurrence is more likely due to the same
factors that led to the initial ulcer than defective wound re‐epithelialization.
6 1 Epidemiology and Economic Impact of Foot Ulcers

1.6 ­Risk Factors for Diabetic Foot Ulcers and Lower

Extremity Amputation

A number of investigators have examined risk factors for DFU development or recur-
rence. The most commonly identified factors associated with higher risk of DFU develop-
ment are diabetic peripheral neuropathy, peripheral arterial disease (PAD), foot deformity
and previous foot complications. These variables were consistently associated with DFU
development [35].
There are several classifications that can be used to stratify subjects by their risk of devel-
oping a DFU. At least five classification systems exist, with different structures, but that
most commonly include diabetic peripheral neuropathy, foot deformity, PAD, and previous
DFU or lower extremity amputation (LEA) [36]. These classifications presented similar
prognostic accuracy when validated in the same cohort [36, 37].
In a cohort of subjects with healed DFU from the Eurodiale consortium, independent
predictors of DFU recurrence were initial DFU plantar location, presence of osteomyeli-
tis, glycated haemoglobin greater than 7.5%, and C‐reactive protein greater than 5 mg/l [38].
In investigations of clinical tests that can help predict DFU healing, only transcutane-
ous oxygen measurement and ankle brachial index (ABI) proved of benefit [39].
Higher minor LEA risk was linked with male sex, greater DFU depth, presence of infec-
tion, and PAD in the Eurodiale consortium study [40]. Hypertension, ischemic heart dis-
ease, cerebrovascular disease, and PAD were found to be associated with higher major
LEA rate [41]. In addition to these factors, different systematic reviews, including from 7 to
101 studies, concluded that being male [42, 43], smoking [43] and presence of depression
[44] increased the risk of LEA. Regarding laboratory findings, higher fasting blood glucose,
white blood cell count, C‐reactive protein, and erythrocyte sedimentation rate were predis-
posing factors for LEA [45]. Two reviews concluded that the risk of LEA increased with
higher glycated haemoglobin levels [45, 46]. A systematic review found that intensive gly-
caemic control significantly decreased the risk of LEA and sensory vibration perception
impairment [47].
Self‐care practices were also related to risk of both DFU and LEA. In a study, when the
general practitioner indicated in the health registry he/she had good influence of the
patient’s own effort in diabetes treatment and that the patient had very good motivation for
diabetes management, it was associated with a lower risk of both DFU and LEA during six
years of follow up [48].
There are at least 16 classification systems that can be used for DFU prognosis assess-
ment/LEA prediction [13, 49]. The Meggitt–Wagner, S(AD)SAD and Texas University
Classification systems were the most extensively validated. When comparing all the sys-
tems they presented similar accuracy values [19, 49]. The most commonly included varia-
bles were DFU’s area, depth and infection and presence of PAD, diabetic peripheral
neuropathy, and foot deformity.
A systematic review [50] reported that, in subjects with DM, the most common risk fac-
tors associated with a higher risk of death were being older, male, with nephropathy, DFU
and/or LEA presence or history, PAD, longer diabetes duration, and poor glycaemic con-
trol. However, results were not consistent across studies. In a study from Thailand [51],
including subjects with and without DFU, DFU history, type 1 diabetes, high low‐density
 1.7 ­Diabetic Foot Ulcer Outcome 7

lipoprotein, and being male was linked to a higher risk of mortality. One study, conducted
in Brazil, concluded that the risk of dying after a DFU was increased in older people, and
in those with low haemoglobin values and a major LEA [52].
In veterans following DFU development, an increased risk of mortality was observed in
older, male, married subjects, with peripheral neuropathy, coronary heart disease, PAD,
history of stroke, foot deformity, nephropathy, gangrene and osteomyelitis, more outpa-
tient or emergency room visits, more hospitalizations, and absence of statin use at baseline
[53]. In the Eurodiale study, health‐related quality of life (HRQoL) low global and domain
specific values, measured by the EQ‐5D, were highly associated with risk of dying [54]. In
the same way, identity (How much do you experience symptoms?) and coherence (How
well do you feel you understand your ulcer?) beliefs had a significant impact on mortality
in another study [55].

1.7 ­Diabetic Foot Ulcer Outcomes

1.7.1 Health Centred Outcomes

In a systematic review assessing predictive factors for DFU occurrence, DFU development
(including exclusively patients with no active, recently healed or past DFU history) ranged
from 5.0 (after a mean follow up of 43 months) to 7.2% (after a mean follow up of 12 months)
and recurrence from 15.5 to 60.5%, after a mean follow up of 24 and 32 months [35]. In
Denmark, after six years of DM diagnosis, 2.93% of the individuals developed their first
DFU [48].
In a cohort of subjects with a healed plantar forefoot DFU, 42% had another DFU over
two years of follow‐up [56]. During a three year follow‐up, 57.5% of subjects with a healed
DFU recurred in the Eurodiale cohort [38]. In a cohort of individuals with a minor LEA
history (defined as below the ankle), re‐ulceration‐free survival time was merely eight
months after LEA [57].
In one study, 30 days after a hospitalization for treatment of a DFU, 21.5% of individuals
required a re‐admission. The majority of the re‐admissions were unplanned (81.8%) and
related to the wound and vascular status (67.7%) [58]. In a retrospective cohort study from
Brazil, conducted between 2007 and 2012, after a hospitalization, in a vascular surgery
unit, for treatment of DFUs and/or infections, 21% of patients were readmitted once and
18% two or more times [59].
LEA incidence and prevalence is highly variable. In England, one study reported that it
could vary 10‐fold for both minor (0.22–2.20 per 1000 person‐years) and major LEA (0.30–
3.25 per 1000 person‐years) [60]. The Eurodiale consortium observed that the minor LEA
rate in people with an active DFU, treated in 14 European Centres in 2003 and 2004, at one
year of follow‐up, ranged from 2.4 to 34% in the different centres [40]. A review assessing
the global variability of annual LEA incidence reported that it ranged from 46.1 to 9600 per
105 persons [61]. Major LEA varied from 5.6 to 600 per 105 individuals [61].
Having a DFU and/or LEA, especially major, are linked with remarkably high mortality
rates. A 2.4‐fold higher risk of death amongst patients with DFU was first reported in 1996
[62]. One study concluded that having a DFU significantly increased the mortality risk, inde-
8 1 Epidemiology and Economic Impact of Foot Ulcers

pendently of age and number of diabetes‐related complications [63]. These results are in line
with the ones reported in the largest cohort conducted until now evaluating the association
between DFU and death in individuals with DM [64]. The higher risk of dying in people with
DFU was addressed in several studies. A meta‐analysis showed higher pooled relative risk of
all‐cause mortality and of fatal myocardial infarction for those subjects that had a DFU [65].
This higher risk was also reported for Asian patients [51]. Subjects with a neuropathic DFU
may have a greater risk of dying due to ischemic heart disease [66]. These results were not
substantiated by other studies for which no differences in mortality were found [67].
Survival rates after an incident DFU were reported to be as low as 69% at 2 years and 29%
at 5 years [53]. One systematic review concluded that the five‐year mortality rate after a
DFU was around 40%, rising to 63% if the limb was amputated [50]. In another systematic
review, authors reported a five‐year mortality rate that varied from 53 to 100% in subjects
with a previous LEA [68]. In a more recent cohort of patients with a minor or major LEA
[67], survival rates at three and five years were 78 and 44% respectively. The median sur-
vival was 50 months. This value is comparable to those with a metastatic cancer. In subjects
with a cardiovascular event history median survival dropped to 40 months and in those
with nephropathy to 27 months.

1.7.2 Patient Centred Outcomes

Diabetic foot disease has an immense impact on patients’ lives by causing pain, impaired
mobility, limited social activities, and interference with relationships. However, when it
comes to patient‐centred outcomes, available evidence is still very scarce.
In 2012, a systematic review [69] was conducted to ascertain the value of patient‐reported
outcome measures to assess HRQoL. The SF‐36 was the most commonly used tool for
­quality of life (QoL) assessment, although several diabetic foot disease specific tools exist,
such as the Diabetic Foot Scale, NeuroQoL, and Norfolk QoL‐DN. HRQoL values were
lower in subjects with diabetes when compared to healthy subjects, but even lower when
foot ­disease occurs. When a DFU healed, HRQoL values improved. However, HRQoL
­values in subjects with an active DFU were lower than those reported by individuals after
a successful minor LEA. Another systematic review [70] that included research from
Spain, Italy, France, England, and Germany identified only six studies assessing QoL in
individuals with several diabetic foot complications (namely, foot ulcers, and amputa-
tions). Subjects with DFU presented a lower mean score on all SF‐36 domains, but particu-
larly in physical capacity. Those with non‐healed and recurrent DFU presented lower
values than those with healed DFU, and those that underwent a LEA reported lower values
when compared to those that did not.
The Eurodiale consortium stated that individuals with active DFU reported low EQ‐5D
values, with the mobility and pain/discomfort domains the most affected [54]. The inability
to stand or walk without help was considered the most important predictor of diminished
QoL. Using propensity score matching techniques, investigators found that there were no
differences in HRQoL between individuals with active DFU being treated conservatively
compared to those undergoing minor LEA [71]. A multi‐hospital study of the QoL of
Portuguese patients with diabetic foot concluded that, in subjects undergoing a LEA,
HRQoL after surgery could be predicted by HRQoL before surgery, the number of diabetes
 1.8 ­Economic Consideration 9

complications, and a previous LEA [72]. Although physical function HRQoL values dimin-
ished after surgery, no changes were found in the mental domain. Physical function HRQoL
after LEA was predicted by pain, having a first LEA, depression symptoms, and functional-
ity (measured using the Barthel Index) [73]. Mental HRQoL predictors were anxiety,
depression symptoms, and functionality.
Another study [74] concluded that amongst individuals with diabetic foot pathology, hav-
ing a LEA is the most feared diabetes‐related complication, surpassing blindness, infection,
dialysis, or even death. However, these results were different in subjects without diabetic
foot pathology who ranked their fear for this specific complication after blindness and death.

1.8 ­Economic Considerations

Diabetic foot complications represent a major burden for healthcare systems, due to both
direct and indirect costs. For example, from 2006 to 2010 and according to national emer-
gency department discharge data from the Agency for Healthcare Research and Quality
(AHRQ) Healthcare Cost and Utilization Project (HCUP) Nationwide Emergency
Department Sample (NEDS), more than 1 million cases of diabetic foot complications pre-
sented to emergency departments in the United States of America, incurring estimated
costs of 1.9 billion US$ per year [75].
In Brazil, it was estimated that the annual direct medical costs of diabetic foot disease in
2014 was 361 million Int$ (International Dollars) [76]. In 2001, in the United Kingdom
(UK) the estimated total costs were 509 million € and in Germany 551 € per patient to
manage diabetic foot complications [70]. In 2010–2011, the estimated cost in the UK
increased to 580 million € [77]. More than half of this amount was spent on DFU care
conducted in primary care and community settings. In Canada, DFU related care was
estimated at 547 million $ in 2011 [78].
Treatment of DFU generates excess cost when compared to the treatment of people with-
out DFU, with such costs persisting beyond the time of ulcer healing and showing high
variability. Attributable cost of DFU care, during the two years after diagnosis, amounted
to 28 000 US$ [9]. Greater DFU severity leads to higher cost of care and more proximal LEA
associated with greater costs compared to a minor LEA. One study reported that the mean
healthcare cost per patient with an active DFU without hospitalization is 730 €, increasing
to 2260 € when hospitalization is required [79]. Individuals with a DFU treated in the out-
patient setting represented a mean cost per month that ranged from 582 €, for those classi-
fied as Wagner grade 1, up to 742 €, for those classified as Wagner grade 4/5. Hospitalization
increased these amounts to 735 € and 3590 €, respectively. Other estimates are available
from a study in Russia, where treating a patient admitted due to a DFU categorized by
Wagner grade generated the following mean costs: grade 1–2450 €, grade 2–2821 €, grade
3–3937 €, and grade 4–5340 € [80]. Length of hospital stay, foot surgery, and vascular
­surgery were the variables having the greatest impact on cost escalation.
Costs of treatment of DFU based on a different wound classification system have also
been reported. An Austrian study [81] reported the average cost to heal a DFU categorized
according to the San Antonio Wound Classification as follows: stage A – 1071 € (no infection
or PAD), stage B – 5093 € (with PAD), stage C – 3467 € (infected DFU) and stage D – 7844 €
10 1 Epidemiology and Economic Impact of Foot Ulcers

(infected DFU with PAD). Also, in this study, undergoing a major LEA precipitously
increased the range of the costs of care. For example, a DFU classified as grade B may gener-
ate treatment costs ranging from 213 € to 29 585 € for those leading to a major LEA, a grade
C DFU from 55 to 8000 € to 22 498 €, and a grade D DFU from 5550 € to 13 900 €. In the
Eurodiale consortium study [82], costs ranged from 4214 € for a stage A DFU, up to 16 835 €
for a stage D DFU. In the same way, a healed DFU cost 7722 €, a non‐healed DFU after
12 months of care cost 20 064 €, and a major LEA 25 222 €.
The role of infection with regard to affecting costs of care was assessed in one UK inves-
tigation, where the estimated cost over the first 12 months from initial presentation of a
healed DFU was 2138 ₤, an unhealed DFU 8786 ₤ and an amputated DFU 16941₤ [83].
Presence of infection greatly increased the costs of DFU treatment, ranging from 2604 ₤ for
a non‐infected DFU, up to 12 995 ₤ for an infected DFU.
Research has also been conducted on the cost‐effectiveness of several strategies to prevent
DFU and LEA. One report [84] found that it was more than 90% likely for primary preven-
tion to be cost‐effective if annual prevention costs are inferior to 50 US$ per person and/or
reduces the incidence of DFU by at least 25% in people with diabetes; and in subjects at
moderate or high risk of DFU if costs are inferior to 150 US$ per person and/or the incidence
of DFU decreases at least 10%. Another study from Ireland concluded that the creation of a
dedicated bi‐weekly multi‐disciplinary foot protection clinic was effective in reducing major
LEA and saved 114 063€ per year [85]. In Australia, it was found that at five years, imple-
menting optimal care for patients at high risk of DFU would be cost‐saving and improve
health benefits, measured in quality‐adjusted life years, when compared to usual care [86].
For secondary prevention and including direct and indirect costs in Peru, standard care
(following the International Diabetes Federation guidelines) prevented 791 deaths and was
cost‐saving when compared to sub‐optimal care (consisting in annual medical visit without
appropriate education or footwear provided); and standard care plus temperature monitor-
ing represented an incremental cost ratio (defined as the difference in cost between two
possible interventions, divided by the difference in their effect) of 9405 US$, meaning that
the increase in efficacy represented an extra cost of merely 9405 US$ and prevented 1385
deaths when compared to sub‐optimal care [87]. In Thailand, continuing treatment of indi-
viduals following DFU healing by a multidisciplinary diabetic foot protocol resulted in a
significantly lower average cost and greater QoL as reflected by higher SF‐36 values when
compared to standard care [88]. An intensified (specialized diabetic foot clinic) versus
standard DFU treatment (general practitioners’ clinics) reduced the annual direct costs by
28.9% per patient in grade A DFU and up to 49.7% in grade D by diminishing LEA rates
[81]. In addition, the average life expectancy for patients treated intensively was greater
than with standard treatment, independent of DFU severity. Multidisciplinary DFU treat-
ment has been found in several studies to be cost‐effective [89].

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 17

Cost of Diabetic Foot Disease in England

Marion Kerr
Insight Health Economics, London, UK

2.1 ­Introduction

Diabetic foot disease entails high costs, both human and financial. In this chapter, we will
look at how these costs are estimated, at the level of costs in one health economy, England,
and at how understanding human and financial costs, and the interaction between them,
can be of value to healthcare decision makers.

2.2 ­Human Costs

To estimate the human costs of any healthcare condition, we need to quantify the numbers
of people affected, the duration of the condition, and the impact it has on quality of life and
life expectancy.

2.2.1 Prevalence and Incidence

The most widely known and feared manifestation of diabetic foot disease is, of course,
amputation. People with diabetes in England are around 23 times as likely to have a leg,
foot, or toe amputation as those without diabetes [1]. Approximately 8 out of every 10 000
people with diabetes undergo major lower extremity amputation (above ankle) each year,
and 18 out of 10 000 have minor amputation (below ankle). There were 2515 major ampu-
tations and 6640 minor amputations a year in England between 2015 and 2018 [2]. There
are no national data in England on the number of people living with the consequences of
amputation. Scottish data indicate that, in 2016, 0.7% of people with diabetes had a record
of ever having had a major amputation [3]. If the pattern were the same in England, there
would be around 21 800 people with diabetes who have had a major amputation.
It is estimated that at least 2% of people with diabetes experience at least one new foot
ulcer each year [4]; in 2016–2017 this would amount to around 62 000 people in England,
1.2 million in Europe, and 8.4 million worldwide. The English estimate is based on a

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
18 2 Cost of Diabetic Foot Disease in England

national count of diabetes prevalence, drawn from primary care records and reported each
year by the National Health Service (NHS) [5]. The European and global estimates are
based on World Health Organization diabetes prevalence data [6].
The total number of people experiencing ulceration in a year is likely to be higher still, as
people who already have an ulcer at the start of the year will not be included in these esti-
mates unless they also develop a new ulcer in the course of the year. It is known that ulcers
can be of very long duration, and that some never heal. Scottish data suggest that 2–2.5% of
the diabetes population has a foot ulcer at any given time ([7] and personal communica-
tion, Graham Leese, Ninewells Hospital and Medical School, Dundee).
It is also important to note that there are believed to be many people with undiagnosed
diabetes, and some of these may also experience foot problems. In England, it is thought
that total diabetes prevalence may be around 20% higher than the figure shown on the
national register [8].
To put the burden of foot ulceration in context, it may be helpful to compare the
­estimated 62 000 new cases a year with the numbers of people developing other diseases
and treatment needs. In England in 2016, 46 000 people were diagnosed with breast
cancer, and 40 000 with prostate cancer; these are the two most common cancers [9].
Each year around 7000 people start renal replacement therapy for end‐stage renal dis-
ease [10], there are approximately 84 000 strokes [11],1 and 97 000 people are diagnosed
with chronic obstructive pulmonary disease (COPD) [12]1 (Figure 2.1).
The 9000 annual amputations are not shown in Figure 2.1, as it is not known exactly how
many people had amputations; some people may have had more than one. It is also not
known how many of those who had an amputation are already included in the foot ulcer
incidence numbers.

120000
Estimated annual incidence, England

100000

80000

60000

40000

20000

0
Renal Prostate Breast Diabetic Stroke COPD
replacement cancer cancer foot ulcer
therapy

Figure 2.1 Estimated annual incidence of diabetic foot ulcers, compared with other treatments
and conditions, England.

1 UK figures have been scaled by population numbers to estimate England incidence.

 2.2 ­Human Cost 19

2.2.2 Quality of Life

To gauge the human cost of diabetic foot disease, it is important to examine not just
­incidence and prevalence, but also impacts on quality of life and mortality.
Both amputations and ulceration can lead to long‐term changes in mobility, living
­conditions, and relationships. They can cause pain and depression, and substantially
reduce quality of life.
Health‐related quality of life is often measured using generic metrics that allow com-
parison with other clinical conditions. These are frequently used in combination with
disease‐specific measures, which may provide more detailed information on aspects of
quality of life that are particularly affected by the disease in question. Generic measures
are important, though, as the ability to compare quality of life impacts across conditions
is essential for decision makers who need to set priorities.
In England, the National Institute for Health and Care Excellence (NICE) has specified
that EQ‐5D is the preferred measure for cost‐effectiveness analysis [13]. EQ‐5D scores are
derived from patient questionnaires covering five domains: mobility, pain/discomfort, anx-
iety/depression, ability to care for oneself, and ability to perform usual tasks. Scores are
recorded on a metric in which 0 represents death and 1 represents perfect health [14].
EQ‐5D can be used in conjunction with survival data to estimate quality‐adjusted life
years (QALYs).
Using the EQ‐5D instrument, a Swedish study recorded scores for patients treated by
a multidisciplinary foot service [15]. The scores recorded for current ulcers and for
major amputation are lower than those recorded in other studies for people with diabe-
tes and macrovascular complications [16]. They are also lower than scores for people
with COPD [17], end‐stage renal disease requiring haemodialysis [18], breast cancer,
and prostate cancer [19] (see Figure 2.2).

1
0.9
0.8
0.7
EQ-5D score

0.6
0.5
0.4
0.3
0.2
0.1
0
n

er

PD

**
er

er

si
io

VC
lc

ly
nc

nc
at

O
U

ia
C
t

M
ca

ca
pu

ot

od

ith
Fo
Am

st

m
at

w
ea

ae
ic

t
or

os

s
Br
et

te
aj

Pr
b

be
ia
M

ia
D

Figure 2.2 EQ-5D scores for major amputation, diabetic ulcer and other conditions. *EQ-5D scores
for cancers vary across studies and by treatment stage. We have taken the lowest recorded scores
from a review of multiple studies. **Macrovascular complications.
20 2 Cost of Diabetic Foot Disease in England

2.2.3 Mortality
People with diabetes who have had amputations are at risk of premature death. Research
suggests that only around 50% of patients survive for two years after major amputation in
diabetes [20]. A German study reported 5‐year mortality of 68% for patients with diabetes
undergoing a first major amputation [21]. The same authors conducted a similar study
looking at people with diabetes who experienced a first stroke. Five‐year mortality for the
stroke cohort was 44% [22]. Other studies report five‐year mortality rates after first major
amputation ranging from 61 to 78.7% [23,24]. These rates are comparable with five‐year
mortality for people with diabetes starting renal replacement therapy (68.4%). [10].
Further research is needed on the contribution of major amputation to mortality risk.
Many people undergoing major amputation will be elderly and may have other conditions,
and complications of diabetes, that will reduce life expectancy.
Ulceration is also associated with increased mortality. A recent UK study reported a
­hazard ratio of 2.48 for death after diabetic foot ulcer, even after adjustment for other
known risk factors [25]. A systematic review of international studies found that five‐year
mortality rates were around 40%. The mean age of patients at ulceration across all the
studies was 64 years and 60% were male [26]. Whilst we cannot calculate precisely the
background mortality risk for the cohorts in these studies without access to patient‐level
data, we can say, by way of illustration, that the general population five‐year mortality
rate, calculated from national life tables for England, for a cohort of 64 year olds, of
whom 60% are male, is 5.5%. Net five‐year mortality in people aged 60–69 is 7.6% for
breast cancer and 6.2% for prostate cancer [27]. (Net mortality excludes mortality from
other causes).

2.3 ­Financial Costs

In this section our focus will be on the healthcare costs of diabetic foot disease. It is impor-
tant to remember, however, that these are not the only financial costs that arise. Depending
on the structure of care systems in each country, social care costs may also be incurred, and
there are other financial implications too for patients, their families, and the public sector.
Ulcers and amputations often impede people’s ability to work and to care for themselves,
either temporarily or permanently. In such cases, individuals may lose income, and govern-
ments may lose tax revenue and incur welfare costs.
A number of studies have estimated the healthcare costs of diabetic foot care, at either
individual patient or aggregate level. US studies have reported that the cost of care in the
first year after foot ulcer diagnosis is up to five times as high as for people with diabetes
who do not have an ulcer [28], and have estimated the overall costs of diabetic foot care in
the US at US$9–13 billion a year [29]. The Eurodiale study, which compiled data from 14
European centres, reported that costs increased with ulcer severity; the total cost per
patient was more than four times as high for patients with infection and peripheral arterial
disease at inclusion as for patients who had neither [30]. A 2012 study estimated the cost of
treating two foot ulcers, at opposite ends of the complexity spectrum, in five countries [31].
As this study indicates, costs vary substantially across countries owing to differences in
treatment pathways and unit costs. Extreme caution is needed when comparing costs across
 2.3 ­Financial Cost 21

Post-
amputation care
£21m.

Inpatient care:
Primary, amputation
community and £44m.
outpatient care:
ulceration
£501m – £627m.
Inpatient care:
ulceration
£271m.

Figure 2.3 Estimated cost of diabetic foot care, England, 2014–2015.

health economies [32]; cost effectiveness analyses should always use cost data from the
healthcare economy in which the intervention will be implemented.
We recently estimated the cost of diabetic foot care in England in 2014–2015 at £837–£962
million (€1.1–€1.2 billion and US$1.4–US$1.6 billion, based on the exchange rates on 1st
October 2014), equivalent to almost 1% of the health service budget for England [33]. These
estimates were derived from a combination of national data (for hospital admissions), local
data (for severe ulcers) and study evidence (for less severe ulcers) (see Figure 2.3).
We examined national data for all hospital admissions in England in 2014–2015, and
identified those that included diabetes and foot ulcers or amputations, using diagnosis and
procedure codes on patient records. Costs were estimated using national tariffs for amputa-
tion admissions and admissions that were primarily or exclusively for ulcer care. For other
admissions we estimated the cost of excess bed days relative to people with diabetes who
did not have ulcers.
For care outside hospital there are no comprehensive national datasets. We used local
data from North West London on care received by patients with severe ulcers, and study
data for resource use for less severe ulcers [34]. Staff and medication unit costs were taken
from published sources [35–37].
Notably, more than 90% of the cost we estimated was related to ulcers rather than amputa-
tions. This is in line with another recent UK study, which estimated patient‐level diabetic foot
care costs in 2012–2013 from primary care data, and reported that 87% of these costs were
ulcer‐related [38]. Whilst amputations can have a devastating impact on individual lives, and
unit costs are high, the much higher incidence of ulceration leads to higher aggregate costs.
The distribution of costs by healthcare setting was also noteworthy in our study; two
thirds of costs were in primary, community, or outpatient settings. For much community
care, such as district nursing services, there are no patient‐level datasets in England, and
block contracts are often used for funding. Thus budget holders generally do not know how
resource use in these areas is distributed amongst patient groups. The high costs of diabetic
foot ulcers are largely invisible.
22 2 Cost of Diabetic Foot Disease in England

2.4 ­Why Measure Costs?

Decision‐makers and budget‐holders in healthcare face a huge challenge; they are meant
to ensure that every penny or cent spent on healthcare is spent in the best way possible, to
extract the maximum health gain. (They may also have other priorities such as reducing
inequalities, or promoting research, but maximizing health gain is generally a key aim).
The problem is that allocating resources optimally across the board would require perfect
knowledge about the costs and benefits of every treatment for every condition. Needless to
say, this is impossible. Not only do decision‐makers lack information about the cost and
benefits of many treatments, much of their money is spent in ways they do not fully under-
stand, and patterns of healthcare delivery in many areas are shaped by custom and practice
as much as by evidence.
In the world of imperfect knowledge in which they have to operate, one thing decision‐
makers can do is to identify priority areas for action. In general, priority areas will be ones
where there is the potential to make a substantial improvement to people’s lives in an
affordable way – even better if it is possible to make the improvement and reduce costs at
the same time.
So, in deciding whether a clinical area such as diabetic foot care should be a priority, deci-
sion‐makers are likely to ask some or all of the following questions:
●● How many people are affected?
●● How severe is the impact on their lives?
●● How much does current care cost?
●● What is the potential for changes in care to improve lives?
●● How much will it cost to make these changes (and are there offsetting savings)?
●● How does the balance between costs and benefits compare with those that could be
achieved by adopting a different strategy? Or a different priority altogether?
The areas we have examined so far in this chapter provide answers to the first three of
these questions, in the context of the English health service. Our analysis of quality of life,
mortality and costs has also revealed detail that may be surprising to many decision‐­
makers. National quality indicators and studies of foot care initiatives tend to focus on
amputation rates as the key outcome measure. In part this is because better data are
­available on amputations than on ulcers. Our examination of human and financial costs,
however, suggests that ulcers are associated with substantial quality of life and mortality
impacts, and account for nine tenths of diabetic foot healthcare expenditure.
The scale of the human and financial costs indicates that diabetic foot disease merits the
attention of decision‐makers, and that ulcers are important as well as amputations.

2.5 ­Establishing Healthcare Priorities

In setting healthcare priorities, it is important to examine the quality of existing care, the
scope for improvement, and the clinical and cost effectiveness of alternative approaches.
These are the issues addressed in the last three of the decision‐makers’ questions.
Knowledge of human and financial costs is essential for assessing cost effectiveness.
 2.5 ­Establishing Healthcare Prioritie 23

2.5.1 Care Quality and Scope for Improvement

National guidelines from NICE, in England, stipulate that all areas should have clear path-
ways for diabetic foot care, including a foot protection service and a multidisciplinary foot
service. People with active diabetic foot problems should be referred for expert assessment
within one working day, and triaged within one further working day [39].
There are no comprehensive data on performance against these standards. However, a
recent audit indicates that the basic framework for diabetic foot care, as defined by NICE,
is missing in many places, that (excluding patients who self‐refer) almost 40% of people
with ulcers wait at least two weeks for first expert assessment, and that delays in assess-
ment are associated with increased ulcer severity and longer ulcer duration [40]. The major
amputation rate varies sevenfold across the country, after adjustment for age and ethnicity
[41]. Whilst amputation rates are an imperfect measure of care quality, a variation of this
magnitude, combined with the audit findings on care provision, does suggest that there is
scope for improvement in care quality in many parts of the country.

2.5.2 Clinical Effectiveness

Clinical effectiveness of interventions is covered in detail in other chapters. Most studies
have focused on the structure of care pathways, and speed of access to specialist care. There
is little scientific data from trials on the relative effectiveness of alternative therapies or
products [42]. Observational studies have indicated that it is possible to identify people
with diabetes who are at risk of ulceration [43, 44], that targeted preventive services can
improve outcomes, [45–47] and that early access to multidisciplinary specialist care for
patients with ulcers can reduce ulcer duration, improve healing rates, reduce amputations
and increase survival rates [48–51].

2.5.3 Cost Effectiveness

Where healthcare resource allocation questions are tackled systematically (for example by
NICE, in England) the approach generally relies heavily on cost effectiveness analysis [52].
This involves examining the marginal costs and benefits of an intervention, relative to a
comparator (often usual care). In the case of NICE, benefits are measured in QALYs and
these are derived using EQ‐5D quality of life measures (see Section 2.2.2), combined with
survival impacts. An extra year of life with an EQ‐5D value of 0.25 would yield a QALY gain
of 1 × 0.25 = 0.25.
If an intervention leads to QALY gains and cost reductions, relative to a comparator, it is
clearly cost effective, relative to that comparator. (It is important to remember that cost
effectiveness is always relative to a comparator, and the results may vary substantially
depending on the choice of comparator).
If an intervention leads to QALY gains and cost increases, then assessing cost ­effectiveness
is more complicated. The question that arises is whether the extra money could be better
spent on some other intervention, possibly in another disease area, where cost effectiveness
(QALY gain per pound spent) is higher. Because of the impossibility of assessing the cost
effectiveness of every pound spent for every condition and every treatment, in practice
24 2 Cost of Diabetic Foot Disease in England

decision makers often use a threshold for cost effectiveness; in the case of NICE,
­interventions that yield a cost per QALY of less than £20 000–£30 000 are generally judged
cost ­effective and recommended for adoption.
The evidence set out earlier in this chapter, on EQ‐5D values, mortality and costs of care,
provide many of the building blocks for cost effectiveness analysis of diabetic foot
interventions.

2.5.3.1 Costs and Benefits: An Example

In 2007–2010, amputation rates in the West of England were amongst the highest in the
country. Local clinicians, commissioners and providers conducted a peer‐review of services
in the region and developed 10 criteria for diabetic foot services.
Between 2013 and 2016, major amputation rates fell substantially in the CCGs that
changed their services to meet most or all of the 10 criteria. There was no change in ampu-
tation rates in those that did not increase their score against the 10 criteria [53].
One of the CCGs that improved its foot care service was Somerset. Its major amputation
rate is now below the England average. We worked with Somerset CCG to estimate the cost
and QALY impacts of their service change [54].
We estimate the cost of the changes to the foot care service in Somerset at £157 000 a year
(including set‐up costs which were averaged over three years).
The annual major amputation rate per 1000 adults with diabetes in Somerset fell from
1.61 (95% Confidence Interval (CI) 1.32–1.92) in 2008–2011 to 0.92 (95% CI 0.71–1.12) in
2012–2015. Minor amputations increased non-significantly from 3.18 (95% CI 2.76–3.60)
per 1000 in 2008–2011 to 3.22 (95% CI 2.84–3.60) in 2012–2015. It is estimated that there
were 20 fewer major amputations per year in 2012–2015, and one additional minor ampu-
tation per year, than there would have been if the rates had stayed at the 2008–2011 level.
The number of days in hospital for diabetic foot disease per 1000 adults with diabetes fell
from 248.30 (95% CI 245.09–251.51) to 191.05 (95% CI 188.41–193.69) over the same period.
Cost savings from averted amputations and reduced bed days are estimated at £926 000,
almost six times the cost of the service improvement. The number of lifetime QALYs
gained per averted major amputation is estimated at 3.13 (62.59 for a one-year cohort in
which 20 major amputations are averted).
Our analysis suggests that the service improvement in Somerset was highly cost effective,
with QALY gains and savings that outweigh costs.

2.5.3.2 Limitations
Our Somerset example illustrates two typical features of cost effectiveness analysis as
applied to diabetic foot care. First, it is incomplete. No data were available on ulcer inci-
dence or duration. As we explained earlier, 90% of estimated costs for diabetic foot care are
ulcer‐related. Observational studies and audit data indicate that early access to expert care
is associated with lower ulcer duration. It is likely therefore that improvements in the foot
care pathway should lead to faster healing. If so, there would be additional cost savings and
QALY gains. However, in the case of Somerset, we do not know.
Second, the costs and benefits estimated are specific to Somerset. If another area of the
country were to redesign its pathway to meet the West Country’s 10 criteria, as Somerset
did, the costs and benefits would be different. Why? Because costs and benefits are measured
 2.6 ­Conclusion 25

relative to a starting point, and that will differ from place to place. The cost of change will
depend on what needs to be added to the existing service, and the potential for improved
outcomes will depend on the quality of care at the outset; the poorer the outcomes at the
beginning, the greater the scope for improvement.
This issue arises because, in general, efforts to improve diabetic foot care and outcomes
focus on changing pathways rather than clinical practice. (And it is right that they should do
so; a number of observational studies have shown that pathway change can improve out-
comes, whereas there is a paucity of scientific data on the merits of alternative treatments).
But it is in the nature of pathway reform that the costs and impacts will vary from place to
place, whereas there is likely to be less variability in the costs and impacts of a new therapy.
This variability can be a barrier to improvement. It means that, whilst local areas can
learn the elements of a good care pathway from national guidelines, and can gain practical
advice from each other about how to make change, each area must analyse its own costs,
outcomes, and processes to work out exactly what change is needed, and to estimate the
likely costs and benefits.

2.6 ­Conclusions

The evidence we have presented in this chapter indicates that diabetic foot ulcers and
amputations are very costly, in human and financial terms. Around 2% of people with dia-
betes are thought to develop a new foot ulcer each year. In England, that is around 62 000
people. Some of these ulcers never heal. There are about 2500 major amputations in people
with diabetes in England each year.
Health‐related quality of life for people with diabetic foot ulcers is lower than for other
chronic diseases and the most common cancers. After major amputation, quality of life is
lower still.
Studies indicate that five‐year mortality rates are at least 60% after major amputation,
and around 40% after ulceration.
The financial cost of diabetic foot care in England in 2014–2015 is estimated at £837–£962
million, equivalent to almost 1% of the health service budget. In addition there will be other
costs to individuals, families and the public sector. With increasing prevalence of diabetes
and of risk factors for foot disease, it is likely that these costs will grow in future unless the
quality and outcomes of diabetic foot care are improved.
Around 90% of estimated expenditure is for ulcer‐care. Observational studies have indi-
cated that early access to specialist care can reduce ulcer duration and improve healing rates.
It is likely that measures to reduce ulcer severity and duration will need to play an important
part in any strategy to maximize the benefits of diabetic foot care and control its costs.
In most countries, there is a shortage of routine data on foot ulcer incidence, duration,
and associated resource use. Lack of knowledge in these areas can contribute to a neglect
of ulcer care by decision‐makers.
In England in recent years the National Diabetes Footcare Audit has provided valuable
new information on ulcer care, and on the new elements of care delivery that link most
closely to outcomes; already it indicates that delayed expert assessment is closely related to
worse prognosis.
26 2 Cost of Diabetic Foot Disease in England

The existence of national datasets in the U.K., and of a universal healthcare system,
s­ upports cost analysis of the kind set out in this chapter. Whilst care structures and unit
costs will vary from country to country, the rising human and financial cost of diabetic
foot disease is a global issue. Understanding these costs is an important first step to con-
taining them.

R
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Metabolism Research and Reviews 32 (Suppl 1): 154–168.
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diabetes: a systematic review and meta‐analysis. QJM 100: 65–86.
44 Leese, G.P., Reid, F., Green, V. et al. (2006). Stratification of foot ulcer risk in patients
with diabetes: a population‐based study. International Journal of Clinical Practice 60:
541–545.
45 McCabe, C.J., Stevenson, R.C., and Dolan, A.M. (1998). Evaluation of a diabetic foot
screening and protection programme. Diabetic Medicine 15: 80–84.
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the secondary prevention of foot ulcerations in diabetic subjects. Diabetes Care 26:
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49 Krishnan, S., Nash, F., Baker, N. et al. (2008). Reduction in diabetic amputations over 11
years in a defined U.K. population: benefits of multidisciplinary team work and
continuous prospective audit. Diabetes Care 31: 99–101.
50 Canavan, R.J., Unwin, N.C., Kelly, W.F. et al. (2008). Diabetes‐ and nondiabetes‐related
lower extremity amputation incidence before and after the introduction of better organized
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Care 31: 459–463.
   ­Reference 29

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53 Paisey, R.B., Abbott, A., Levenson, R. et al. (2018). Diabetes‐related major lower limb
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54 Kerr, M. (2017). Diabetic Foot Care in England: An Economic Study. Diabetes UK.
 31

Epidemiology of Amputation and the Influence

of Ethnicity
Caroline A. Abbott
Research Centre for Musculoskeletal Science & Sports Medicine, Department of Life Sciences, Faculty of Science &
Engineering, Manchester Metropolitan University, Manchester, UK

As the global prevalence of diabetes mellitus continues to rise, estimated at 8.4% in 2017
and corresponding to 451 million people [1], there has been a plethora of published
research on the epidemiology of diabetic amputation over the last 10 years [2, 3].
Diabetes increases the risk of lower‐extremity amputation (LEA) by 10–20 times [4] and
is associated with half of all LEAs globally [5, 6]. Despite favourable success rates with
limb salvage methods for diabetic foot patients, long‐term survival following LEA is
poor, with high mortality rates (46%) at five years for first major LEA [7], reduced qual-
ity of life and very high healthcare service costs, due to prolonged inpatient stays and
co‐morbidities [4, 7].

3.1 ­Why Study the Epidemiology of LEA?

Examination of the epidemiology of amputation is valuable for a number of reasons.

Firstly, it enables identification of key risk factors and their relative importance, providing
evidence for the likely benefit of interventions to potentially reduce diabetic LEA risk [4,
6]. Secondly, geographical differences in rates and time trend data demonstrate the impacts
of changes in risk factors and effects of interventions. However, there is increasing concern
that non‐standardized reporting and data capture methods in such studies may contribute
to conflicting published incidence rates [2, 3]; these issues will be discussed further in the
Chapter in relation to geographical variation in LEA incidence. Thirdly, LEA incidence
may also be considered a useful surrogate marker of failure of diabetic foot ulcers to heal,
and therefore may be useful to estimate the size of the global problem in diabetic foot ulcer
management [8].

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
32 3 Epidemiology of Amputation and the Influence of Ethnicity

3.2 ­LEA Incidence Study Design: The Risk of Bias

Study bias can be reduced by considering a number of key elements, recently reviewed by
Narres et al. [3]. Studying large, population‐based cohorts will minimize the effect of selec-
tion bias, yet other sources of bias can impact. Major LEA should be relatively easy to identify
via surgical intervention databases/lists, and, indeed, much of the research on LEA epidemi-
ology is based on examination of such records [9, 10]. However, limiting the search to operat-
ing lists, hospital discharge systems or referrals to limb‐fitting centres results in the likelihood
that a number of major LEA cases will be missed. Therefore, neighbouring‐district hospital
databases should be searched to ensure cross‐boundary capture.
Miscoding of diabetes diagnosis in admission/discharge records is a common problem
and may result in diabetes definition discrepancies and under‐reporting of diabetes inci-
dence, thus diabetic LEA incidence, by up to 15%. Undiagnosed diabetes mis‐classified as
‘non‐diabetic’ is also considered a similar potential problem. Furthermore, a lack of dif-
ferentiation between Type 1 and Type 2 diabetic patients in ‘diabetic populations’ means
that the natural history, incidence, and time trend of LEAs between Type 1 and Type 2
diabetes cannot be explored [3].
The definition for ‘major LEA’ can vary considerably between studies – from ‘any LEA
above the ankle joint’ to ‘through or proximal to the tarso‐metatarsal joint’ [11]; the result-
ing ambiguity in the definition of hindfoot amputations as major or minor LEA would
significantly affect LEA rates between studies, therefore a standardized definition for site
of major and minor LEA is certainly required. As minor amputation is often performed
alongside lower limb revascularisation in attempted limb salvage, whereas major amputa-
tion represents a failure of limb salvage techniques, correct definition is essential.
Estimation of high‐quality age‐ and gender‐specific data on diabetes prevalence in popula-
tion‐based studies is probably the most difficult problem to overcome however. This provides
the denominator for the incidence rate calculation so has the potential to cause large discrep-
ancies in LEA rates. The gold‐standard source would be a high quality population‐based
diabetes register [12]. In reality, however, the estimated prevalence of diabetes is often used,
relying upon source data from prevalence studies, national health surveys or routine census
data, which is less reliable due to the high prevalence of unknown type 2 diabetes.
The above study design elements can, and do, vary from study to study. Indeed, a review
of global reports of LEA incidence highlights the large variations in incidence of LEA that
exist (annual incidence ranging from 4.6–960/10000 people with diabetes) [2]; these varia-
tions can be partly explained by the role of diabetes and its complications, yet rates are also
affected by the non‐standardized aspects of study design.

3.3 ­LEA Risk Assessment Study Design

Studies to assess amputation risk do not necessarily require a comprehensive collection of

all amputation cases, but proper attention to high quality data on risk factors in a sample of
cases for amputation. Many studies have used a case–control approach to identify risk fac-
tors for amputation, whereas a cohort study design, which follows up a very large number of
individuals for a number of years to determine development of amputation with risk factors
 3.4 ­Risk Factors for LE 33

measured to a standardized protocol, is considered best. The FIELD Study, a randomized

controlled trial of fenofibrate on major and minor amputation events, studying 9795 patients
with Type 2 diabetes over five years [13] is an example of such a study: a very large cohort,
of long duration, assessing a very large set of baseline variables. Similarly, the Fremantle
Diabetes Study is an elegant example of a longitudinal assessment, observing 1294 Type 2
diabetic patients over approximately 10 years for LEA predictors [4]. Indeed, risk assessment
studies would ideally assess changes in risk factors over time, such as repeated measures of
glycaemic control and lipid parameters, incidence and progression of neuropathy, foot pres-
sures, foot deformity and more sophisticated measures of peripheral arterial perfusion.

3.4 ­Risk Factors for LEA

The variety of clinical, environmental, demographic and socioeconomic risk factors attrib-
uted to LEA development indicates a complex aetiology. Being male, increasing age, being
African American, having nephropathy, IHD, hypertension or having chronic foot ulcera-
tion each elevates the risk of diabetes‐LEA [14]. The key, independent, clinical risk factors
for LEA in diabetes, consistently, are a combination of peripheral neuropathy and periph-
eral arterial disease (PAD) [4, 6, 15]. The presence of both neuropathy and PAD leads to a
cascade of events, beginning with foot trauma and ulceration due to loss of protective sen-
sation, then subsequent infection, faulty healing due to impaired peripheral circulation,
ultimately leading to amputation [16]. A large prospective study of over ~16 000 patients
with diabetes identified that impaired monofilament sensation and absent foot pulses were
each associated with a ~sixfold increase in LEA, validating these key factors [15].
Poor glycaemic control is also an independent risk factor for LEA with risk of amputa-
tion increasing with increasing levels of HbA1c [4]. A recent meta‐analysis has concluded
that smoking is a clear risk factor for diabetes‐related LEA, with more smokers being prone
to develop severe PAD, although there was no marked distinction for risk of minor or major
amputation in the amputation group [17]. Smoking cessation however may be a good way
to reduce the LEA risk.
In a large multi‐ethnic cohort of diabetic patients, elevated triglyceride levels were asso-
ciated with LEA, independent of other lipid components of dyslipidaemia, identifying TG
as a potential modifiable target [9]. The FIELD study showed a remarkable ~50% reduction
in minor amputations after five years of treatment with Fenofibrate for hyperlipidaemia
[13]. Rather than a lipid‐mediated effect, improvements to peripheral tissue ischaemia via
enhanced endothelial dependent vascular reactivity and improved flow‐mediated dilator
response to hyperaemia were suggested to be the mechanism for the microvascular benefits
of fenofibrate and its impact on LEA rate.
Non‐clinical factors also make a contribution to amputation risk. Good quality ­healthcare
and patient compliance with medical advice can help normalize the clinical risk factors
mentioned above. Increased patient empowerment, with improvements to regular foot
inspections, better foot hygiene and wearing appropriate footwear should reduce progres-
sion of foot problems and highlight the presence of infection or injury at an early stage
when intervention is more likely to be successful such as vascular limb salvage techniques
to save the foot.
34 3 Epidemiology of Amputation and the Influence of Ethnicity

In a recent nationwide study of the Finnish diabetic population, low socioeconomic

s­ tatus showed an increased risk of first major LEA; furthermore, the incidence of first
major LEA decreased significantly with increasing income [18]. Low socio‐economic sta-
tus is known to cause disadvantages for people at all points of the care process, creating
physical barriers to getting to sources of healthcare, especially in countries where higher
quality care depends upon the ability to pay, helping to explain its strong association with
LEA. Furthermore, worse hyperglycaemia and higher smoking rates in the lowest socio-
economic groups will also will partly explain the higher LEA risk.

3.5 ­Incidence Rates of LEA

Global variation in reports of diabetes‐related amputation are high and it is often difficult
to directly compare rates due to the variation in reporting methods used. However, despite
differences in reported diabetes prevalence and fluctuations in international and regional
LEA rates, it is clear and consistent that diabetes mellitus increases incidence and mortality
of LEA [4, 7].

3.6 ­International and Regional Differences

In the UK, approximately one in three amputees has diabetes. The Global Lower Extremity
Amputation Study demonstrated the high levels of association between diabetes and LEA
worldwide, but the wide regional and international variations in incidence that occurred
could not be fully explained by geographical differences in diabetes prevalence [5]. An
international comparison showed a higher incidence of LEA in both diabetic and non‐dia-
betic populations in the USA compared with Europe up until the early 2000s (48.7/105
adults with diabetes in USA vs. 25.1/105 adults with diabetes in Europe [Netherlands])
[10, 19], whereas incidences had converged by 2010 (28.4/105 adults with diabetes in USA)
[10]. Large regional variations in incidence and relative risk of diabetes‐related LEA also
occurred in both of these countries and were considered to be influenced by differences in
distribution of ethnic minority groups, access to healthcare, plus organization and quality
of diabetes care. In the UK, there has been shown to be a 10‐fold variation in the incidence of
major amputation between the Primary Care Trusts, which also points to variations in
organization or delivery of care [20].

3.7 ­Time Trends in LEA Rates

On balance, there is considerable evidence from time trend data that diabetes‐related amputa-
tion rates have declined over the past 20 years [19–22], although some studies do not show this
trend [23]. For example, amputation risk reduced by 40% in the Netherlands between 1995
and 2000, coinciding with an almost doubling in provision of podiatrists and multi‐discipli-
nary foot teams [19]. Explanations for such comprehensive improvements may include the
better provision of multidisciplinary footcare, diabetes care, tighter control of hypertension
 3.9 ­Ethnic Differences in Diabetes-Related LEA Ris 35

and hypercholesterolaemia, improvements to bypass surgery plus new endovascular revascu-

larisation techniques for patients with PAD [3]. As observed by Jeffcoate et al. [8], overall
incidence of major LEA is falling in some countries with nationwide databases [12, 19].
Indeed, UK unadjusted LEA rates have fallen dramatically since mid‐1990s, from 3.0–3.5/1000
adults with diabetes per year to <1.0/1000 per year in both England and Scotland [20, 21].
This improvement has occurred without major change in treatments but following NICE
guidelines on the management of diabetic foot ulcers in 2004, updated in 2010 and 2016.
Furthermore, abrupt and major falls in LEA rates have also occurred in English and German
regional centres, simply by implementing change in the local structure of care and encourag-
ing early referral of all new DFUs [11, 24]; enhanced diabetic foot service provision in SW
England directly improved diabetes‐related major LEA incidence [22].
Examining LEA rates according to diabetes type, however, shows a distinction in time
trends; LEA rates increased in Type 2 diabetes between 2001 and 2008, whereas Type 1
rates decreased, in Spain and Romania [23, 25]. In secondary care in the Netherlands, the
overall diabetes‐related LEA rate has remained constant since 2007 [26]. Examples of study
incidence rates of diabetes‐related LEAs in recent years, illustrating this global variation, is
given in Table 3.1.

3.8 ­Ethnic Differences in Diabetes-Related LEA

3.8.1 Why Study Ethnic Differences in LEA?

The study of ethnic differences in amputation has contributed substantially to our under-
standing of the aetiology of this outcome. There are multiple risk factors for LEA, and teas-
ing out which are causally independent, which are downstream on the causal pathway and
which are simple confounders is the next challenge. Risks and correlates of disease may
differ by ethnicity, breaking the natural confounding between disease and risk factors in
majority populations. For example, people of Indian Asian descent living in the UK have
relatively high risks and levels of cardiovascular disease, compared with equivalent White
European populations, yet, paradoxically, the UK Indian Asian risks of both diabetes‐
related LEA and foot ulcers are substantially lower (four‐ and threefold, respectively) than
that for White Europeans [29, 30], despite vascular abnormalities being independent risk
factors for both CV and LEA. Studies such as these have allowed exploration of potential
confounders to determine which factors may account for ethnic differences in LEA and its
precursor, foot ulceration.

3.9 ­Ethnic Differences in Diabetes-Related LEA Risk

3.9.1 Native Americans

Native Americans have one of the highest rates of diabetes‐related amputation in the world
[31]. Risks of amputation are eightfold higher in type 1 diabetes and threefold higher in
type 2 diabetes, compared with European populations, yet risk factors were similar within
both ethnic groups [31]. In type 2 diabetes these were disease duration, glucose, male
Table 3.1 Global variation of incidence of diabetes-related lower extremity amputations (LEAs)
in recent years.

Incidence
Author (per 10 000 Year of Level of
[Reference] persons) study amputation Population Region

Leggetter [27] 14.7 1992– All LEA Black‐African with London, UK

1997 diabetes
21.9 White European with
diabetes
Gregg [10] 28.4 2010 All LEA Total diabetic USA
population
40.0 Black with diabetes
20.4 White with diabetes
Canavan [11] 17.6 2000 All LEA Total diabetes North‐East
England,
UK
Ikonen [12] 4.8 2007 Major LEA Total diabetes Finland
(1st)
Van Houtum 36.3 2000 All LEA Total diabetes Netherlands
[19]
Holman [20] 25.1 2007– All LEA Total diabetes England
2010
15.7 Minor LEA
9.9 Major LEA
Kennon [21] 11.1 2008 Major LEA Total diabetes Scotland
21.3 All LEA
Lopez‐de‐ 0.75 2008 Major LEA Total Type 2 diabetes Spain
Andres [23] (excl trauma)
1.1 Minor LEA
(excl trauma)
Veresiu [25] 2.6 2010 All LEA General population Romania

77.9 Total diabetic

population
Nijenhuis‐ 45.9 2011 All LEA Total diabetes The
Rosien [26] (excl trauma) Netherlands

14.2 Major LEA

36.2 Minor LEA

Suckow [28] 17.8 2002– Major LEA Black‐African descent
2012 (1st) Medicare diabetic
population > 65 years

11.5 Hispanic Medicare

diabetic
population > 65 years

5.6 White Medicare

population with
diabetes >65 years
 3.9 ­Ethnic Differences in Diabetes-Related LEA Ris 37

g­ ender, presence of other microvascular complications, i.e. retinopathy and nephropathy

and raised triglycerides. None of these factors, however, singly or in combination could
account for differences between Native Americans and Europeans; it was suggested that
differences in access to healthcare could explain the LEA relative risks observed.

3.9.2 Hispanic Americans

Studies of Hispanic American LEA risk has been variously reported to be higher, equiva-
lent to, or lower than that of non‐Hispanic White populations in USA. This disparity may
be due to variable differences between Hispanic and non‐Hispanic populations in self‐care
and access to high‐quality medical care, rather than neuropathy and PAD which did not
differ between the ethnic groups. Mexican Americans, however, were less likely to undergo
lower extremity bypass surgery, more likely to be categorized as unsuitable for bypass, and
more likely to have a failed bypass [32]. Therefore, although differential access to high‐
quality healthcare and poor self‐footcare in Mexican Americans is clearly a problem, the
authors hypothesize that higher amputation rates in Mexican Americans reflected a greater
prevalence of non‐re‐constructible distal vessels [32]. Since then, between 2002 and 2012,
the average major LEA rate (1.15 per 1000 per year) in Hispanic diabetic Medicare patients
has steadily declined, with a 61% reduction in amputation rate over the 10‐year study
period, concurrent with similar reductions across other racial groups [28].

3.9.3 Populations of Black African Descent

The inter‐relationships between diabetes‐related risk factors, cardiovascular risk fac-
tors, and the importance of healthcare access and socioeconomic status have been
revealed by worldwide studies of people of Black African descent. Early reports showed
that the diabetes‐related amputation risk for US African Americans was two‐ to three-
fold higher than that for US Whites. Risk factors such as smoking, low socioeconomic
status and, crucially, poor access to healthcare, appear to account for much of this
increased LEA risk [2]. African American ethnicity per se appears to be an independent
risk factor for LEA, but only in the USA, and likely because people of Black African
descent have poorer access to good quality health insurance and are less likely to
undergo lower extremity revascularisation [3]. In contrast, a different epidemiological
story emerges in the UK. The United Kingdom is a setting where access to healthcare
should be equitable, being free at the point of delivery. Indeed, incidence rates for LEA
are substantially lower in Black African descent populations compared with White
Europeans in England (147 per 105 vs. 219 per 105) [27], or rates are comparable, at least
[20]. The reason for these contrasting findings are likely to be due to the organizational
differences of private healthcare in the US and public healthcare in the UK, with additional
effects from lower PAD levels in UK Black Africans.
Amputation rates are very high in the Caribbean, with around 950 per 100 000 ­population
[33], equivalent to those found in the US, but at least threefold higher compared to UK
rates [27]. Risk factor analyses revealed that clinical predictors included glycated haemo-
globin, PAD and neuropathy, yet the most important factor was use of ill‐fitting footwear,
plus inadequate foot self‐inspection. This illustrates the benefit of interventions which
38 3 Epidemiology of Amputation and the Influence of Ethnicity

target not only the healthcare professional but the patient, to reduce exposure to minor
trauma and infection. In summary all these studies illustrate the complex confounding
effects of ethnicity on LEA.

3.10 ­Indian Asians

Studies of the UK South Asian population provide a very different contrast to UK African
Caribbeans. South Asian people worldwide share an elevated risk of stroke, diabetes and
insulin resistance [29, 30] and so resemble the disease profile of African Caribbeans. In
contrast to African Caribbeans, South Asians have much higher risks of IHD compared
with White Europeans, yet paradoxically show a markedly lower risk (one‐quarter) of dia-
betes‐related LEA [29, 30, 34]. Key risk factors that account for this ethnic difference are
the lower rates of PAD, peripheral neuropathy, and smoking in South Asians, attenuating
the risk ratio from 0.26 in favour of South Asians to just 0.84 [30]. This finding is supported
elsewhere by reports of low rates neuropathy and PAD in Asians in UK [29, 35, 36] and
from India [37]. Furthermore, diabetic foot ulcer risk is substantially lower in South Asians
in the UK (one‐third of the risk of equivalent White Europeans), with lower levels of PAD,
neuropathy, and foot deformities accounting for half of this reduced ulcer risk [29]. When
explanations for lower rates of diabetic neuropathy in South Asians were sought, less
smoking and more favourable microcirculation, rather than conventional risk factors such
as glycaemic control and hyperlipidaemia, accounted for their preserved peripheral nerve
function [35, 36]. Comparison of these two ethnic groups for risk factors for LEA, there-
fore, shows the relative importance of physiological differences between South Asians and
White Europeans, in particular, the better preserved vascular responses of the South
Asians. These may well contribute to the more favourable LEA rates in South Asian popu-
lations in the UK compared with White Europeans, rather than the impact of improved
socioeconomic status or better access to healthcare services as for other ethnic minority
comparisons. In New Zealand (NZ), the very low rate of South Asian diabetes‐related LEA
has been suggested to also represent a ‘healthy migrant effect’, as over half of the Asian
people in NZ are recent immigrants (within last 10 years) with markedly lower mortality of
immigrants than those born in NZ [34]. Although a potential explanation in NZ, this would
not account for the low LEA rate for the established UK South Asian population.
To summarize, ethnic variations in the incidence of LEA undoubtedly exist and differ con-
siderably between countries and regions. In addition to the identification of physiological
risk factors which account for some of these ethnic differences, these studies also highlight
the scope that healthcare interventions may have to reduce risk of LEA, including targeting
clinical risk factors, early referrals for DFUs and access to vascular limb salvage techniques.

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26 Nijenhuis‐Rosien, L., Hendriks, S.H., Kleefstra, N. et al. (2017). Nationwide diabetes‐
related lower extremity amputation rates in secondary care treated patients with diabetes
in the Netherlands (DUDE‐7). Journal of Diabetes and its Complications 31: 675–678.
27 Leggetter, S., Chaturvedi, N., Fuller, J.H., and Edmonds, M.E. (2002). Ethnicity and risk of
diabetes‐related lower extremity amputation: a population‐based, case‐control study of
African Caribbeans and Europeans in the United Kingdom. Archives of Internal Medicine
162: 73–78.
28 Suckow, B.D., Newhall, K.A., Bekelis, K. et al. (2016). Hemoglobin A1c testing and
amputation rates in black, Hispanic, and white Medicare patients. Annals of Vascular
Surgery 36: 208–217.
29 Abbott, C.A., Garrow, A.P., Carrington, A.L. et al. (2005). Foot ulcer risk is lower in
South‐Asian and African‐Caribbean compared with European diabetic patients in the
U.K.: the North‐West diabetes foot care study. Diabetes Care 28: 1869–1875.
30 Chaturvedi, N., Abbott, C.A., Whalley, A. et al. (2002). Risk of diabetes‐related amputation
in South Asians vs. Europeans in the UK. Diabetic Medicine 19: 99–104.
31 Chaturvedi, N., Stevens, L., Fuller, J. et al. (2001). Risk factors, ethnic differences and
mortality associated with lower‐extremity gangrene and amputation in diabetes. The WHO
multinational study of vascular disease in diabetes. Diabetologia 44 (Suppl 2): S65–S71.
32 Lavery, L., Armstrong, D., Wunderlich, R. et al. (2003). Diabetic foot syndrome: evaluating
the prevalence and incidence of foot pathology in Mexican Americans and non‐Hispanic
whites from a diabetes disease management cohort. Diabetes Care 26: 1435–1438.
33 Hennis, A.J., Fraser, H.S., Jonnalagadda, R. et al. (2004). Explanations for the high risk of
diabetes‐related amputation in a Caribbean population of black African descent and
potential for prevention. Diabetes Care 27: 2636–2641.
  ­Reference 41

34 Robinson, T.E., Kenealy, T., Garrett, M. et al. (2016). Ethnicity and risk of lower limb
amputation in people with type 2 diabetes: a prospective cohort study. Diabetic Medicine
33: 55–61.
35 Abbott, C.A., Chaturvedi, N., Malik, R.A. et al. (2010). Explanations for the lower rates of
diabetic neuropathy in Indian Asians versus Europeans. Diabetes Care 33: 1325–1330.
36 Fadavi, H., Tavakoli, M., Foden, P. et al. (2018). Explanations for less small fibre
neuropathy in South Asian versus European people with type 2 diabetes mellitus in the
UK. Diabetes Metab Res Rev 34: e3044.
37 Premalatha, G., Shanthirani, S., Deepa, R. et al. (2000). Prevalence and risk factors of
peripheral vascular disease in a selected South Indian population: the Chennai urban
population study. Diabetes Care 23: 1295–1300.
 43

4a

The Diabetic Foot Worldwide: India

M. Viswanathan
WHO Collaborating Centre for Research, Education and Training in Diabetes, Diabetes Research Centre and M.V. Hospital for
Diabetes, Royapuram, Chennai, Tamilnadu, India

4a.1 ­Introduction

Worldwide diabetes and its complications pose a major threat to public health resources.
In developing countries such as India, diabetic foot amputation is a frequent and trouble-
some diabetic complication.

4a.2 ­Epidemiology of Diabetes in India

The developing world is facing a double burden today from diabetes and communicable
diseases like tuberculosis. Recent studies from India show an increasing prevalence of dia-
betes in both urban and rural areas of the country [1]. People with undiagnosed diabetes
in the community have the risk of being diagnosed with advanced diabetic micro vascular
complications. An important point is the higher prevalence of diabetes amongst the people
from the lower socioeconomic status (SES) in the urban areas of the country [1].

4a.3 ­Socio Economic Burden Due to Diabetes

Diabetes causes a serious socioeconomic burden in India and most of the cost is due to
diabetic foot complication [2]. Of all the complications, diabetic foot infection (DFI) is the
most expensive in India, with the cost being four times higher (US$ 409) for patients with
an infected foot ulcer than in those without foot infection (US$ 97) [3]. The high cost for
diabetes care in India is mainly due to the direct and indirect costs involved.

4a.4 ­Common Risk Factors for Amputation in India

Most of the amputations in India occur due to the insensate feet. A multi‐centre study in
India which looked at 1295 amputations in different parts of the country, found that the

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
44 4a The Diabetic Foot Worldwide: India

major cause was infection in the foot which followed loss of sensation in the feet in 82%
of the patients. Peripheral arterial disease was diagnosed in 32% of the patients [4]. Socio
cultural practices such as bare foot walking, use of improper footwear and lack of knowl-
edge about foot care contribute to foot injury and infection. Infection in the insensate
feet is often neglected which then leads to a limb threatening infection [5].

4a.5 ­Diagnosing High Risk Feet in Developing Countries

A simple graduated Rydel Seiffer tuning fork and Tip therm, an inexpensive bedside
method, which detects loss of sensation in the feet helps to identify high risk feet amongst
patients with diabetes in the developing countries and these devices have a high specificity
and good sensitivity compared to the Biothesiometer [6, 7]. The graduated tuning fork is
considered to be a good alternative to the expensive biothesiometer for estimating the
vibration perception threshold.

4a.6 ­Comparison in Risk Factors between India

and the Western World

A multi‐national study from Tanzania, Germany and India was conducted amongst 613
type 2 diabetic patients, to determine the differences in underlying risk factors and clinical
representation of foot problems [8]. It was found that PVD was frequent in Germany, whilst
in Tanzania and India it was far less common. The lower prevalence in India was probably
due to younger age of the patients, shorter diabetes duration, lower proportion of smokers
and ethnicity–related factors. A lesser prevalence of PVD but a higher prevalence of ampu-
tation was noted amongst Indians when compared with those in Western countries, which
was related to progressive infection.

4a.7 ­DFI as a Cause for Declining Kidney Function

An important observation is the fact that repeated DFI leads to worsening kidney function. In
a prospective study of 412 patients with and without CKD, it was observed that there was a
significant reduction in eGFR amongst those who had DFI with pre‐existing CKD and even
amongst those with normal kidney function [9]. This observation has important public health
implications in the developing world since Diabetic Nephropathy is a leading cause of End
Stage Renal Disease (ESRD) and such patients are unable to afford renal replacement therapy.

4a.8 ­Helping People with Amputation Cope Up with the Disability

Amputation is a cause for emotional distress [10]. Post amputation, patients tend to develop
depression, anxiety and disturbed body image [11]. In a prospective study 62 consecutive
patients with Type 2 DM who underwent an amputation, were randomized to an intensive
counselling group and a routine counselling group. In the Intensive counselling, patients
  ­Reference 45

were given every day till they were discharged from the hospital. The patients who were
given intensive counselling were found to have a better quality of life than those who were
given a routine counselling. Therefore, there seems to be need for intensive psychological
counselling for people who undergo an amputation [12].

­References

1 Anjana, R.M., Deepa, M., Pradeepa, R. et al. (2017). Prevalence of diabetes and prediabetes
in 15 states of India: results from the ICMR–INDIAB population‐based cross‐sectional
study. The Lancet Diabetes & Endocrinology 5 (8): 585–596.
2 Tharkar, S., Devarajan, A., Kumpatla, S., and Viswanathan, V. (2010). The socioeconomics
of diabetes from a developing country: a population based cost of illness study. Diabetes
Research and Clinical Practice 89 (3): 334–340.
3 Kumpatla, S., Kothandan, H., Tharkar, S., and Viswanathan, V. (2013). The costs of treating
long‐term diabetic complications in a developing country: a study from India. The Journal
of the Association of Physicians of India 61 (2): 102–109.
4 Viswanathan, V. and Kumpatla, S. (2011). Pattern and causes of amputation in diabetic
patients – a multicentric study from India. The Journal of the Association of Physicians of
India 59 (3): 148–151.
5 Vijay, V., Snehalatha, C., and Ramachandran, A. (1997). Socio cultural practices that may
affect the development of the diabetic foot. IDF Bulletin: 10–12.
6 Vijay, V., Snehalatha, C., Seena, R., and Ramachandran, A. (2001). The Rydel Seiffer tuning
fork: an inexpensive device for screening diabetic patients with high‐risk foot. Practical
Diabetes International 18 (5): 155–156.
7 Viswanathan, V., Snehalatha, C., Seena, R., and Ramachandran, A. (2002). Early
recognition of diabetic neuropathy: evaluation of a simple outpatient procedure using
thermal perception. Postgraduate Medical Journal 78: 541–542.
8 Morbach, S., Lutale, J.K., Viswanathan, V. et al. (2004). Regional differences in risk factors
and clinical presentation of diabetic foot lesions. Diabetic Medicine 21 (1): 91–95.
9 Anitha Rani, A. and Viswanathan, V. (2017). Diabetic foot infection and worsening kidney
function: implication for health care in the developing world. International Journal of
Diabetology & Vascular Disease Research 5 (5): 208–213.
10 Vileikyte, L. (2001). Diabetic foot ulcers: a quality of life issue. Diabetes/Metabolism
Research and Reviews 17 (4): 246–249.
11 Rybarczyk, B.D., Nyenhuis, D.L., Nicholas, J.J. et al. (1992). Social discomfort and
depression in a sample of adults with leg amputations. Archives of Physical Medicine and
Rehabilitation 73 (12): 1169–1173.
12 Amalraj, M.J., Anitha, R.A., and Viswanathan, V. (2017). A study on positive impact of
intensive psychological counseling on psychological well‐being of type 2 diabetic patients
undergoing amputation. International Journal of Psychology and Counselling 9 (2): 10–16.
 47

4b

The Diabetic Foot Worldwide: Pakistan

Abdul Basit
Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan

4b.1 ­Introduction

4b.1.1 Burden of Diabetes and Diabetic Foot

According to International Diabetes Federation (IDF) atlas, 19.4 million people have
­diabetes in Pakistan [1]. Second National Diabetes Survey of Pakistan (NDSP 2016–2017)
has estimated the prevalence of diabetes to be 26.3% [2]. Studies suggest 4–10% of people
with diabetes (PWD) develop foot ulcers [3]. The lower extremity amputation (LEA) rate
following foot ulceration has been reported to be 8–21% [4, 5].

4b.2 ­Concept of Multidisciplinary Diabetic Foot

Care Team (MDFCT)
To the best of our knowledge, the first diabetic foot care clinic in Pakistan was established
in 1996 at Baqai Institute of Diabetology and Endocrinology (BIDE), Karachi, which had a
MDFCT. It included diabetologist, surgeon (with special interest in diabetic foot) and dia-
betic foot care assistant (DFCA). For the training of DFCAs, a structured six weeks course
was initiated. The main objective was to provide low cost diabetic foot care under medical
supervision. Physicians were trained in diabetic foot surgery. Other cost‐effective strategies
included manufacturing and distribution of low‐cost offloading devices developed with
locally available material [6]. Domiciliary foot care service and stationed 24‐hour phone
helpline service was established to improve compliance. All these measures resulted in
reduction of amputation rate from baseline as high as 27.5% (1997–2003) [7] to 3.92% in
(2014–2016) [8] (Figure 4b.1).
The prevalence of peripheral arterial disease (PAD) in PWD was estimated to be 5.5% to
31.6 in 2004 and 2011 respectively [9, 10]. There is an increase in PAD in PWD in Pakistan,
partially explained by better survival rate in PWD. The PAD group has been established

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
48 4b The Diabetic Foot Worldwide: Pakistan

Amputation rate
30.0% 27.5%

25.0%

20.0% 17.3%

15.0%
10.4%
10.2% 8.3%
10.0% 7.8%
7.3% 6.9%
5.0% 6.7% 3.9%
3.1% 2.5%
1.4% 1.1%
0.0% 1.4%
1997–2003 2004–2006 2007–2010 2011–2013 2014–2016
Minor Major Overall

Figure 4b.1 Trends of lower extremity amputation (LEA) rate at a representative tertiary care unit
of Karachi, Pakistan.

which also includes interventional radiologists and cardiologists from various institutions
and with their input healing rate is expected to improve further.

4b.3 ­Nationwide Diabetic Foot Programme

(Step by Step-[SbS])

Pakistan Working Group on the Diabetic Foot (PWGDF) was established in 2006 under
the guidance of Prof. Andrew Boulton and Dr Karel Bakker. Nationwide diabetic foot
care programme was launched in 2007, based on the concept of SbS programme, initially
funded by World Diabetes Foundation (WDF). Under the auspices of this programme,
178 diabetic foot care teams were trained and 115 diabetic foot clinics were established.
The amputation rate at these clinics decreased from 11.5 to 6.6% during the period from
2008 to 2010 [3].
Pakistan is a country with an area of 796 095 km2 and a population of 207.77 million. It
needs around 3000 diabetic foot clinics [11, 12]. Efforts are being undertaken to achieve
this target. Basic courses for foot care teams are being continued and to date, 600 teams
have been trained and further 600 will be trained each year.

4b.4 ­Footwear for Every Diabetic (FED)

‘Feet at Risk’ assessment clinics are established and risk category for each patient is
­identified. Footcare advise is provided and a concept of FED as a project, funded initially
by the WDF has been developed. Training of footwear technicians are conducted under the
supervision of international experts. The trained technicians will subsequently conduct a
train‐the‐trainer programme and the establishment of units for the manufacture of low‐
cost customized footwear is being undertaken.
   ­Reference 49

4b.5 ­Further Steps Ahead of SbS

Advisory Board for the Care of Diabetes has been developed consisting of diabetes units of
10 major teaching institutions in the country. This board develops consensus guidelines,
collaborative researches and concerted management strategies for PWD. Under this board,
virtual weekly foot meetings are held and the cases of diabetic foot across the country are
discussed and MDFCT expertise is shared. More and more diabetes clinics and centres are
able to utilize this network through digital technology which is getting widely available in
the country. Such steps are going to facilitate development of comprehensive diabetic foot
registry under the umbrella of Diabetes Registry of Pakistan. Multiple stakeholders includ-
ing policy makers, media and NGOs are getting more and more involved and all these
measures are expected to reduce the amputation rate further, making it comparable with
the developed centres worldwide.

­References

1 IDF Diabetes Atlas 9th Edition ‐ International Diabetes Federation. https://www.

diabetesatlas.org/en/resources/ [Last reviewed on November 19, 2019].
2 Basit, A., Fawwad, A., Qureshi, H. et al. (2018). Prevalence of diabetes, pre‐diabetes and
associated risk factors: second National Diabetes Survey of Pakistan (NDSP), 2016–2017.
BMJ Open 8: e020961.
3 Basit, A. and Nawaz, A. (2013). Preventing diabetes‐related amputations in a developing
country–steps in the right direction. Diabetes Voice 58 (1): 36–39.
4 Ali, S.M., Basit, A., Sheikh, T. et al. (2001). Diabetic foot ulcer – a prospective study. The
Journal of the Pakistan Medical Association 51 (2): 78–81.
5 Ince, P., Abbas, Z.G., Lutale, J.K. et al. (2008). Use of the SINBAD classification system and
score in comparing outcome of foot ulcer management on three continents. Diabetes Care
31 (5): 964–967.
6 Miyan, Z., Ahmed, J., Zaidi, S.I. et al. (2014). Use of locally made off‐loading techniques for
diabetic plantar foot ulcer in Karachi, Pakistan. International Wound Journal 11 (6):
691–695.
7 Ali, S.M., Basit, A., Fawwad, A. et al. (2008). Presentation and outcome of diabetic foot at a
tertiary care unit. Pakistan Journal of Medical Sciences 24 (5): 651.
8 Riaz, M., Miyan, Z., Waris, N. et al. (2019). Impact of multidisciplinary foot care team on
outcome of diabetic foot ulcer in term of lower extremity amputation at a tertiary care unit
in Karachi, Pakistan. Int Wound J 16 (3): 768–772.
9 Basit, A., Hydrie, M.Z., Hakeem, R. et al. (2004). Frequency of chronic complications of
type 2 diabetes. Journal of the College of Physicians and Surgeons Pakistan 14 (2): 79–83.
10 Akram, J., Aamir, A.U., Basit, A. et al. (2011). Prevalence of peripheral arterial disease in Type‐2
diabetics in Pakistan. The Journal of the Pakistan Medical Association 61 (7): 644–648.
11 Basit, A., Fawwad, A., Siddiqui, S.A. et al. (2019). Current management strategies to target
the increasing incidence of diabetes within Pakistan. Diabetes Metab Syndr Obes. 12: 85–96.
12 Basit, A., Fawwad, A., and Baqa, K. (2019). Pakistan and diabetes‐A country on the edge.
Diabetes Research and Clinical Practice 147: 166–168.
 51

4c

The Diabetic Foot Worldwide: Sub-Saharan Africa

Zulfiqarali G. Abbas
Internal Medicine, Abbas Medical Centre, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

The incidence of diabetes mellitus is increasing across Sub‐Saharan Africa (SSA); a parallel
increase in the number of foot ulcers in these populations has been documented. Data from
SSA suggest that these increases might partly be associated with urbanization. Although
most published reports from SSA suggest that foot ulcers generally are associated with
underlying peripheral neuropathy (PN), recent data establish that peripheral arterial dis-
eases (PAD) is playing a more substantial role in ulcer causation than was previously
thought. Other data from Tanzania indicate that ulcers due to both neuropathy and arterial
disease (i.e. neuroischaemia) are increasingly being seen. Factors associated with poor out-
comes include delays in seeking medical attention, neuroischaemia or ulcers that have
progressed to gangrene at presentation. Key preventive measures include regular inspec-
tion of feet and footwear, education of high‐risk patients, proper foot wear and action of
even minor foot lesions.

4c.1 ­Introduction

Africa, the second largest continent in the World, is three times the size of Europe and is
home to some 1000 ethnic groups living in 55 nations, speaking more than 1000 languages.
Currently with 1.1 billion population, Africa is predicted to increase and reach to 2.4 billion
in 2050. Much of the increase will happen in SSA, which includes 46 countries many of the
world’s poorest countries [1].
The incidence of diabetes mellitus is increasing in the population across the world. SSA
is experiencing a rapid increase in the prevalence of diabetes. In 2019, it was estimated that
there were 19 million persons with diabetes in SSA and should the current trends continue
the overall prevalence is projected to be 47 million by 2045, which is increase of 143% [2].
Diabetes remains a leading cause of morbidity and mortality in both the developed and
developing world and impose a heavy burden on their health services [3, 4]. Amongst all
the various complications, serious complications related to diabetes foot diseases are asso-
ciated with the highest morbidity and mortality [3, 4]. Across the world, data suggest that

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
52 4c The Diabetic Foot Worldwide: Sub-Saharan Africa

40–60% of all lower limb non‐traumatic amputation are related to diabetes [3, 4]. Most
published reports confirm that foot lesions in SSA diabetic patients are associated with PN,
commonly have an infectious aetiology and can be critical and costly [3–7].
Time is tissue, which means that medical assistance should be sought as quickly as
possible. It is not widely known that in a patient with a diabetic foot ulcer, days, weeks
or months, may mean the difference in saving a toe, foot, leg, or even death [4]. These
patients cannot afford to present late to a health centre. Reasons for delayed presenta-
tions in SSA were reported by Abbas et al., and are associated with cultural, traditional,
and customary behaviours [3–6, 8]. Patients in SSA have a tendency to go through sev-
eral stages before reporting to the health centre. They will first try to attempt to treat
small lesions like a callus or a boil at home using a razor blade or herbal solution. These
procedures are carried out by the patients themselves or relatives. If home treatment
fails, the patient’s next move would be to see a faith healer or herbal doctor. When herbal
medications fail, the patient may decide to visit a primary health centre or district or
regional hospitals where no diabetic foot specialist are found. These delays can mean
that the condition of the foot deteriorates, and so by the time they present to a specialist
services, it may be too late to save the foot and sometimes even to prevent death of the
patient [3–6, 8]. Some patients delay getting an expert opinion because of fear losing a
limb, as in SSA, loss of limb is considered a worse outcome than having disease. Lack of
knowledge amongst health care workers at grass root level can also lead to poor outcome
[3–6, 8].

4c.2 ­Pathophysiology of Foot Ulcers

The pathophysiology of diabetic foot lesions is complex and multi‐factorial. Contributory

factors include PN, PAD, infection, biomechanics, social‐economic factors, non‐ulcerative
lesions of ulcers, and local trauma. The pattern of foot ulcer occurrence depends on the
varying degree of contribution of each of these factors. For example, an ulcer may be sec-
ondary to both ischemia and neuropathy – so called neuroischaemic ulcer.

4c.3 ­Peripheral Neuropathy (PN)

Peripheral neuropathy is one of the most common complications affecting patients with
diabetes in both the developed and less developed world [1, 3–6, 8–10]. The resulting loss
of sensation in the feet invariably lead to sequelae that include callosities, cracked soles,
breakdown of skin, or non‐discernable injuries, such as burn or rat bite. These complica-
tions can result in foot ulcers, which can progress to infection, necrosis, gangrene, loss of
limb, or death [1, 3–6, 8–10].
The prevalence of PN rates across the SSA in last two decades has been documented in
several studies and ranges from 25 to 82% [3–6, 8–18], (Table 4c.1). In a major study per-
formed in Tanzania, Abbas et al. found no differences in the rates of PN amongst African
and Asians diabetic patients with ulcers [9, 13]. In another comparative study, Abbas and
 4c.4 ­Peripheral Arterial Diseases (PAD 53

Table 4c.1 Literature review of peripheral neuropathy (PN) rates across the sub-Saharan Africa
in last two decades.

Publication No. of Prevalence of Peripheral

year Author Country Patients Neuropathy (%)

2017 Awadalla H et al. Sudan 424 68.2

2015 Ogbera AO et al. Nigeria 225 37
2015 Kuate‐Tegueu C et al. Cameroon 306 77.4
2012 Owolabi MO et al. Nigeria 277 71
2011 Jarso G et al. Ethiopia 384 48.2
2009 Abbas ZG et al. Tanzania 708 81
2009 Mugambi N et al. Kenya 218 42
2006 Ndip EA et al. Cameroon 300 27.3
2004 Morbach S et al. Tanzania 123 82
2003 Moulik PK et al.a Zambia 185 61
2000 Abbas ZG et al.a Tanzania 200 25.5
a
1997 Wikbald K et al. Tanzania 153 28.1
1997 Levitt NS et al.a South 300 27.6
Africa
a
References marked with an asteriskcan be found in Ref. [5].

colleagues found no significant differences in the prevalence of neuropathy in patients

with foot ulcers from Tanzania, Germany, and India [9]. There is no difference across the
world in the rates of PN [9].

4c.4 ­Peripheral Arterial Diseases (PAD)

PAD is very common in the industrialized world, but was not that common in Africa and
Asia [9]. Time has changed the situation across Africa and Asia, and now the rates of PAD
are increasing [13]. The reasons for this increase are the communities in SSA becoming
more urbanized, following a sedentary lifestyle, lack of exercise, changing diet, etc. As a
consequence, PAD is increasing in people with diabetes in SSA. Prevalence rates of PAD
are increasing from single digit of 3.4% in 1991 to double digit of 42% in 2016 across SSA [5,
9, 11, 13, 17, 19–23], (Table 4c.2). Abbas et al. established that rates of PAD in Tanzania are
not different by ethnicity as it was in the past [13]. PAD is now playing a more substantial
role in the causation of foot ulcer in SSA than was previously thought [13]. Likely, reasons
for this include increased urbanization and adoption of behaviours and diet from the west
[5, 13].
Neuroischaemic lesions are also seen in SSA patients with diabetic foot ulcers and amputa-
tion is the usual outcome. Abbas et al. have documented 17.5% prevalence of neuroischaemic
lesions amongst diabetic patients in Tanzania [5, 13].
54 4c The Diabetic Foot Worldwide: Sub-Saharan Africa

Table 4c.2 Literature review of peripheral arterial diseases (PAD) rates across the sub-Saharan
Africa in last two decades.

Publication Prevalence ofPeripheral

year Author Country No. of patients Arterial Disease (%)

2016 Codjo HL Benin 401 41.9

2015 Ogbera AO Nigeria 225 40
2014 Konin C Ivory Coast 308 22
2014 Mwebaze RM Uganda 146 39
2013 Umuerri EM Nigeria 388 35.6
2009 Abbas ZG Tanzania 708 26
2009 Mugambi NE Kenya 218 12
2007 Kumar A South Africa 542 29.3
2006 Ndip EA Cameroon 300 21.3
2004 Morbach S Tanzania 123 12
2003 MoulikPKa Zambia 185 41
a
2002 Abbas ZG Tanzania 92 21
2000 Abbas ZGa Tanzania 200 12.5
a
1997 Levitt NS et al. South Africa 300 8.2
1995 Lester FTa Ethiopia 43 11.6
1991 ElmahdiEMa Sudan 413 3.4
a
References marked with an asteriskcan be found in Ref. [5].

4c.5 ­Foot Ulceration in SSA

Studies across SSA shows patients with diabetic foot admitted to the inpatient medical ­services
ranging from 12 to 31% [5, 11, 18, 24–29], (Table 4c.3). A study in Tanzania showed that 15%
of patients with diabetes admitted to the inpatient medical services of the largest hospital in
the country have foot ulcers – 80% of these first‐time occurrence [5]. Specific factors contribut-
ing to development of diabetic foot ulcers include bare foot walking (common practice in rural
communities in SSA due to low income or culture), inappropriate foot wear, living at or below
poverty level meaning that the purchase of appropriate footwear might not be feasible or of
high priority, easily sustained trauma due to PN, and delays in seeking medical attention for
seemingly innocuous foot lesions [5]. Abbas et al. have recorded some unusual examples of
foot ulcerations amongst attendees all their outpatient clinic in Dar es Salaam – in particular
patients with PN were found to be at the risk of acquiring rodent bites on their feet; diabetic
rather than non‐diabetic patients appear to be singled out by rodents [10]. For patients with
diabetes and PN, trauma or injuries might go unnoticed until the patient finally becomes
symptomatic and presents to the diabetes clinic with an ulcer or injury that has progressed to
fulminating foot sepsis [10]. Although patients who neither take the time to take care of them-
selves and address foot care nor attend the diabetes outpatient clinic for follow up or educa-
tion are most at risk of ­developing infected foot ulcers, lack of sensation in the anaesthetic foot
 4c.6 ­Foot Infectio 55

Table 4c.3 Review of literature of outcomes amongst diabetes populations with foot
complications in sub-Saharan Africa in last two decades.

Prevalence of Amputation Mortality

Publication year Author Country Foot ulcer (%) Rate (%) (%)

2017 Awadalla H et al. Sudan 12.7

2015 Isiguzo CM et al. Nigeria 19.4 8.3
2012 Ngim NE et al. Nigeria 31 53 11
2010 Enweluzo GO et al. Nigeria 55.1 11.8
2009 Sie Essoh et al. Cote d Ivoire 31.4 46.9 16
2009 Kengne AP et al. Cameroon 13 16
2009 Mugambi N et al. Kenya 16
2006 Ndip EA et al. Cameroon 25.6
2002 Abbas ZG et al.a Tanzania 15 33 29.4
1999 Muyemba VM Kenya 26.5 55
1998 Sano D Burkina Faso 18.9 45.2 38.1
a
1995 Lester FT Ethiopia 25.5 53.4
a
References marked with an asterisk can be found in Ref. [5].

may cause ordinarily conscientious and responsible patients to be unaware of injuries sus-
tained through inappropriate or ill‐fitting footwear to walk barefoot on hot asphalt under the
midday sun or use keratolytic agents or razor blade to treat callosities. Any foot lesion, how-
ever innocuous it may appear, should never be disregarded. Ostensibly a minor lesion can
progress to an ulcer and provide an entry point for rapidly ascending infection. In a study of
patients with symptomatic peripheral neuropathy in Tanzania, non‐ulcerative sequelae
included dry skin, callosities, fungal infection or onycholysis [5].

4c.6 ­Foot Infection

Diabetic foot infections usually begin in ulcers that are sequelae of existing neuropathy,
macro‐vascular disease or certain metabolic disturbance. Such infections have been shown
to be the immediate cause of foot or leg amputation in 25–50% of patients with diabetes and
may result in death [5]. Patients in SSA communities often present to hospital only after the
onset of gangrene or during a stage of sepsis that might be intractable to conventional sup-
portive treatment. Patients with an infected ulcer often feel no pain because of neuropathy,
or may have no systemic symptoms until late in the course of the condition, medical pro-
viders often presume a degree of self‐neglect amongst affected patients. Fungal infection of
toenails or in the intertriginous areas may lead to cracked skin or fissures on the soles of the
feet. This type of infection produces relatively slight discomfort, but its real importance lies
in the fact that these lesions pave the way for the entry of microorganisms into the foot,
leading to secondary bacterial infection. It is not surprising, therefore, that foot infections
are especially common where there are no available services for follow‐up of the diabetic
56 4c The Diabetic Foot Worldwide: Sub-Saharan Africa

foot, or lesions are ignored or detected relatively late in the course of the infection after
unsuccessful home therapy, such as soaking in hot water, or application of unproven herbal
remedies prescribed by traditional healers. Foot infections of this nature culminate in the
onset of gangrene or disseminated infection with ensuing amputation of the foot or entire
limb, or death from overwhelming sepsis [5].
Deep tissue biopsy for culture and sensitivity is likely to give more useful information.
However, many microbiology services in resource‐poor countries do not have facilities to
analyse biopsy specimens on a routine basis [30, 31]. For this reason, Abbas et al. had to
look for solutions to overcome this in less‐developed countries by conducting epidemiologic
and microbiologic studies and the use of antibiotics. Use of simple bedside test Gram stain-
ing to observe microorganisms, can be done at any clinic in the countries with poor resources
[30, 31]. We looked at the utility of Gram stains in comparison with culture and sensitivity
in the management of limb ulcers in people with diabetes. We found a sensitivity of more
than 90% and that clinical outcome following the use of empirically chosen broad‐spectrum
antimicrobials (without microbiology cultures and sensitivity), in conjunction with surgical
debridement, yielded similar or better outcomes than antimicrobials chosen by antimicro-
bial susceptibility testing of pathogens isolated from deep tissue cultures [30, 31].

4c.7 ­Amputation

Gangrene and infection appear to be mostly common cited indications for foot amputation
in patients with diabetes [5]. High rates of amputation are seen across the SSA from 16 to
55% [5, 24–29, 32], (Table 4c.3). However, the true lower limb amputation rate resulting
from foot infections in SSA remains underestimated. About 10% of patients who needed
and agreed to undergo surgery died from advanced sepsis in SSA before planned surgical
procedure was actually carried out [5].

4c.8 ­Mortality

Mortality rates are high in SSA patients with diabetic foot ulcer [5, 26–29, 32], (Table 4c.3).
Abbas and colleagues ascertained clinical correlates for mortality amongst diabetic patients
with foot ulcers in Tanzania. They found that the overall mortality rate amongst patients
with foot ulcers was 29% and was significantly higher amongst patients with PAD, neurois-
chaemic, late presentation, or non‐healing ulcers. Mortality rate was 54% who presented
when gangrene has set [5]. The highest mortality rate has been documented in those who
do not undergo amputation of the relevant limb [5].

4c.9 ­Prevention

The most important intervention for the prevention of diabetic foot complication is the
education of the patient about proper foot care. Education is the most powerful tool that
SSA has which is free to the patient, and it can be effective if implemented properly. It
 4c.9 ­Preventio 57

should be an integral part of prevention programmes, simple and repetitive. It is important

that it should directed to people with diabetes and health care workers. Several education-
programmes aimed at preventing diabetic foot ulcers have been carried out and executed
successfully in both developed and developing world [3–6, 30, 31, 33–36].

4c.9.1 Step by Step Foot Project

One of these programmes is the Step by Step foot project, which was piloted and carried out
in Tanzania and India. This project showed that infection, ulceration, and limb amputation
are potentially prevented through organized foot care programmes and approaches that
encompass comprehensive, preventive strategies, including patient and staff education,
joining medical and surgical management of foot ulcers and regular follow up. Importantly
the project was found to be associated with greater than a 50% reduction in amputation rate
[3–6, 30, 31, 33–35].
Several further training Step by Step foot projects were carried out in Tanzania after the pilot
project in 2004. The first surgeon’s Step by Step foot project was also conducted in 2009. After
successful training projects done in Tanzania led to increase demand for Step by Step foot
programme to be rolled out in other countries [3–6, 30, 31, 33–35]. One of the aims was to
export the idea to other nations, and to date the model has been exported to various other
countries in Africa (Democratic Republic of Congo, Guinea, Botswana, Malawi, Kenya,
Ethiopia, Egypt, Zimbabwe, Mali, and Nigeria), as well as in India, Pakistan, and the Caribbean
(Barbados, St Lucia, St Maarten, St Kitts, and the British Virgin Islands) [3–6, 30, 31, 33–35].

4c.9.2 Train the Foot Trainer (TtFT) Project

In December 2012, a decision was made to replace the Step by Step Foot Project with a TtFT
project. The TfFT course targets health care workers from different countries in that region
to come under one roof and then disseminate the knowledge once they go home back to
their own countries. The first successful TtFT course was conducted in Brazil in 2012 with
participants from 14 countries in South America [3–6, 30, 31, 33–36]. In July 2013, the sec-
ond course was conducted in Tobago (Caribbean) with participants from 22 countries. In
February 2015 the third TtFT course was conducted in Bled, Slovenia (Central and Eastern
Europe), where 17 Eastern European countries participated. In November 2016, the fourth
TtFT course was conducted in Bangkok (Western Pacific region) and helped train health
care workers from 13 countries. Fifth edition of the TtFT was conducted in 2018 in Marrakesh,
where health care workers from 13 countries participated. Sixth edition of the TtFT was
conducted in 2020 for Meena region in Abu Dhabi and 14 countries took part in the course.
The TtFT courses are being considered in future for African and North American countries
as well [3–6, 30, 31, 33–36]. This is the only unique project which has actually started in the
developing world (Dar es Salaam, Tanzania) and been ultimately exported to the developed
world. In the author’s opinion, improvement in the field of preventive foot care and reduc-
ing amputation will only be achieved by focusing on education [3–6, 30, 31, 33–36].
Professionals need to learn the five main pillars of preventive diabetic foot, which are as
follows: (i) Regular inspection and examination of the feet and footwear, (ii) identification
of high‐risk patients, (iii) education of the high‐risk patients, relatives, friends, and health
care workers, (iv) appropriate footwear for diabetic patients, (v) treatment of non‐ulcerative
58 4c The Diabetic Foot Worldwide: Sub-Saharan Africa

pathology. By implementing these five pillars, limb amputation can be reduced by more
than 50%. Several successful preventive educational programmes have been carried out in
developed and developing countries[3–6, 30, 31, 33–36].

4c.10 ­Conclusions

Whilst it may be impossible to totally prevent foot ulceration, it is certainly feasible to

prevent the progression of small ulcers to infection, sepsis, osteomyelitis or gangrene.
Education remains the most important prevention tool in Africa and should be an inte-
gral part of preventive programme: simple and repetitive, and targeted at both health‐
care workers and patients alike. Diabetic patients must be educated on the importance
of foot care and of consulting a health care worker during the early stages of foot related
symptoms. Ultimately, success will depend on the ability of health care providers to
inculcate the motivation and self‐help that are essential for the well‐being of diabetic
patients.

R
­ eferences

1 Abbas, Z.G. (2013). The global burden of diabetic foot. In: Contemporary Management of
Diabetic Foot, 1e (ed. S. Pendsey), 24–30. JP Medical, Ltd.
2 International Diabetes Federation (2020). Diabetes Atlas, 9th edn. https://www.
diabetesatlas.org/en/2020 (Accessed 8th February, 2020).
3 Abbas, Z.G. (2013). Preventing foot care and reducing amputation: a step in right direction
for diabetes care. Diabet. Manag. 3: 427–435.
4 Abbas, Z.G. (2017). Managing the diabetic foot in resource‐poor settings: challenges and
solutions. Chronic Wound Care Manage. Res. 4: 135–142.
5 Abbas, Z.G. and Archibald, L.K. (2006). Recent International Development: Africa. In:
The Foot in Diabetes, 4e (eds. B. AJM, P. Cavanagh and G. Rayman), 379–385. Wiley.
6 Abbas, Z.G. and Archibald, L.K. (2007). Challenges for the management of the diabetic
foot in Africa: doing more with less. Int. Wound J. 4: 305–313.
7 Cavanagh, P., Attinger, C., Abbas, Z.G. et al. (2012). Cost of treating diabetic foot ulcers in
five different countries. Diabetes Metab. Res. Rev. 28: 107–111.
8 Abbas, Z.G. and Archibald, L.K. (2007). The diabetic foot in sub‐Saharan Africa: a new
management paradigm. Diabet. Foot J. 10: 128–137.
9 Morbach, S., Lutale, J., Viswanathan, V. et al. (2004). Regional variation of risk factors and
clinical presentation of diabetic foot lesions. Diabet. Med. 21: 91–95.
10 Abbas, Z.G., Lutale, J., and Archibald, L.K. (2005). Rodent bites on the feet of diabetes
patients in Tanzania. Diabet. Med. 22: 631–633.
11 Ndip, E.A., Tchakonte, B., and Mbanya, J.C. (2006). A study of the prevalence and risk
factors of foot problems in a population of diabetic patients in Cameroon. Int J Low Extrem
Wounds 5: 83–88.
12 Mugambi‐Nturibi, E., Otieno, C.F., Kwasa, T.O. et al. (2009). Stratification of persons with
diabetes into risk categories for foot ulceration. East Afr. Med. J. 86: 233–239.
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Tanzania: a contrast between African and Asian populations. Int. Wound J. 6: 124–131.
14 Jarso, G., Ahmed, A., and Feleke, Y. (2011). The prevalence, clinical features and
management of peripheral neuropathy among diabetic patients in TikurAnbessa and St.
Paul’s Specialized University Hospitals, Addis Ababa, Ethiopia. Ethiop. Med. J. 49: 299–311.
15 Owolabi, M.O. and Ipadeola, A. (2012). Total vascular risk as a strong correlate of severity
of diabetic peripheral neuropathy in Nigerian Africans. Ethn. Dis. 22: 106–112.
16 Kuate‐Tegueu, C., Temfack, E., Ngankou, S. et al. (2015). Prevalence and determinants of
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108–112.
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18 Awadalla, H., Noor, S.K., Elmadhoun, W.M. et al. (2017). Diabetes complications in
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prevalence in rural black South Africans. S. Afr. Med. J. 97: 285–288.
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21 Mwebaze, R.M. and Kibirige, D. (2014). Peripheral arterial disease among adult diabetic
patients attending a large outpatient diabetic clinic at a national referral hospital in
Uganda: a descriptive cross sectional study. PLoS One 9 https://doi.org/10.1371/journal.
pone.0105211.
22 Konin, C., EssamN’loo, A.S., Adoubi, A. et al. (2014). Peripheral arterial disease of the
lower limbs in African diabetic patients: ultrasonography and determining factors. J. Mal.
Vasc. 39: 373–381.
23 Codjo, H.L., Adoukonou, T.A., Wanvoegbe, A. et al. (2016). Prevalence of peripheral artery
disease among diabetics in Parakou in 2013. Ann. Cardiol. Angeiol. 65: 260–264.
24 Kengne, A.P., Djouogo, C.F., Dehayem, M.Y. et al. (2009). Admission trends over 8 years for
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Wounds 8: 180–186.
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26 Enweluzo, G.O., Giwa, S.O., Adekoya‐Cole, T.O. et al. (2010). Profile of amputations in
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27 Ngim, N.E., Ndifon, W.O., Udosen, A.M. et al. (2012). Lower limb amputation in diabetic foot
disease: experience in a tertiary hospital in southern Nigeria. Afr. J. Diabet. Med. 1: 13–15.
28 Isiguzo, C.M. and Jac‐Okereke, C. (2015). Diabetic foot ulcer – 12 months prospective
review of pattern of presentation at Enugu Stat university of technology teaching hospital,
Parklane, Enugu: a basis for diabetic foot clinic? Niger J Med 24: 125–130.
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30 Atun, R., Davies, J.I., Gale, E.A.M. et al. (2017). Diabetes in sub‐Saharan Africa: from
clinical care to health policy. Lancet Diabetes Endocrinol. 5: 622–667.
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in the management of limb ulcers in persons with diabetes. Int. Wound J. 9: 677–682.
32 Muyember, V.M. and Muhinga, M.N. (1999). Major limb amputation at a provincial general
hospital in Kenya. East Afr. Med. J. 76: 163–166.
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Tanzania: a model for improving patient outcomes in less‐developed countries. Int. Wound J.
8: 169–175.
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Rev. Endocrinol. Metab. 10: 425–434.
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based management. In:1e (eds. R. Hinchliffe, M. Thompson, N. Schaper, et al.), 24–30.
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of the ‘Train the Foot Trainer’ program: the diabetic foot. Journal 20: 71–76.
 61

4d

Burden of Diabetic Foot Disease in Brazil

Hermelinda C. Pedrosa1 and Luciana R. Bahia2
1
Brazilian Society of Diabetes – Government Relations Advisor 2020-202, Endocrinology Unit/FEPECS Research and
Diabetic Foot Center, Brasilia, Brazil; Worldwide Initiatives for Diabetes Education
2
State University of Rio de Janeiro, Epidemiology, Public Health and Health Economics Department of the Brazilian Society
of Diabetes, Brazilian Health Technology Assessment Institute, Brasilia, Brazil

The incidence of diabetic foot ulceration (DFU) is increasing due to the high prevalence of
diabetes mellitus (DM) worldwide and longer life expectancy of diabetic patients. The
annual incidence of 2–4% in developed countries is probably higher in developing coun-
tries because of differences in socioeconomic conditions, type of footwear and standards of
foot care [1,2]. The International Diabetes Federation (IDF) estimates that DFU develops in
9.1–26.1 million people with DM annually [3] and every year, over one million people lose
part of their lower limbs as a consequence of the disease complications. This translates into
the estimate that every 20 seconds a lower limb is lost due to DM [2].
In Brazil, the population has the right to medical assistance through the Unified Public
Health System/ Sistema Único de Saúde (SUS) and 70% depend exclusively on it. SUS
plays a fundamental role in the prevention and treatment of chronic diseases and it is the
family health strategy/ Estratégia de Saúde da Família (ESF) team’s responsibility to iden-
tify people at risk, to diagnose and to perform the periodic integral care of individuals
with DM [4]. ESF teams are composed by a General Practioner, a generalist nurse, a nursing
assistant, and community health agent. The majority of diabetic patients are treated in
­primary care facilities but scarce health care providers (HCP) are properly trained to
screen, evaluate and treat diabetic foot problems.
Pioneer initiatives, such as Saving the Diabetic Foot Project by Pedrosa et al., were imple-
mented in the 1990s and lasted until the early 2000s under the support of the Ministry of
Health [5]. Despite the positive spread of over 60 outpatient DFU clinics set up in the coun-
try, which caused an impressive impact in the international community [1], the Project was
discontinued along the years. Sadly, it did not turn into a formal health policy and DFU still
is an incredible high cost to the public health system [6].
During the past 30 years there has been a significant increase of evidence‐based research
on DFU, national and international meetings, and several interest group formations in
many countries including Brazil, in order to improve the situation of diabetic foot [1].

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
62 4d Burden of Diabetic Foot Disease in Brazil

Unfortunately, the same is not true in developing countries concerning data availability: a
recent systematic review estimated a global prevalence of 6.3%, but Latin America coun-
tries were not included due to absence of English language published studies [7].
Data from a National Health Survey (2013 estimated 5–5.8% of people with DM to had foot
injuries and 0.7–2.4% suffered limb amputation [8], despite the possible underestimation of
real situation as information has been obtained through interviews (self‐reported diagnoses).
Some of the available Brazilian data derives from regional surveys. Vieira‐Santos et al.
enrolled 1374 patients in six primary care ESF units in the northeast of Brazil and demon-
strated both the prevalence of DFU and amputations to be 9 and 2.3%, respectively [9].
The cross sectional Brazupa Study (2012–2014) was conducted amongst 19 specialized
diabetic centres with 1455 patients [10], as it shows change to as demonstrated in
Figure 4d.1. DFU individuals had longer DM duration (17.2 ± 9.9), poorer glycemic
­control (HbA1c 9.23 ± 2.03); ulcer independent risk factors were male gender, smoking,
neuroischemia, region of origin (South/southeast), retinopathy and absence of vibration
perception whilst amputation risks were male gender, DM2, ischemia, previous ulcer
(25.3%) and also absence of vibration perception. Amputation history was found in 13.7%
of patients (17.3% major, 5.3% ≥ 2 previous amputations).
The typical patient with a DFU in the Eurodiale Study (European Study Group on Diabetes
and the Lower Extremity) [11] was an older male (mean age of 65 years), with long‐standing
diabetes (70% > 10 years), poor health status (33% had a disabling co‐morbidity such as
visual impairment, heart disease, renal failure) or poor mobility that required assistance for
personal care. Nearly one half of patients had a HbA1c level > 8.4%.
Few studies on the economic burden have been undertaken in Brazil, and the few studies
focused on hospital costs and inadequate outpatient management [12–14]. Such ­information
is important for public health policymakers to advocate implementation of prevention and
treatment recommendations. In a prospective cost study, Rezende et al. [6] verified that
­government hospitalization reimbursement was seven times lower than the estimate
­provided by a micro‐costing approach [6]. Recently, Toscano et al. [15] assessed, for the first
time, ­outpatient and hospital overall economic DFU burden: annual direct medical cost
estimate provided was $361 million (International dollars, 2014), which denotes 0.31% of
total public health expenses for this period.
A Brazilian multicentre outpatient study [16] analysed 2233 DM2 patients and verified
that foot examination was only performed in 58% [16]. Similar data was found in DM1
individuals [17]: foot exam had the highest clinical registration failure compared to other
parameters (eye exam, microalbuminuria, and HbA1c).
Education and multi‐disciplinary team approach can reduce foot complications and
amputations significantly [1, 2, 5]. The Brazilian Diabetes Society has rescued the Saving
the Diabetic Foot Project [5] in 2012 during the Train the Foot Trainers Course SACA IDF
Region [18], following the Step by Step Project strategy [19]. Since then, nearly 1.000
Healthcare Providers (Figure 4d.2) have been trained on foot exam and management [20].
Despite efforts done by the Brazilian Society of Diabetes, it is crucial that the Ministry of
Health embraces this approach and shall turn it into a state health policy. Otherwise, the
chances of success will be missed. Moreover, identifying DFU costs is also of paramount
importance to mobilize society, inform policy makers, and help to determine the cost‐effec-
tiveness of interventions for disease prevention and control, and to monitor the impact of
the implementation of any intervention.
 4d Burden of Diabetic Foot Disease in Brazil 63

RORAIMA AMAPA

AMAZONAS MARANHAO RIO GRANDE

PARA CEARA DO NORTE

PARAIBA
ACRE PIAUI
PERNAMBUCO
TOCANTINS ALAGOAS
RONDONIA BAHIA
SERGIPE
MATO GROSSO
BRASILIA

GOIAS MINAS
GERAIS
MATO ESPIRITO SANTO
GROSSO
DO SUL
RIO DE JANEIRO

PARANA SAO PAULO

SANTA CATARINA

RIO GRANDE
DO SUL

Figure 4d.1 Brazupa Study: 19 specialized centres of Brazil enrolled 1455 patientes with diabetes
and lower limb problems including states from northern, southeast, middlewest and south of the
country [10].
64 4d Burden of Diabetic Foot Disease in Brazil

Macapá

NORTE Fortaleza

Campina Grande

NORDESTE
Recife
CENTRO
OESTE
Salvador

Brasília SUDESTE
Belo Horizonte
Goiânia

Rio de Janeiro

Both courses São Paulo

Basic course
No course Curitiba
SUL
Joinville
Total attendees:
982 HCP
Porto Alegre

Figure 4d.2 Step by Step training courses in Brazil under the support of the Brazilian Diabetes
Society (SBD): basic and advanced courses from 2013 to 2018 – nearly 1000 Health Care
Professionals (HCP) have been trained on the management of DFU [18]. In 2019, six more editions
of Step by Step were held in other six cities (Brasilia, Recife, Campinas, São Paulo, Manaus,
Fortaleza) and the current number of HCP has surpassed 1200.

­References

1 Markakis, K., Bowling, F.L., and Boulton, A.J.M. (2016). The diabetic foot in 2015: an
overview. Diabetes Metab. Res. Rev. 32 (Suppl. 1): 169–178.
2 Bakker, K., Apelqvist, J., Lipsky, B.A. et al. (2016). The 2015 IWGDF guidance documents on
prevention and management of foot problems in diabetes: development of an evidence‐
based global consensus. Diabetes Metab. Res. Rev. 32 (Suppl. 1): 2–6.
3 Diabetes Atlas (7th edn), (2017). http://www.diabetesatlas.org.
4 Departamento de Atenção Básica – Ministério da Saúde. http://www.foa.unesp.br/home/
pos/ppgops/portaria‐n‐2436.pdf.
5 Pedrosa, H.C., Leme, L.A.P., Novaes, C. et al. (2002). The diabetic foot in South Ametica:
progress with the Brazilian save the diabetic foot project. Int. Diabetes Monit. 16: 11–17.
6 Rezende, K.F., Ferraz, M.B., Malerbi, D.A. et al. (2009). Direct costs and outcomes for in
patients with diabetes mellitus and foot ulcers in a developing country: the experience of the
public health system of Brazil. Diabetes Metab. Syndr. Clin. Res. Rev. 3 (4): 228–232.
 References 65

7 Zhang, P., Lu, J., Jing, Y. et al. (2016). Global epidemiology of diabetic foot ulceration: a systematic
review and meta‐analysis. Ann. Med. 49: 106–116. https://doi.org/10.1080/07853890.
2016.1231932.
8 BRASIL. IBGE. Pesquisa Nacional de Saúde (2013). (National Health Survey 2013). https://
ww2.ibge.gov.br/home/estatistica/populacao/pns/2013/default.shtm.
9 Vieira‐Santos, I.C., Vieira de Souza, W., Freese de Carvalho, E. et al. (2008). Prevalência de
pé diabético e fatores associados nas unidades de saúde da família da cidade do Recife,
Pernambuco, Brasil, em 2005. Cadernos de Saúde Pública 24: 2861–2870.
10 Parisi, M.C., Moura Neto, A., Menezes, F.H. et al. (2016). Baseline characteristics and risk
factors for ulcer, amputation and severe neuropathy in diabetic foot at risk: the BRAZUPA
study. Diabetes Metab. Res. Rev. 8: 25.
11 Schaper, N.C. (2012). Lessons from Eurodiale. Diabetes Metab. Res. Rev. 28 (Suppl 1): 21–26.
12 Haddad, M.C., Bortoletto, M.S.S., and Silva, R.S. (2010). Amputação de membros inferiores
de portadores de diabetes mellitus: Análise dos custos da internação em hospital público.
Ciência, Cuidado e Saúde 9: 107–113.
13 Oliveira, A.F., De Marchi, A.C.B., Leguisamo, C.P. et al. (2014). Estimativa do custo de
tratar o pé diabético, como prevenir e economizar recursos. Cien. Saude Colet. 19:
1663–1671.
14 Milman, M.H.S.A., Leme, C.B.M., Borelli, D.T. et al. (2001). Pé diabético: Avaliação da
evolução e custo hospitalar de pacientes internados no conjunto hospitalar de Sorocaba.
Arq. Bras. Endocrinol. Metabol. 45: 447–451.
15 Toscano, C.M., Sugita, T.H., Rosa, M.Q.M. et al. (2018). Annual direct medical costs of
diabetic foot disease in Brazil: a cost of illness study. Int. J. Environ. Res. Public Health 15:
89. https://doi.org/10.3390/ijerph15010089.
16 Gomes, M.B., Gianella, D., Faria, M. et al. (2006). Prevalence of patients with diabetes type
2 within the targets of care guidelines in daily clinical practice: a multicenter study of type
2 diabetes in Brazil. Rev. Diabet. Stud. 3: 73–78.
17 Gomes, M.B., Cobas, R., Matheus, A.S. et al. (2012). Regional differences in clinical care
among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group.
Diabetol. Metab. Syndr. 4: 44. https://doi.org/10.1186/1758‐5996‐4‐44.
18 Train‐the‐Foot‐Trainer | IWGDF. iwgdf.org/ttft/.
19 Pendsey, S. and Abbas, Z.G. (2007). The step‐by‐step program for reducing diabetic foot
problems: a model for the developing world. Curr. Diab. Rep. 7 (6): 425–428.
20 International Perspectives on Treatment of the Diabetic Foot—A Walk Across the World.
www.diabetes.org.
 67

4e

Diabetic Foot in Romania and Eastern Europe

Norina Alinta Gâvan1 and C. I. Bondor2
1
Association for Podiatry, Cluj-Napoca, Romania
2
Iuliu Hațieganu University of Medicine and Pharmacy Cluj-Napoca, Department of Medical Informatics and Biostatistics,
Cluj-Napoca, Romania

4e.1 ­Introduction

According to the figures published in the 8th Edition of the International Diabetes
Federation (IDF) Diabetes Atlas, in 2017 there were 58 million people with diabetes in
Europe and the projection for 2045 is to reach 67 million [1].
The major objective for European diabetology established by IDF Europe Working Group
in 1989, was a reduction in the amputation frequency by 50% in 5 years [2]. Despite this
common goal, the epidemiological dynamics of ulceration in people with diabetes has
shown an increasing trend.

4e.2 ­The Aim

The aim of this chapter is to present the situation of the diabetic foot in Romania and
Eastern Europe. A second objective is to show a positive change in the awareness of this
continuous challenge that is diabetic foot and its complications of health care professionals
and authorities from this geographic area.

4e.3 ­Diabetic Foot in Romania

Similar to the global trends, Romania also reported an increase in the number of patients
diagnosed with diabetes in the recent years. According to an epidemiological study per-
formed in Romania between 2012 and 2014, the overall prevalence of diabetes adjusted for
age and gender was 11.6% [3], the prevalence estimated by IDF for 2017 increased to 12.5%
of the adults [1].

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
68 4e Diabetic Foot in Romania and Eastern Europe

For foot ulceration, the prevalence reported by epidemiological studies was 3.2% in
patients with type 1 diabetes mellitus and 3.8% in patients with type 2 diabetes [4].
Information on the incidence of diabetes‐related amputations is also available. Based on
data from 2010 crude incidence of diabetes‐related amputations/105 persons/year in gen-
eral population was 26 and crude incidence of diabetes‐related amputations/105 persons/
year in patients with diabetes was 779 [5]. An overall increase in the lower limb amputation
rates was observed for the patients with diabetes between 2006 and 2010. Whilst the rates
of amputations in type 1 diabetes decreased with 27.7% in 5 years, the rates of amputations
in type 2 diabetes increased by 104.6% [6]. Also, the amputation statistics changed in
Romania between 2006 and 2010. The minor to major amputation ratio increased from 2.38
to 2.95, indicating more minor amputations.
In 2012, the quality of life (QoL) in diabetic neuropathy patients was analysed in a cross‐sec-
tional survey, using the Norfolk QoL‐Diabetic Neuropathy Scale. The objective was to expand
research on the diabetic foot and to provide an update on the number of foot ulcers found in
Romania. Of the 21 174 patients included in this analysis, 14.9% reported a history of foot ulcers
and 3.6% reported an amputation. The percentage of patients with diabetic neuropathy and a
history of foot ulcers increased with age; the lowest percentage was observed in the 20–29‐year
age group (6.6%) and the highest in the 80–89‐year age group (17.7%) [6].
Despite improvements in the standard of care of the diabetic foot in Romania, foot ulcers
and amputations were reported at young ages in the active population, with consequent
high direct and indirect costs. A possible explanation might be the variation of the delivery
of preventative measures and foot care at local level; currently, specialized clinicians in
diabetic foot care are available only in large hospitals in big cities [5]. This may have led to
limited access to specific education for a large number of diabetic patients, with conse-
quences on level of health literacy, on understanding and implementing preventative
measures, and on referral to the clinicians in early stages of the pathology. A study assess-
ing the impact of time between the onset of symptoms of diabetes/its complications and
the visit to the physician found a significant relationship between the occurrence of self‐
reported neuropathy or foot ulcers, gangrene or amputations and the time period between
the occurrence of symptoms and the consult with a clinician [7]. ‘The odds of self‐reported
neuropathy and foot ulcers were significantly higher in those who delayed seeking medical
care for more than one month after the onset of symptoms of diabetes or its complications
as compared to those presenting in first month from symptoms onset and increased in
parallel with the time between the symptoms onset and the physician visit’ [7]. Notably,
the frequencies of gangrene and amputations were twofold higher in those who sought
medical care after two years from symptoms onset [7]. In conclusion, early detection of
diabetic neuropathy/its complications, as early as within one month from symptom onset,
is needed to prevent foot ulcers. In Romania, data are alarming − only 25% of the patients
who completed the questionnaires visit the clinicians in the first month after the onset of
the symptoms [7].
These results support the need to implement easily accessible educational programmes
in diabetes and diabetic foot and its complications. In Romania, two non‐governmental
and non‐profit, professional associations are involved in these activities − the Society for
Diabetic Neuropathy‐NeuRODiab, founded in 2012, and the Association for Podiatry,
founded in 2015.
 4e.3 ­Diabetic Foot in Romani 69

The Society for Diabetic Neuropathy‐NeuRODiab declared as main purpose ‘to carry out
medical, scientific, research, and professional training activities in the medical field, of
­edification, expansion of scientific material base for the development and study of diabetic
neuropathy in Romania, of promotion and support the integration (medically) of Romania in
the European Union, as well as of providing medical services’ [8]. The members of NeuRODiab
ensure the persons with diabetes mellitus affected by diabetic neuropathy stand and fight the
disease and to prevent the diabetic foot syndrome. They believe that it is important to facilitate
the dialogue and to connect patients and their families with the diabetologist, neurologist,
family physician, surgeon, psychologist, and nurse [8]. NeuRODiab members organize an
annual congress and an annual summer school for young physicians to inform healthcare
professionals about knowledge and evidence in this field, including diagnosis of diabetic neu-
ropathy, a difficult issue due to the lack of accepted standards [8, 9]. Additionally, NeuRoDiab
has expressed its wish to be actively involved in the studies in the area of diabetic neuropathy
and its complications to reduce its social and economic implications [8].
Although most foot amputations in people with diabetes can be avoided, in Romania, the
number of such procedures is a concern. The development of podiatry is the best solution for
the healthcare system in Romania in relation to the diabetic foot syndrome [10]. The
Association for Podiatry declares its mission “to increase the awareness of the only medical
branch (i.e. podiatry) with the potential to reduce amputations in diabetes”. It was shown that
the inclusion of a podiatrist in the diabetic foot care team could reduce the amputation rate
by 85% [11]. This is a critical cost issue and prevention is cheaper than the treatment [12, 13].
In the current national context, training of health care professionals (nurses, physiother-
apists and even physicians) and the establishment of podiatry as a medical profession
should be a priority as it is evidence‐based [14]. The introduction of this medical profession
or medical specialty in Romania is prerequisite for ensuring adequate and effective care of
foot problems in general population and especially in people with diabetes to prevent
amputation [15]. These represent the main objectives of the Association for Podiatry.
Because the importance of the diabetic foot syndrome is underestimated: another objective
of the Association for Podiatry is to underline the impact of social and economic costs of
diabetic foot in the Romanian healthcare system by implementing the future local studies
[16]. The Association for Podiatry organizes an annual congress, an annual summer school
and numerous meetings and courses to inform health care professionals and authorities
about these objectives [16]. Education can reduce the frequency of diabetic neuropathy
foot complications [17].
Based on the number of published articles found in the medical literature the interest for
diabetic foot has increased in Romania in the last period. We searched in PubMed for
­studies published on the diabetic foot in Romania and we found that of 21 total articles on
this topic, 17 were in the past 10 years.
As a concluding remark, despite the interest for diabetic foot, and despite the strong rec-
ommendations of 2015 IWGDF guidance, in Romania the implementation of the recom-
mendations was very poor. Local authorities did not have any methods to motivate or
control the healthcare professionals as:‐ (i) diabetic foot care is still poorly organized in the
public healthcare system due to the lack of podiatry and the lack of a real multidisciplinary
team, (ii) the prevention of diabetic foot is not reimbursed and (iii) podiatry is not recog-
nized as a profession.
70 4e Diabetic Foot in Romania and Eastern Europe

4e.4 ­Diabetic Foot in Eastern Europe

The term ‘Eastern Europe’, mainly refers to the eastern part of the European continent and
is based on geographical and geopolitical principles.
According to the figures published in the 8th edition of the IDF Diabetes Atlas, the
national prevalence of diabetes in these countries from Eastern Europe were: Albania – 12%;
Czech Republic – 9.6%; Slovak Republic – 10.7%; Hungary – 9.6%; Bulgaria – 8.2% and
Russian Federation – 8.1% [1].
We found limited data on the prevalence of diabetic foot, respectively ulcerations and/or
amputations in the above‐mentioned countries. For example, for Czech and Slovak
Republics, searching the keyword ‘diabetic foot’ in PubMed we found a total number of 60
(44 written in English) articles, of which 37 were published by Czechoslovakian authors or
from the Czech and Slovakian Republics in the last 10 years, but only four covered our
topic of interest. A study carried out in the Czech Republic between 2010 and 2013 and
analysing data from General Health Insurance Company on all people with a record of
diabetes or any prescribed antidiabetic therapy, reported 44 259 cases of foot syndrome/
year and 10 125 amputations/year of [18]. Based on these figures and Czech Republic pop-
ulation numbers from World Bank [19], estimated total crude incidence of foot syndrome
was 421.6/105, and crude incidence of amputation was 96.5/105. The rate of major amputa-
tions was relatively stable between 2004 and 2015, representing 3.2% of total amputations
in 2004–2006 and 5.1% of total amputations in 2013–2015 [20]. Two studies underlined that
a patient with diabetic foot syndrome should be followed by a specialized team of experts,
led by diabetologists and podiatrists, because the complexity of the causes underlying this
condition [21, 22]. The only study on diabetic foot identified as originating from Slovakia,
was carried out between 1993 and 1995 and reported a prevalence of ulceration of 2.5% and
of amputation of 0.9%. The same study mentioned an incidence of ulceration of 0.6% and
of amputation of 0.6% [23].
When we repeated the search for articles on diabetic foot with authors originating from
Hungary, we found 18 articles, of which 9 were published in the last 10 years and only 1
covered the diabetic foot topic. A large study on Hungarian patients employing administra-
tive health care data showed that the incidence of lower extremity major amputations did
not change significantly between 2004 and 2012. The crude incidence of lower major limb
amputations was 42 /105 persons in the general population and 318/105 persons in diabetic
population. More than 50% of patients with major amputation were diabetic. The risk of
amputation in the diabetic population was 15 times higher as compared to non‐diabetic
patients. The high proportion (70%) of amputations at thigh level, the ratio of primary/
major amputations (72%), the high crude incidence of amputation in patients with prior
lower limb revascularization (3998/105), shows that the situation is also unsatisfactory in
Hungary [24].
For Russia, we found 48 articles published by Russian authors or from Russian Federation,
of which 39 in the last 10 years. Of these only two (one written in English) articles covered
our topic of interest. One of these articles was that of Kalashnikova in 2014 which presents
a study of 48 978 persons with type 2 diabetes and which was performed between 1999 and
2011. In this study they found a prevalence rate of type 2 diabetes of 1590/105 persons.
The frequencies of complications causing lower limb disorders were 7.8% of diabetic
  ­Reference 71

polyneuropathy of the lower limbs, 3.2% of diabetic macroangiopathy of the lower limbs,
0.9% of diabetic foot syndrome, 0.08% of ischemic form, 0.1% of neuropathic form, 0.1% of
mixed form, 0.04% without ulceration, 0.06% with ulceration, 0.15% amputation (within
the foot, but more than one finger), and 0.12% amputation (at the level of the lower leg and
higher). They reported a declining trend of amputations in the studied period [25]. Another
study mentions 22 000 amputations in 2009 in the whole Russian Federation (2009 population
were 142.8 million), which gave a crude incidence of 15/105 persons [26, 27].
For Bulgaria and Albania, we found no studies published on the diabetic foot topic in the
past 10 years.

4e.5 ­Conclusions

The majority of the studies cited here identified diabetic foot problems as a source of suf-
fering for people and of additional social costs [4–6, 8, 24, 25]. Most of the studies reported
alarming statistics on diabetic foot complications, and underline the need for an increase
in follow‐up and training activities, as well as for an increased access for diabetic patients
to healthcare providers specialized in foot care [4–6, 24–26]. There is also a need to
increase awareness on diabetic foot in Eastern Europe; if in some countries a growing
interest in this topic can be seen; in others we cannot say that there is any interest for
diabetic foot syndrome.
The aim of the professional organizations acting in the field of diabetes is to continue to
follow the frequency of foot ulcers and amputations in diabetic patients [8, 16]. The general
opinion in Eastern Europe is that investing in appropriate diabetic foot care guidance under
conditions established by medical evidence, and pursuing well‐established objectives is
amongst the most cost‐effective healthcare expenditure [8, 22].

­References

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Belgium: International Diabetes Federation; [cited 2015 Jun 23]. www.diabetesatlas.org.
2 World Health Organization (1992). Regional Office for Europe, International Diabetes
Federation. European Region. Diabetes care and research in Europe: The St Vincent
Declaration action programme. Implementation document. Giornale Italiano di
Diabetologia, 12 (Suppl 2): 4–9.
3 Mota, M., Popa, S.G., Mota, E. et al. (2016). Prevalence of diabetes mellitus and prediabetes
in the adult Romanian population: PREDATORR study. J. Diabetes 8: 336–344.
4 Vereşiu, I.A., Negrean, M., and Niţă, C. (2003). Simptomele şi/sau semnele de neuropatie
diabetică autonomă sunt prezente frecvent la pacienţii cu ulceraţii ale picioarelor. In:
Proceedings of the 29th National Congress of the Romanian Society of Diabetes, Nutrition
and Metabolic Diseases; 14–17 May; Craiova: Acta Diabetol Rom;29:p. 126.
5 Vereşiu, I.A., Iancu, S.S., and Bondor, C. (2015). Trends in diabetes‐related lower extremities
amputations in Romania‐A five year nationwide evaluation. Diabetes Res. Clin. Pract. 109:
293–298.
72 4e Diabetic Foot in Romania and Eastern Europe

6 Bondor, C.I., Veresiu, I.A., Florea, B. et al. (2016). Epidemiology of Diabetic Foot Ulcers
and Amputations in Romania: Results of a Cross‐Sectional Quality of Life Questionnaire
Based Survey. J. Diabetes Res. [serial online]. 2016 [cited 13 Feb 2018]; 2016:5439521.
Hindawi. https://www.hindawi.com/journals.
7 Gavan, N.A., Veresiu, I.A., Vinik, E.J. et al. (2016). Delay between Onset of Symptoms and
Seeking Physician Intervention Increases Risk of Diabetic Foot Complications: Results of a
Cross‐Sectional Population‐Based Survey. J Diabetes Res [serial online]. 2016 [cited 13 Feb
2018]; 2016:1567405. Hindawi. https://www.hindawi.com/journals.
8 NeuRoDiab. [About Society for Diabetic Neuropathy. Education. Events. Awards.]
[Internet]. [cited 2018 jan 6]. www.neurodiab.org. Romanian.
9 Bowling, F.L., Rashid, S.T., and Boulton, A.J. (2015). Preventing and treating foot
complications associated with diabetes mellitus. Nat. Rev. Endocrinol. 11: 606–616.
10 Nason, G.J., Strapp, H., Kiernan, C. et al. (2013). The cost utility of a multi‐disciplinary foot
protection clinic (MDFPC) in an Irish hospital setting. Ir. J. Med. Sci. 182: 41–45.
11 Krishnan, S., Nash, F., Baker, N. et al. (2008). Reduction in diabetic amputations over
11 years in a defined U.K. population: benefits of multidisciplinary team work and
continuous prospective audit. Diabetes Care 31: 99–101.
12 Armstrong, D.G., Boulton, A.J.M., and Bus, S.A. (2017). Diabetic foot ulcers and their
recurrence. N. Engl. J. Med. 376: 2367–2375.
13 Game, F.L. (2018). Local Management of Diabetic Foot Ulcers, dressings and other local
treatments. In: The Diabetic Foot Syndrome. Front Diabetes, vol. 26 (eds. A. Piaggesi and
J. Apelqvist), 200–209. Basel: Karger.
14 International Diabetes Federation (2017). Clinical Practice Recommendation on the
Diabetic Foot: A guide for health care professionals [e‐book]. International Diabetes
Federation; [cited 2018 jan 6]. IDF Online Library.
15 Bus, S.A., van Deursen, R.W., Armstrong, D.G. et al. (2016). International working group
on the diabetic foot. Footwear and offloading interventions to prevent and heal foot ulcers
and reduce plantar pressure in patients with diabetes: a systematic review. Diabetes Metab.
Res. Rev. 32 (Suppl 1): 99–118.
16 Association for Podiatry. [Events] [Internet]. [cited 2018 Jan 6]. www.podiatrie.ro.
Romanian.
17 Baba, M., Duff, J., Foley, L. et al. (2015). A comparison of two methods of foot health
education: the Fremantle diabetes study phase II. Prim. Care Diabetes 9: 155–162.
18 Piťhová, P., Honěk, P., Dušek, L. et al. (2015). Incidence of amputations among patients
with diabetes mellitus in the Czech Republic from 2010 to 2014. Vnitr. Lek. 61 (Suppl 3):
3S21–3S24.
19 World Bank Group (2017). Czech Republic population [Internet]. Sept [cited 2018.Jan.8].
www.worldbank.org.
20 Fejfarová, V., Jirkovská, A., Petkov, V. et al. (2016). Has been changed numbers and
characteristics of patients with major amputations indicated for the diabetic foot in our
department during last decade? Vnitr. Lek. 62: 969–975.
21 Olsovský, J. (2010). Comprehensive care for diabetic patients with diabetic foot syndrome.
Vnitr Lek. 56: 347–350.
22 Jirkovská, A. (2011). Adherence to the international guidelines on the treatment of diabetic
leg syndrome – options available in the Czech Republic. Vnitr. Lek. 57: 908–912.
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23 Vozar, J., Adamka, J., Holeczy, P. et al. (1997). Diabetics with foot lesions and amputations
in the region of Horny Zitmy Ostrov 1993–1995. Diabetologia 40 (S1): A46.
24 Kolossváry, E., Ferenci, T., Kováts, T. et al. (2015). Trends in major lower limb amputation
related to peripheral arterial disease in Hungary: a Nationwide study (2004–2012). Eur. J.
Vasc. Endovasc. Surg. 50: 78–85.
25 Kalashnikova, M.F., Suntsov, Y.I., Belousov, D.Y., and Kantemirova, M.A. (2014). Analysis
of epidemiological indices of type 2 diabetes mellitus in the adult population of Moscow.
Сахарный диабет 17 (3): 5–16.
26 Clark, F. (2015). Russia’s gaps in diabetes control. Lancet 385: 2033–2034.
27 World Bank Group (2017). Russian population [Internet]. [cited 2018.Jan.6]. www.
worldbank.org.
 75

4f

Diabetic Foot Worldwide: Pacific Region

Shigeo Kono
WHO-collaborating Centre for Diabetes Treatment and Education, National Hospital Organization, Kyoto Medical Center, Japan

The Pacific region has the largest population and territories. The International Diabetes
Federation (IDF) reported that the Western Pacific region (WPR) has the most number of
people with diabetes amongst all seven regions in the world and will continue to be the one
with the most by 2045 [1]. The WPR includes China with largest number of people with
diabetes as well as Pacific countries with the highest prevalence rates [2]. The WPR coun-
tries are scattered around Pacific Ocean from Oceania to East Asia, being diverse in many
aspects from climate, genetics, ethnicity, lifestyle, socioeconomic status and availability of
medical service. The number of diabetic foot lesions and consequent amputations is
increasing in the WPR. However, there are very few population‐based studies on diabetic
foot in the Pacific Region that is mainly from high‐income countries [3–5] and therefore,
much of the current situation of diabetic foot is still unknown.
With a few exceptions, the WPR lacks foot care specialists such as podiatrists or chiropo-
dists and there is much ignorance amongst those medical staff as to how to identify and
educate those at risk and treat those who have problems.
The diabetic foot care project and the multidisciplinary approach has been set up and
shown to be successful in reducing the amputation rate, especially major amputation rate
in some WPR countries [4–7]. A hospital in Thailand reported an 80% healing rate [6] and
a study from Queensland Australia showed decrease in total amputation by 40.0% [4].
However, the rest of the low‐resource countries are left behind from the benefit of a high‐
quality footcare service and a well‐coordinated team approach. In lower‐income countries,
a large number of people with diabetes neglect foot care, and seek medical advice only after
serious diabetic foot infection occurs.
To improve the situation of diabetic foot in the WPR, the Kyoto Foot Meeting Project and
IDF‐WPR Diabetic Foot Care Project have been launched since 2006 and 2011 respectively.
At these annual meetings, the representatives from WPR countries such as Australia,
Cambodia, China, Fiji, Indonesia, Japan, Malaysia, Mongolia, Philippines, Taiwan,
Thailand, and Vietnam collected clinical data on diabetic foot from their countries and
gathered together with invited experts from Europe and/or US to discuss the diabetic foot
problems in the WPR.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
76 4f Diabetic Foot Worldwide: Pacific Region

By analyzing these regional data, we found that the characteristics of diabetic foot
patients in the WPR are much different in some points from those reported other regions.
Regarding diabetic foot patients in the WPR, we found that (i) shorter duration of diabe-
tes after diagnosis is common, (ii) males are not predominant in some countries, especially
lower‐income countries, (iii) the bacterial profile and its sensitivity to antibiotics is much
more complicated because antibiotics are readily accessible without prescription and (iv)
foot trauma often occurs inside the house.
As the number of the people with peripheral arterial disease (PAD) is gradually increas-
ing in the WPR [8], ischaemic foot problems are becoming more common in the WPR,
especially in higher‐income countries [9].
In 2016, the IDF‐WPR diabetic foot care project was adopted by the Asian Association for
the Study of Diabetes (AASD) diabetic foot care project. In 2017, based upon these regional
data, we announced the following seven recommendations on the management of diabetic
foot in WPR for the WPR healthcare providers at the annual meeting of AASD, Nagoya, Japan.
Recommendations: To improve the management of Diabetic Foot Disease in the WPR
●● Educate about preventive foot‐care (especially knowledge, self‐care, and footwear) aimed
at patients and health care providers (HCPs)
●● Raise HCP skills in the screening for neuropathy and PAD at earlier stage, to help pre-
vent progression to sensory‐loss and critical limb ischaemia
●● Raise HCP skills in assessing pre‐ulcerative lesions and ulcers, including precipitating
and predisposing factors
●● Raise HCP skills in managing diabetic foot infection (DFI)
●● Isolation of pathogens; sensitivity testing to antibiotics essential in treating most DFI
(especially limb‐threatening)
●● Raise skills in DFU wound management, debridement, pressure‐offloading, and in sur-
gical revascularization and orthopaedic treatments
●● Organize networks/systems inside the country for timely and progressive (from lower to
higher level multidisciplinary services) referral and for hospitalization for DFU
●● Ensure periodic, appropriate follow‐up management for DFU patients to ensure DFU
resolution and to prevent recurrence

R
­ eferences

1 IDF (2019). IDF Diabetes Atlas 9e. https://diabetesatlas.org/upload/resources/2019/

IDF_Atlas_9th_Edition_2019.pdf
2 Chan, J.C., Cho, N.H., Tajima, N. et al. (2014). Diabetes in the Western Pacific Region‐ past,
present and future. Diabetes Res. Clin. Pract. 103: 244–255.
3 Huang, Y.Y., Lin, K.D., Jiang, Y.D. et al. (2012). Diabetes‐related kidney, eye, and foot disease
in Taiwan: an analysis of the nationwide data for 2000‐2009. J. Formos. Med. Assoc. 111:
637–644.
4 Lazzarini, P.A., O’Rourke, S.R., Russell, A.W. et al. (2015). Reduced incidence of foot‐related
hospitalisation and amputation amongst persons with diabetes in Queensland, Australia.
PLoS One 10: e0130609.
  ­Reference 77

5 Kurowski, J.R., Nedkoff, L., Schoen, D.E. et al. (2015). Temporal trends in initial and
recurrent lower extremity amputations in people with and without diabetes in Western
Australia from 2000 to 2010. Diabetes Res. Clin. Pract. 108: 280–287.
6 Thewjitcharoen, Y., Krittiyawong, S., Porramatikul, S. et al. (2014). Outcomes of hospitalized
diabetic foot patients in a multi‐disciplinary team setting: Thailand’s experience. J. Clin.
Transl. Endocrinol. 1: 187–191.
7 Wang, C., Mai, L., Yang, C. et al. (2016). Reducing major lower extremity amputations after
the introduction of a multidisciplinary team in patient with diabetes foot ulcer. BMC Endocr.
Disord. 16: 38.
8 Fowkes, F.G., Rudan, D., Rudan, I. et al. (2013). Comparison of global estimates of
prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic
review and analysis. Lancet 382: 1329–1340.
9 Zhang, X., Ran, X., Xu, Z. et al. (2018). Epidemiological characteristics of lower extremity
arterial disease in Chinese diabetes patients at high risk: a prospective, multicenter, cross‐
sectional study. J. Diabetes. Complications. 32(2): 150–156.
 79

4g

The Diabetic Foot Worldwide: Middle East

Samir H. Assaad-Khalil
Department of Internal Medicine, Unit of Diabetology, Lipidology & Metabolism, Diabetes Foot Care Centre, Faculty of
Medicine, Alexandria University, Alexandria, Egypt

4g.1 ­The Burden of Diabetic Foot Disease (DFD)

in the Middle East (ME)

Unlike the situation in developed countries where data on the prevalence of amputation
can be obtained relatively easily and accurately, the situation in developing countries is less
clear due to lack of reliable registries [1]. In fact, there is a very low contribution of the
Arab world in research related to DFD. Out of 8612 publications globally, only 115 are
derived from our region [2]. Moreover, the prevalence results issued from the same country
may be controversial due to different methodology or to regional sampling rather than
nationwide screening.

Prevalence of diabetic foot disease in some ME countries

Non-Traumatic
Country Amputations Active Ulcerations Sensory Neuropathy PVS References

Egypt 4.4% 8.7% 29.3% 11% 3

SA 10% to 59% 12.5% 11.7% 4–7
Iraq 2.1%. 13.7%, 8
a
Kuwait 6.0% 9
Jordan 1.7 4.6% 14.9% 7.5% 10
UAE 0% 0ne out of 513 39% 12% 11
patients

SA = Saudi Arabia.
UAE = United Arab Emirates.
a
Computed amongst patients with DFD.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
80 4g The Diabetic Foot Worldwide: Middle East

In Egypt, in about 2000 patients with type 2 diabetes, 4.4% had a history of non‐­traumatic
amputation (6.2% in males; 2.6%, in females). DFD was associated with disease duration,
history of coronary artery disease, stroke, Peripheral Vascular Disease (PVD), laser photo-
coagulation, sensory neuropathy and renal replacement therapy [3]. In Saudi Arabia
(SA), a review analysis showed that 3970 amputations were performed in 2012 (incidence
rate of 2.6 per 10 000 people at risk) [1]; 92.7% of cases with PVD were asymptomatic [5].
The prevalence of fungal infection was 19.9% [6]. In Iraq, in a study of 182 subjects with
diabetes, diabetic foot abnormalities were reported in 46.7% of patients [8]. In Kuwait,
amongst recruited cases of DFD, the most common lesion was foot infection (43.5%)
­followed by ulcer (36.0%), gangrene (14.5%) and amputation (6.0%) [9]. In Jordan, ulcera-
tion was associated mainly with the male gender, neuropathy, and duration of diabetes
[10]. In the United Arab Emirates (UAE), trophic skin and nail abnormality were found
3% of patients [11].

4g.2 ­Specific Regional Barriers to Healthy Feet

and Foot Care

4g.2.1 Fatalism
The Arabs, whether Muslims or Christians, share many common cultural values and
beliefs such as fatalism. In Lebanon, a study observed that patients with diabetes are
more likely to endorse fatalistic attitudes to justify mal‐adherence [12]. Multiple
­l inear regression found an independent association between diabetes fatalism and
­c omorbidities [13].

4g.2.2 Complementary or Alternative Medicine (CAM)

In Egypt, in a sample of 1100 patients, 41.7% were CAM users. Whilst, white lupin grains
(Lupinus albus) comes as the most common type of CAM used by 43%, 29% of users
reported intake of unknown mixtures. Poor compliance to pharmacotherapy was more
reported amongst CAM users [14]. These products have never been subjected to evidence‐
based research; hence their potential danger. Rare exceptions have been subjected to RCT
such as the use of Resveratrol in foot ulcers [15].
In Saudi Arabia many patients still rely on CAM; 47.1% use conventional medicine
alone and 31.2% used both types of treatment. Honey is the most commonly used topical
product (56.6%) [16].

4g.2.3 Healers’ Popular Medicine

Cautery: In DFDs, it is applied on the dorsum of the foot or the lateral aspect of the lower
leg. Bloodletting is carried out at the ankle. Over‐the‐counter preparations removing
warts or corns are widely used. Topical henna paste besides its folk use is used for foot
and nail fungus, warts, etc.…; this may mask many local morbidities such as infections or
ischemia.
 4g.5 ­Foot Care, Education and Awarenes 81

4g.3 ­Misconceptions

The use of hot‐water bottles and hot foot baths for a prolonged period, a common prac-
tice in the region, predisposes to skin burns and infections. Men consider that the use of
moisturizing creams for their feet or asking the service of a chiropodist, are incompat-
ible with their manhood. Antidiabetic therapy, particularly insulin, is believed by many
people to trigger serious complications as amputation and blindness.

4g.3.1 Sedentary Life:

Due to weather, social and economic factors 46–70% of women and 35–58% of men are
physically inactive [17]. Besides, predisposing to CV diseases this can mask PVD; as most
of those suffering from advanced PVD do not complain of symptoms.

4g.3.2 Religious Practices

The frequent foot wash imposed by Islam Faith (5 ablutions per day) is beneficial as regards
cleanness of the feet; yet, predisposes to dryness. Besides, the wrong notion that drying the
feet may spoil the ablution (47% of people) invites fungal infection of the wet skin. Nail
trimming encouraged by faith may increase foot hygiene and self‐inspection; yet may
increase trauma.

4g.4 ­Footwear

Due to hot climate, and readiness for prayer, the common footwear is slippers or san-
dals. These have a ridge that fits between the first and the second toe, eliciting a high
mechanical pressure on the plantar surface of the foot leading to a callus and ultimately
a neuropathic foot ulcer. This is also predisposing the feet for injuries from hazardous
objects in the streets.

4g.5 ­Foot Care, Education and Awareness

Lack of education has proven to be a risk factor for the occurrence of ulceration in studies
from Egypt [18] Kuwait [9] and SA [19]. A cross‐sectional survey involving 1800 diabetic
patients followed by an educational intervention was carried out in Alexandria, Egypt.
More than three‐quarters of the studied patients reported that their feet have never been
inspected by their physicians and about 90% of them had never been examined for periph-
eral sensation or vascular status. A significant improvement in the foot care knowledge and
practices was observed after the educational intervention [18].
In SA, 77.1% examine their feet whilst 49.1% received foot care education. There is a sig-
nificant statistical association between foot education, foot care practices, and diabetic foot
ulcer [19]. Regarding attitudes towards foot wounds, 75.5% of males sought medical advice,
82 4g The Diabetic Foot Worldwide: Middle East

compared to 46.0% of females. Males were more adherent to foot drying (65.2%), whilst
females were applying more attention to skin softening (72.3%) [20].
In essence, in the ME, peculiarities in the environmental, cultural and socioeconomic
factors have a deleterious impact on foot health and care. Fortunately, these barriers are
reversible by education and structured care. The data on the burden of DFD are lacking.
Filling this gap besides translational and cost economic researches is mandatory for
national health programmes targeting foot health.

­References

1 Alzahrani, H.A. (2012). Diabetes‐related lower extremities amputations in Saudi Arabia:

the magnitude of the problem. Ann. Vasc. Dis. 5: 151–156.
2 Owiss, H., Alzahrani, H.A., Yousef, S. et al. (2013). The diabetic foot research in Arabs’
countries. Open J. Endocr. Metab. Dis. 3: 157–165.
3 Assaad‐Khalil, S.H., Zaki, A., Abdel Rehim, A. et al. (2015). Prevalence of diabetic foot
disorders and related risk factors among Egyptian subjects with diabetes. Prim. Care
Diabetes 9: 297–303.
4 Qidwai, S.A., Khan, M.A., Hussain, S.R. et al. (2001). Diabetic neuroarthropathy. Saudi.
Med. J. 22: 142–145.
5 Al‐Sheikh, S.O., Aljabri, B.A., Al‐Ansary, L.A. et al. (2007). Prevalence of and risk factors
for peripheral arterial disease in Saudi Arabia: a pilot cross‐sectional study. Saudi. Med. J.
28: 412–414.
6 Zimmo, S.K. (2007). Prevalence of dermatologic foot diseases in Saudi Arabia. J. Pan. Arab.
League. Dermatol. 18: 9–13.
7 Qari, F.A. and Akbar, D. (2000). Diabetic foot: presentation and treatment. Saudi. Med. J.
21: 443–446.
8 Mansour, A.A. and Imran, H.J. (2006). Foot abnormalities in diabetics: Prevalence &
predictors in Basrah, Iraq. Pak. J. Med. Sci. 22: 229–233.
9 Kholoud, A., Salma, G., and Nagafa, S. (2015). Diabetic foot risk factors including
knowledge, attitude and practice in Kuwaiti patients. Greener Journal of Medical Sciences
5: 058‐066. https://doi.org/10.15580/GJMS.2015.4.090715127.
10 Bakri, F.G., Allan, A.H., Khader, Y.S. et al. (2012). Prevalence of diabetic foot ulcer and its
associated risk factors among diabetic patients in Jordan. Jordan Med. J. 46: 118–125.
11 Maskari, F.A. and El‐Sadig, M. (2007). Prevalence of risk factors for diabetic foot
complications. BMC Fam. Pract. 8: 59.
12 Sukkarieh‐Haraty, O. and Howard, E. (2015). Is social support universally adaptive in
diabetes? A correlational study in an Arabic‐speaking population with type 2 diabetes.
Holist. Nurs. Pract. 29: 37–47.
13 Sukkarieh‐Haraty, O., Egede, L.E., Abi Kharma, J. et al. (2017). Predictors of diabetes
fatalism among Arabs: a cross‐sectional study of Lebanese adults with type 2 diabetes. J.
Relig. Health https://doi.org/10.1007/s10943‐017‐0430‐0.
14 Khalil, S.H., Zaki, A., Ibrahim, A.M. et al. (2013). Pattern of use of complementary and
alternative medicine among type 2 diabetes mellitus patients in Alexandria, Egypt. J. Egypt.
Public Health Assoc. 8: 137–142.
 ­Reference 83

15 Bashmakov, Y.K., Assaad‐Khalil, S.H., Abou Seif, M. et al. (2014). Resveratrol promotes
foot ulcer size reduction in type 2 diabetes patients. ISRN Endocrinol.: 816307. https://
doi.org/10.1155/2014/816307.
16 Thomas M, Hamdan M, Hailes S, Mic. (2010). Top ten natural preparations for the
treatment of diabetic foot disorders. Wounds UK; 6:18–26.
17 Al‐Nakeeb, Y., Lyons, M., Collins, P. et al. (2012). Obesity, physical activity and sedentary
behavior amongst British and Saudi youth: a cross‐cultural study. Int. J. Environ. Res. Public
Health 9: 1490–1506.
18 Assaad Khalil, S.H., Elamrawy Sh, M., Darwish, E.A.F. et al. (2010). Foot ulceration and
lower extremity amputations among diabetic patients in Alexandria, Egypt: prevalence,
predictors and quality of medical care. J. Egypt. Soc. Endocr, Diab. & Metab. 42: 125–130.
19 Goweda, R., Shatla, M., Alzaidi, A. et al. (2017). Assessment of knowledge and practices of
diabetic patients regarding diabetic foot care, in Makkah, Saudi Arabia. J. Family Med.
Health Care 3: 17–22.
20 Solana, Y.M., Kheira, H.M., Mahfouz, M.S. et al. (2016). Diabetic foot care: knowledge and
practice. J. Endocrinol. Metab. 6: 172–177.
 85

4h

The Diabetic Foot Worldwide: Australasia

Peter A. Lazzarini1,2
1
Allied Health Research Collaborative, The Prince Charles Hospital, Brisbane, Queensland, Australia
2
School of Clinical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia

4h.1 ­Introduction

Australasia is a global region of ~40 million people scattered across >20 island nations in
the southern Pacific Ocean [1]. Nations range from the larger, higher income, English‐
speaking nations of Australia (~24.5 million) and New Zealand (~4.5 million), to the many
smaller, lower income, mostly non‐English speaking nations of the Pacific Islands (~11
million) [1]. This section will discuss the diabetic foot disease burdens, care and research in
Australia, New Zealand, and the Pacific Islands.

4h.2 ­Australia

Over the past decade, Australia has improved its diabetes‐related amputation rate ranking
from the second worst to around tenth best, in comparison to >20 Organisation for
Economic Cooperation and Development (OECD) nations [2, 3]. Yet, diabetic foot disease
(ulcers, infection, or [critical] ischaemia) is still the leading cause of amputations, a leading
cause of hospitalisations and death, and costs ~$1.6 billion each year in Australia [2, 4, 5].
Furthermore, these diabetic foot disease outcomes are worse in indigenous, rural, and
poorer populations [2, 4, 6]. It is estimated that 50 000 (0.2%) Australian residents have
active diabetic foot ulcers at any one time with another ~300 000 (1.2%) at risk of develop‑
ing diabetic foot ulcers (with peripheral neuropathy or peripheral arterial disease) [4, 7].
This large burden of diabetic foot disease in Australia has been attributed to a national
lack of awareness, access to care and research [4, 6]. However, recent improvements in the
national burden have coincided with some Australian regions reporting <70% reductions
in hospitalization, amputation and cost rates after implementing coordinated evidence‐
based foot care and research [4, 8–10]. Further studies have also demonstrated that provid‑
ing evidence‐based foot care to populations from diverse indigenous, rural and income
backgrounds have produced equivalent improved diabetic foot outcomes [4, 5]. This

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
86 4h The Diabetic Foot Worldwide: Australasia

s­ uggests access to quality care is perhaps the largest determinant of the national diabetic
foot disease burden in Australia [4, 5].
In 2016, on the back of these promising findings, Australia established a national goal of
‘ending avoidable amputations in a generation’ and a national diabetic foot body: Diabetic
Foot Australia (DFA) [4]. DFA has since produced national guidelines, minimum datasets,
conferences, education, and has campaigned for increased investments in diabetic foot dis‑
ease [4]. Most recently, DFA led the launch of an Australian diabetes‐related foot disease
strategy 2018–2022 aimed at ensuring people with diabetic foot disease, have: (i) access to
care, (ii) safe quality care, and (iii) high‐quality research that strives to improve care [4].
Over the next decade, Australia has stated its desire to become a world‑leading nation
when it comes to diabetic foot disease burden, care and research [4].

4h.3 ­New Zealand

New Zealand has consistently ranked within the top‐10 OECD nations for national
­diabetes‐related amputation rates [3, 11]. Yet, like Australia, diabetic foot disease is still the
leading cause of amputation and a leading cause of death in New Zealand [11, 12]. Again,
like Australia, these outcomes are worse in indigenous Maori and poorer populations [11,
12]; but not in rural populations, perhaps because of New Zealand’s smaller geographical
area [11, 12]. It is estimated that 14 000 (0.3%) New Zealand residents have active diabetic
foot ulcers with another ~75 000 (1.6%) at risk of developing diabetic foot ulcers [7, 13].
New Zealand’s more modest burden of diabetic foot disease has been attributed to an
integrated national health care system and a focus on high‐quality research into diabetic
foot disease [3, 11, 12]. New Zealand authors recently published some of the first studies to
monitor an entire nation’s diabetes population to determine predictors of amputations [11,
12]. These huge studies identified that whilst being indigenous Maori was a predictor of
amputation, being a Pacific Islander was not [11, 12]. With Maori and Pacific Islanders hav‑
ing similar Polynesian genetics this indicates other non‐genetic factors are more important
risk factors for amputation [11, 12]. Furthermore, they identified that increasing co‐mor‑
bidities predicted amputation; suggesting that the sicker the patient, the more likely they
will need an amputation [11, 12]. For a small OECD nation, New Zealand is arguably already
a world‑leading nation when it comes to diabetic foot disease burden, care and research.

4h.4 ­Pacific Islands

Pacific Island nations have historically recorded some of the highest diabetes‐related ampu‑
tation rates in the world [14], and have much higher diabetic foot ulcer prevalence than
Australia and New Zealand (Figure 4h.1) [7]. The prevalence of active diabetic foot ulcers
in national resident populations range from 0.35% (~27 000 people in Papua New Guinea)
to 1.0% (~9000 in Fiji) [7]. These high rates have been attributed to ethnicity, lower incomes,
and poorer access to health care in these nations [14].
Diabetic foot disease research has also been limited in the Pacific Islands [14]. However,
recent studies have for the first time reported national diabetic foot prevalence across
  ­Reference 87

1200

1000
per 100,000 residents

800

600

400

200

0
ji
Fi

u
s

oa

ia

oa

te
a

lia
a
i

d
at
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es
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Figure 4h.1 National prevalence of diabetic foot ulceration in Australasia [7].

Pacific Islands [7, 15]. Interestingly, whilst the prevalence of risk factors for foot disease in
people with diabetes in the Pacific Islands (~18–30%) were similar to Australia and New
Zealand (~24–32%) [15]; these studies also found the prevalence of active foot ulcers (~5–
8%) was much higher (~3–4%) [15]. These higher rates have been attributed to poor meta‑
bolic control, poor access to care, and increased use of traditional remedies [15]. This has
seen the Pacific Islands recording some of the highest diabetic foot disease burdens per
population in the world [7, 15].

4h.5 ­Conclusion

Large disparities exist in Australasia in terms of diabetic foot burdens, care and research
which are seemingly driven by equally large disparities in income, ethnicity and rurality.
Yet, recent Australasian research has demonstrated that improved access to evidence‐based
care reduces diabetic foot disease burdens and nullifies any historical income, ethnicity
and rurality drivers. With this, and other world‑leading research and care in mind, perhaps
it is beholden on New Zealand and Australia to help coordinate improved diabetic foot care
and research for all Australasian nations. With such coordinated improved care and
research across Australasia, existing diabetic foot disease disparities should diminish, and
Australasia may just become a world‑leading global region for diabetic foot disease burden,
care, and research outcomes in the foreseeable future.

R
­ eferences

1 United Nations (2017). World Population Prospects (2017). New York: United Nations.
https://esa.un.org/unpd/wpp/DataQuery (accessed on March 5 2018).
2 Lazzarini, P.A., Gurr, J.M., Rogers, J.R. et al. (2012). Diabetes foot disease: the Cinderella of
Australian diabetes management? J. Foot Ankle. Res. 5: 24–24.
88 4h The Diabetic Foot Worldwide: Australasia

3 Carinci, F., Massi Benedetti, M., Klazinga, N.S., and Uccioli, L. (2016). Lower extremity
amputation rates in people with diabetes as an indicator of health systems performance. A
critical appraisal of the data collection 2000–2011 by the Organization for Economic
Cooperation and Development (OECD). Acta Diabetol. 53: 825–832.
4 Van Netten, J.J., Lazzarini, P.A., Fitridge, R. et al. (2017) Australian diabetes‐related foot
disease strategy 2018–2022: The first step towards ending avoidable amputations within a
generation. Brisbane: Wound Management CRC;. https://www.diabeticfootaustralia.org/
for‐researchers/australian‐diabetes‐related‐foot‐disease‐strategy‐2018‐2022 (accessed on
March 5 2018).
5 Lazzarini, P.A. (2016) The burden of foot disease in inpatient populations [PhD by
publication]. Brisbane, Australia: School of Clinical Sciences, Queensland University of
Technology;. https://eprints.qut.edu.au/101526 (accessed on March 5 2018).
6 Bergin, S.M., Alford, J.B., Allard, B.P. et al. (2012). A limb lost every 3 hours: can Australia
reduce amputations in people with diabetes? Med. J. Aust. 197: 197–198.
7 Institute for Health Metrics and Evaluation (IHME) (2017). Epi Visualization: Global
Burden Disease 2015 data. Seattle, WA: IHME, University of Washington. https://vizhub.
healthdata.org/epi (accessed on March 5 2018).
8 Kurowski, J.R., Nedkoff, L., Schoen, D.E. et al. (2015). Temporal trends in initial and
recurrent lower extremity amputations in people with and without diabetes in Western
Australia from 2000 to 2010. Diabetes Res. Clin. Pract. 108: 280–287.
9 Lazzarini, P.A., O’Rourke, S.R., Russell, A.W. et al. (2015). Reduced incidence of foot‐
related hospitalisation and amputation amongst persons with diabetes in Queensland,
Australia. PLoS One 10: e0130609.
10 Cheng, Q., Lazzarini, P.A., Gibb, M. et al. (2017). A cost‐effectiveness analysis of optimal
care for diabetic foot ulcers in Australia. Int. Wound J. 14: 616–628.
11 Gurney, J.K., Stanley, J., York, S. et al. (2018). Risk of lower limb amputation in a national
prevalent cohort of patients with diabetes. Diabetologia 61: 626–635.
12 Robinson, T.E., Kenealy, T., Garrett, M. et al. (2016). Ethnicity and risk of lower limb
amputation in people with Type 2 diabetes: a prospective cohort study. Diabet. Med. 33:
55–61.
13 O’Shea, C., McClintock, J., and Lawrenson, R. (2017). The prevalence of diabetic foot
disease in the Waikato region. Diabetes Res. Clin. Pract. 129: 79–85.
14 Humphrey, A.R., Dowse, G.K., Thoma, K., and Zimmet, P.Z. (1996). Diabetes and
nontraumatic lower extremity amputations. Incidence, risk factors, and prevention – a 12‐
year follow‐up study in Nauru. Diabetes Care 19: 710–714.
15 Win Tin, S.T., Kenilorea, G., Gadabu, E. et al. (2014). The prevalence of diabetes
complications and associated risk factors in Pacific Islands countries. Diabetes Res. Clin.
Pract. 103: 114–118.
 89

Diabetic Neuropathy
Dinesh Selvarajah, Gordon Sloan, and Solomon Tesfaye
University of Sheffield, Sheffield, UK

5.1 ­Epidemiology

Polyneuropathy is one of the commonest complications of the diabetes [1] and is a major
cause for non‐traumatic lower limb amputations in the developed World [1]. Diabetic poly-
neuropathy encompasses several neuropathic syndromes the commonest of which is distal
sensorimotor symmetrical neuropathy, the main initiating factor for foot ulceration [1]. It
leads to disabling unsteadiness [2] and distressing neuropathic pain which is often
­unresponsive to therapy [3]. The epidemiology of diabetic neuropathy has recently been
reviewed [4]. It is very common, with a life‐time prevalence of 50% for people with diabetes
[1]. Unfortunately, the early manifestations of this insidious disease are often missed until
the disease is well established, at which point it appears irreversible. Notwithstanding the
costs to the individual, diabetic neuropathy is associated with a significant health care bur-
den; in the USA the total annual cost of diabetic neuropathy and its complications was
estimated to be between $4.6 and $13.7 billion, with up to 27% of the direct medical cost of
diabetes attributed to DPN [5]. The EURODIAB Prospective Complications Study which
involved the examination of type 1 patients, from 16 European countries, found a preva-
lence rate of 28% for distal symmetrical neuropathy [6]. Based on this and other recent
epidemiological studies, risk factors for diabetic neuropathy include increasing age,
increasing duration of diabetes, poor glycaemic control, retinopathy, albuminuria, and
­vascular risk factors [7]. The differing clinical presentation of the several neuropathic
­syndromes in diabetes suggests varied etiological factors.

5.2 ­Classification

Diabetic neuropathy is a heterogeneous group of conditions and clinical classification of the

various syndromes has proved challenging. The variation and overlap in aetiology, ­clinical
presentation, natural history, and prognosis has meant that most classifications are ­necessarily

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
90 5 Diabetic Neuropathy

over‐simplified, and none has proved capable of accounting for all these factors. Clinical
manifestations and measurement of somatic neuropathy have recently been the subject of a
technical review with in‐depth discussion and relevant references to the literature [1].
Table 5.1 provides a comprehensive classification scheme for diabetic neuropathies recently
recommended in a Position Statement by the American Diabetes Association [8].

Table 5.1 Classification for diabetic neuropathies [8].

Classification for diabetic neuropathies

Diabetic neuropathies
A) Diffuse neuropathy
Distal Symmetrical Peripheral Neuropathy
●● Primarily small‐fibre neuropathy

●● Primarily large‐fibre neuropathy

●● Mixed small‐ and large‐fibre neuropathy (most common)

Autonomic
Cardiovascular
●● Reduced Heart Rate Variability

●● Resting tachycardia

●● Orthostatic hypotension

●● Sudden death (malignant arrhythmia)

Gastrointestinal
●● Diabetic gastroparesis (gastropathy)

●● Diabetic enteropathy (diarrhoea)

●● Colonic hypomotility (constipation)

Urogenital
●● Diabetic cystopathy (neurogenic bladder)

●● Erectile dysfunction

●● Female sexual dysfunction

Sudomotor dysfunction
●● Distal hypohydrosis/anhidrosis,

●● Gustatory sweating

Hypoglycemia unawareness
Abnormal pupillary function
B) Mononeuropathy (mononeuritis multiplex) (atypical forms)
Isolated cranial or peripheral nerve (e.g., Cranial Nerve III, ulnar, median, femoral, peroneal)
Mononeuritis multiplex (if confluent may resemble polyneuropathy)
C) Radiculopathy or polyradiculopathy (atypical forms)
Radiculoplexus neuropathy (a.k.a. lumbosacral polyradiculopathy, proximal motor
amyotrophy)
Thoracic radiculopathy
Nondiabetic neuropathies common in diabetes
Pressure palsies
Chronic inflammatory demyelinating polyneuropathy
Radiculoplexus neuropathy
Acute painful small‐fibre neuropathies (treatment‐induced)
 5.3 ­Symmetrical Neuropathie 91

5.3 ­Symmetrical Neuropathies

5.3.1 Distal Symmetrical Polyneuropathy

This is the commonest neuropathic syndrome and what is meant in clinical practice by the
phrase ‘diabetic neuropathy’. There is a ‘length‐related’ pattern of sensory loss, with sensory
symptoms starting in the toes and then extending to involve the feet and legs in a stocking
distribution. In more severe cases, there is often upper limb involvement, with a similar
progression proximally starting in the fingers. Although the nerve damage can extend over
the entire body including the head and face, this is exceptional. Patients with pre‐diabetes
may also develop neuropathies that are similar to diabetic neuropathies [9]. As the disease
advances, overt motor manifestations such as wasting of the small muscles of the hands and
limb weakness may become apparent. However, sub‐clinical motor involvement detected
by magnetic resonance imaging appears to be common, and thus motor disturbance is
clearly part of the functional impairment caused by distal symmetrical neuropathy [10].
The main clinical presentation of distal symmetrical neuropathy varies according to the
class of sensory fibres involved. Sensory loss which the patient may be asymptomatic, or
may be described as ‘numbness’ or ‘dead feeling’ is attributed to large fibre involvement.
However, some may experience a progressive build‐up of unpleasant sensory symptoms
including tingling (paraesthesiae); burning pain; shooting pains down the legs; lancinating
pains; contact pain often with day‐time clothes and bedclothes (allodynia); pain on walking
often described as ‘walking barefoot on marbles’, or ‘walking barefoot on hot sand’;
­sensations of heat or cold in the feet; persistent achy feeling in the feet and cramp‐like
­sensations in the legs. Occasionally, pain can extend above the feet and may involve the
whole of the legs, and when this is the case there is usually upper limb involvement also.
There is a large spectrum of severity of these symptoms which reflect different degrees of
small fibre involvement. Some may have minor complaints such as tingling in one or two
toes; others may be affected with the devastating complications such as ‘the numb diabetic
foot’, or severe painful neuropathy that does not respond to drug therapy. Neuropathic pain
is ­present in 25% of patients with diabetes and can be the first symptom that prompts
patients to seek medical attention [11].
Diabetic neuropathic pain is characteristically more severe at night, and often prevents
sleep. Some patients may be in a constant state of tiredness because of sleep deprivation.
Others are unable to maintain full employment. Severe painful neuropathy can occasion-
ally cause marked reduction in exercise threshold so as to interfere with daily activities. Not
surprisingly therefore, significant emotional distress is common [12].
It is important to appreciate that many subjects with distal symmetrical neuropathy may
not have any of the above symptoms, and their first presentation may be with a foot ulcer.
This underpins the need for carefully examining and screening the feet of all people with
diabetes, in order to identify those at risk of developing foot ulceration. The insensate neu-
ropathic foot is at risk of developing mechanical and thermal injuries, and patients must
therefore be warned about these and given appropriate advice regarding foot care. Foot
ulceration and Charcot neuroarthropathy are late complications of diabetic neuropathy. In
addition, in those with advanced neuropathy, there may be sensory ataxia secondary to loss
of proprioception. The unfortunate sufferer is affected by unsteadiness on walking, and
92 5 Diabetic Neuropathy

even falls and fractures particularly if there is associated visual impairment due to retin-
opathy. Patients often report that unsteadiness is the most disabling symptom experienced
and it is the main contributor to depression and social isolation [13].
Neuropathy is usually easily detected by careful history and simple bedside clinical
examination. Detailed neurophysiological assessments or referral to neurologists is sel-
dom necessary. Shoes and socks should be removed, and the feet examined at least
annually and more often if neuropathy is present. As the disease progresses there is sym-
metrical sensory loss which begins distally (toes) in a ‘stocking’ and sometimes in a
‘glove’ distribution involving all sensory modalities. Assessments of large fibre function
includes: Vibration perception using a 128‐Hz tuning fork. Light touch perception using
either cotton wool or a 10 g monofilament. The latter is a validated tool which detects
more advanced neuropathy and often used to identify patients with an increased risk of
ulceration and amputation [14]. Other assessments of large fibre function include pro-
prioception and ankle reflexes. When there is advanced neuropathy, proprioception may
also be impaired, leading to a positive Romberg’s sign and ankle tendon reflexes are lost.
Knee reflexes are often reduced or absent. Small fibre function can be assessed using a
pin‐prick and thermal test.
Muscle strength is usually normal early during the course of the disease, although mild
weakness may be found in toe extensors. However, with progressive disease there is signifi-
cant generalized muscular wasting, particularly in the small muscles of the hand and feet.
The fine movements of fingers would then be affected, and there is difficulty in handling
small objects. Wasting of dorsal interossei is however usually due to entrapment of the ulnar
nerve at the elbow. The clawing of the toes is believed to be due to unopposed (because of
wasting of the small muscles of the foot) pulling of the long extensor and flexor tendons.
This scenario results in elevated plantar pressure points at the metatarsal heads that are
prone to callus formation and foot ulceration. Deformities such as a hallux valgus, often
referred to as a bunion, can form the focus of ulceration and with more extreme deformities,
such as those associated with Charcot arthropathy, the risk is further increased. As one of the
most common precipitants to foot ulceration is inappropriate footwear, a thorough assess-
ment should also include examination of shoes for poor fit, abnormal wear, and internal
pressure areas or foreign bodies.
In recent years, significant progress has been made to develop non‐invasive point‐of‐care
testing devices that are capable of diagnosing early, subclinical neuropathy. A recent review
by Papanas et al. discusses these devices in depth [15]. A key feature of these devices is that
they are quick and simple to perform by any healthcare professional, only requiring
­minimal training and can feasibly be incorporated into a busy clinic setting. Overall, the
sensitivity of these devices, also appear acceptable and perhaps a combination of devices
may be used in the future for detecting diabetic neuropathy
Current guidance recommends screening for diabetic neuropathy is performed annually
from diagnosis of type 2 diabetes (T2DM) and five years after diagnosis of type 1 diabetes
(T1DM) [8]. In addition, all patients should have an annual 10 g monofilament testing to
assess for loss of protective sensation in order to identify individuals at risk of ulceration and
amputation. The loss of the ‘gift of pain’, together with foot deformities and limited joint
mobility, combine to create regions of elevated plantar pressures which leads to foot ulcera-
tion. Patients should be informed of their risk of foot ulcerations (Table 5.2). Those at
 5.3 ­Symmetrical Neuropathie 93

Table 5.2 Diabetic foot risk assessment.

Definition Action

Low Normal sensation, palpable pulses Standard footcare advice and

Moderate One risk factor present e.g.
neuropathy or absent foot pulses or
foot deformity or skin changes
High Previous ulcer or amputation or
more than one risk factor e.g.
neuropathy or absent pulses plus
deformity or skin changes
Foot ulceration Presence of active ulceration/break
in the skin, spreading infection,
gangrene or unexplained hot, red,
swollen foot with or without pain
information leaflets
●● Surveillance 3–6 monthly by
healthcare professional with
footcare competencies training
●● Enhanced foot care education
●● Inspect feet 3–6 monthly
●● Advise on appropriate footwear
●● Review need for vascular assessment
●● Increased surveillance 1–3 monthly
by specialist podiatrist or member of
the foot protection team
●● At each regular Diabetes visit review
education / footwear / vascular status
●● Rapid referral to multidisciplinary
foot care team
●● Admission to secondary care if
patient systemically unwell

increased or high risk should be provided with education on preventative foot self‐care, guid-
ance on appropriate footwear, orthotic input and/or regular podiatric foot management.

5.3.1.1 Differential Diagnosis of Distal Symmetrical Neuropathy

Diabetic peripheral neuropathy presents in a similar way to neuropathies of other causes,
and thus the physician needs to carefully exclude these before attributing the neuropathy
to diabetes. Absence of other complications of diabetes, rapid weight loss, excessive alcohol
intake, and other atypical features in either the history or clinical examination should alert
the physician to search for other causes of neuropathy. Table 5.3 shows differential diagno-
ses for distal symmetrical neuropathy.

5.3.1.2 Natural History of Distal Symmetrical Neuropathy

Although distal symmetrical neuropathy is common in clinical practise, there are few
­prospective studies that have looked at its natural history, therefore it remains poorly
understood. This may partly be due to our inadequate knowledge regarding the pathogen-
esis of distal symmetrical neuropathy, although several mechanisms have been suggested
[16]. Unlike in diabetic retinopathy and nephropathy, the lack of a simple, accurate and
readily reproducible method of measuring neuropathy further complicates the problem.
Furthermore, the methods that we currently use (e.g. standardized clinical assessments,
10 g monofilament and tuning fork) are not only subjective and reliant on the examiner’s
interpretations but tend to diagnose neuropathy when it is already well established.
Many of these patients end up with foot ulceration which drives amputation risk and eco-
nomic costs and are also predictors of mortality [17].
94 5 Diabetic Neuropathy

Table 5.3 Differential diagnosis of distal symmetrical neuropathy.

Metabolic
Diabetes
Amyloidosis
Uraemia
Myxoedema
Porphyria
Vitamin deficiency (thiamine, B12, B6, pyridoxine)
Drugs and chemicals
Alcohol
Cytotoxic drugs, e.g. Vincristine
Chlorambucil
Nitrofurantoin
Isoniazid
Neoplastic disorders
Bronchial or gastric carcinoma
Lymphoma
Infective or inflammatory
Leprosy
Guillain‐Barre syndrome
Lyme borreliosis
Chronic inflammatory demyelinating polyneuropathy
Polyarteritis nodosa
Genetic
Charcot–Marie–Tooth disease
Hereditary sensory neuropathies

5.3.2 Acute Painful Neuropathies

These are transient neuropathic syndromes characterized by an acute onset of pain in the
lower limbs. Acute neuropathies present in a symmetrical fashion and are relatively
uncommon. Pain is invariably present and is usually distressing to the patient, and this can
sometimes be incapacitating. There are two distinct syndromes, the first of which occurs
within the context of poor glycaemic control, and the second with rapid improvements in
metabolic control.

5.3.2.1 Acute Painful Neuropathy of Poor Glycaemic Control

This phenomenon occurs usually in T1DM or T2DM diabetic subjects with poor glycaemic
control. There is no relationship to the presence of other chronic diabetic complications.
There is often an associated severe weight loss often described as ‘neuropathic cachexia’
[4]. Patients typically develop persistent burning pain associated with allodynia (contact
 5.4 ­Asymmetrical Neuropathie 95

pain). The pain is most marked in the feet but often affects the whole of the lower extremi-
ties. As in chronic distal symmetrical neuropathy, the pain is typically worse at night
although persistent pain during daytime is also common. The pain is likened to ‘walking on
burning sand’ and there may be a subjective feeling of the feet being ‘swollen’. Patients also
describe intermittent bouts of stabbing pain that shoot up the legs from the feet (‘peak
pain’), superimposed on the background of burning pain (‘background pain’).
On examination, sensory loss is usually surprisingly mild or even absent. There are usu-
ally no motor signs, although ankle jerks may be absent. Nerve conduction studies are also
usually normal or mildly abnormal and there is often a preponderance of small fibre dys-
function [4]. There is complete resolution of symptoms within 12 months, and weight gain
is usual with continued improvement in glycaemic control with the use of insulin.

5.3.2.2 Acute Painful Neuropathy of Rapid Glycaemic Control (Nee. Insulin Neuritis)
This form of acute painful neuropathy follows rapid improvement in glycaemic control. It
has a good prognosis with almost guaranteed improvement in contrast to chronic painful
distal symmetrical neuropathy. The patient presents with burning pain, paraesthesiae, allo-
dynia, often with a nocturnal exacerbation of symptoms; and depression may be a feature.
There is no associated weight loss, unlike acute painful neuropathy of poor glycaemic con-
trol. Sensory loss is often mild or absent, and there are no motor signs. There is little or no
abnormality on nerve conduction studies and complete resolution of symptoms usually
occur within 12 months. Rapid glycaemic changes in patients with uncontrolled diabetes
increased the risk of this complication and should be avoided. A 2–3% decreased in Hba1c
over three months is associated with a 20% absolute risk of developing this complication.
The risk exceeds 80% with a decreased in HbA1c of >4% [18].

5.4 ­Asymmetrical Neuropathies

Asymmetrical or focal neuropathies are well recognized complications of diabetes. They

have a relatively rapid onset, and complete recovery is usual. Unlike chronic distal sym-
metrical neuropathy, they are often unrelated to the presence of other diabetic complica-
tions. Asymmetrical neuropathies are more common in men and tend to predominantly
affect older patients.

5.4.1 Proximal Motor Neuropathy (Femoral Neuropathy, Amyotrophy,

Plexopathy)
The syndrome of progressive asymmetrical proximal leg weakness and atrophy was first
known as ‘diabetic amyotrophy’. This condition has also been named as ‘proximal motor
neuropathy’, ‘femoral neuropathy’ or ‘plexopathy’. The patient presents with severe
pain, which is felt deep in the thigh, but can sometimes be of burning quality and extend
below the knee. The pain is usually continuous and often causes insomnia and depres-
sion. It usually occurs in T2DM patients over the age of 60 with a one and half times
male preponderance [4]. There is an associated weight loss which can sometimes be
very severe.
96 5 Diabetic Neuropathy

On examination there is profound weakness and wasting of the quadriceps, although hip
flexors and hip abductors can also be affected. Thigh adductors, glutei, and hamstring mus-
cles may also be involved. The knee jerk is usually reduced or absent. The profound weak-
ness can lead to difficulty from getting out of a low chair or climbing stairs. Sensory loss is
unusual, and if present indicates a coexistent distal sensory neuropathy.
It is important to carefully exclude other causes of quadriceps wasting such as nerve root
and cauda equina lesions, and the possibility of occult malignancy causing proximal myo-
pathy syndromes. MR imaging of the lumbo‐sacral spine is now mandatory in order to
exclude focal nerve root entrapment and other pathologies. Electrophysiological studies
may demonstrate increased femoral nerve latency and active denervation/re‐innervation
of affected muscles.
The cause of diabetic proximal motor neuropathy is not known. It tends to occur within
the background of diabetic distal symmetrical neuropathy. As in distal symmetrical neu-
ropathy there is scarcity of prospective studies that have looked at the natural history of
proximal motor neuropathy. There may be residual distal weakness in half the patients.
Recurrence on the other side is common but relapse can occur in 10% of patients.
Management is largely symptomatic and supportive. Patients should be reassured that this
condition is likely to resolve. Some patients benefit from physiotherapy that involves exten-
sion exercises aimed at strengthening the quadriceps. The management of pain in proximal
motor neuropathy is similar to that of chronic or acute distal symmetrical neuropathies
(see below).

5.4.2 Focal Peripheral Neuropathies

A number of focal peripheral neuropathies involving cranial, thoracic or extremity nerves
are associated with diabetes. The commonest cranial neuropathy is the third cranial nerve
palsy. The patient presents with acute onset unilateral pain in the orbit, or sometimes with
a frontal headache. There is typically ptosis and ophthalmoplegia, although the pupillary
response to light is usually spared. Recovery occurs usually over three months. The clinical
onset and timescale for recovery, and the focal nature of the lesions on the third cranial
nerve, on post‐mortem studies suggested an ischaemic aetiology. It is important to exclude
any other cause of third cranial nerve palsy (aneurysm or tumour) by CT or MR scanning,
where the diagnosis is in doubt. Fourth, sixth and seventh cranial nerve palsies have also
been described in diabetic subjects, but the association with diabetes is not as strong as that
with third cranial nerve palsy.
Truncal radiculopathy is well recognized to occur in diabetes. It is characterized by an
acute onset pain in a dermatomal distribution over the thorax or the abdomen. The pain
is usually asymmetrical, and it can cause local bulging of the muscle. There may be
patchy sensory loss and other causes of nerve root compression should be excluded using
MR imaging. Some patients presenting with abdominal pain have undergone unneces-
sary investigations such as barium enema, colonoscopy and even laparotomy, when the
diagnosis could easily have been made by careful clinical history and examination.
Recovery is usually the rule within several months, although symptoms can sometimes
persist for a few years.
 5.5 ­Pathogenesis of Distal Symmetrical Neuropath 97

5.4.3 Pressure Palsies

A number of nerves including the median, ulnar, radial, lateral femoral cutaneous, fibular
and plantar nerves are vulnerable to pressure damage in diabetes. The aetiology is multifac-
torial involving metabolic and ischaemic factors, impaired reinnervation, and even obesity
[4]. Robust agreement between clinical and electrophysiological findings should guide
treatment decisions. In median nerve palsy, the patient typically has pain and paraesthesia
in the affected hand, which sometimes radiate to the forearm and are particularly marked
at night. In severe cases clinical examination may reveal a reduction in sensation in the
median territory in the hands, and a wasting of the muscle bulk in the thenar eminence.
The treatment involves surgical decompression at the carpel tunnel in the wrist. There is
generally good response to surgery in patients with diabetes (but not necessarily diabetic
neuropathy) who are thought to have the same beneficial outcome after carpal tunnel
release as non‐diabetic patients [19], although, painful symptoms appear to relapse more
commonly than in the non‐diabetic population.

5.4.3.1 Ulnar Nerve and Other Isolated Nerve Entrapments

The ulnar nerve is also vulnerable to pressure damage at the elbow in the ulnar groove.
This results in wasting of the dorsal interossei, particularly the first dorsal interossius. This
is easily confirmed by ulnar electrophysiological studies which localize the lesion to the
elbow. Rarely, the patients may present with wrist drop due to radial nerve palsy after pro-
longed sitting (with pressure over the radial nerve in the back of the arms) whilst uncon-
scious during hypoglycaemia or asleep after an alcohol binge.
In the lower limbs, the common peroneal (lateral popliteal) is the most commonly
affected nerve. The compression is at the level of the head of the fibula and causes foot
drop. Unfortunately, complete recovery is not usual. The lateral cutaneous nerve of the
thigh is occasionally also affected with entrapment neuropathy in diabetes.

5.5 ­Pathogenesis of Distal Symmetrical Neuropathy

Despite considerable research, the pathogenesis of diabetic neuropathy remains undeter-

mined [16]. This is one reason why, despite several clinical trials, there has been relatively
little progress in the development of disease‐modifying treatments [20]. Historically, there
have been two distinct views (based on either a metabolic or vascular hypothesis) with regard
to the pathogenesis of diabetic neuropathy (Table 5.4). However, most authorities now agree
that the truth is both metabolic and vascular factors are important. A more thorough review
of the pathogenesis of diabetic neuropathy can be found elsewhere [16].

5.5.1 Central Nervous System Involvement in Diabetic Neuropathy

There is mounting evidence of central nervous system (CNS) involvement in diabetic neuropa-
thy challenging the tradition view that it is a disease of the peripheral nervous system [21].
Recent magnetic resonance neuroimaging studies provide valuable insights into the CNS
98 5 Diabetic Neuropathy

Table 5.4 Proposed hypotheses of diabetic peripheral nerve damage.

Chronic hyperglycaemia
Nerve microvascular dysfunction
Increased free radical formation
Polyol pathway hyperactivity
Protein kinase C hyperactivity
Non‐enzymatic glycation
Abnormalities of nerve growth

a­ lterations [21]. From the spinal cord to the cerebral cortex, structural, functional, and meta-
bolic changes have been described. Although the initial injury may occur in the peripheral
nerve, concomitant changes within the CNS may have a crucial role in the pathogenesis and
determining the clinical phenotype of neuropathy.

5.6 ­Management of Diabetic Neuropathy

5.6.1 Prevention of Diabetic Neuropathy

There is now little doubt that chronic hyperglycaemia is implicated in the pathogenesis
of diabetic neuropathy [22]. In T1DM, it is clear, that the benefit of intensive glucose
control is greatest in younger patients at early stages of the disease [22]. This effect
becomes weaker once nerve damage is established. Conversely, in T2DM improving
­glycaemic control alone does not have the same impact [22]. Hence, it is likely that other
factors such as obesity, dyslipidaemia particularly hypertriglyceridaemia, hypertension,
smoking and obesity may be responsible [6]. There have only been a small number of
intervention studies targeting multiple risk factors which have used appropriate diabetic
neuropathy endpoints [22]. This includes several studies of intensive lifestyle interven-
tion in patients with T2DM [23]. These studies provide preliminary evidence for the
efficacy of multifactorial risk factor management in preventing the development and
progression of neuropathy.

5.6.2 Symptomatic Treatment of Painful Diabetic Neuropathy

The treatment scenario for painful neuropathy is less than satisfactory as currently
available treatment approaches are highly symptomatic and often ineffective [24]. The
quality and severity of pain should be carefully assessed. Neuropathic pain can be
­disabling, and an empathetic multidisciplinary approach is essential. This includes psy-
chological support which is an important aspect of the overall management especially
in patients with severe intractable pain. The aim of treatment is pursuing maximum
pain relief in order to restore or improve functional measures, quality of life, sleep, and
mood; at the same time remaining mindful of the limitations of pharmacotherapy
(including side‐effect profile and consequences of polypharmacy) and comorbidities.
 5.6 ­Management of Diabetic Neuropath 99

An initial realistic target would be to achieve a 50% reduction in pain intensity based on
a visual analogue scale or Likert scale.

5.6.2.1 Glycaemic Control

The risk factors for painful diabetic neuropathy are less well known. Weight, obesity, waist
circumference, peripheral arterial disease, and triglycerides have all been associated with
painful diabetic neuropathy in epidemiological studies [25]. Painful neuropathic symptoms
are reduced by improving metabolic control and reducing glycaemic variability, if necessary,
with the use of insulin in type 2 diabetes. Hence, the first step in the management of painful
neuropathy is a concerted effort aimed at improving glycaemic control.
Several pharmacotherapies have proven efficacy in painful diabetic neuropathy although
only pregabalin and duloxetine have been approved by the Food and Drugs Administration
of the U.S. and the European Medicines Agency for this indication.

5.6.2.2 Tricyclic Compounds

A number of double‐blind clinical trials have confirmed the effectiveness of tricyclic
­antidepressants in painful diabetic neuropathy. However, their use is limited by unwanted
side effects such as drowsiness and anticholinergic side effects such as dry mouth, dizzi-
ness, and postural hypotension (with the risk of falls particularly in the elderly). For this
reason, patients should be started on a low dose of imipramine or amitriptyline at night
(10 mg taken before bed), the dose gradually titrated if necessary up to 75 mg per day up to
150 mg/day on occasions. Higher doses have been associated with an increased risk of sud-
den ­cardiac death, and caution is advised in the elderly or in any patient with a history of
cardiovascular disease [26].

5.6.2.3 Anticonvulsants
Anticonvulsants, including carbamazepine, phenytoin, gabapentin, and pregabalin have
also been found effective in the relief of more severe neuropathic pain. Gabapentin and
pregabalin are agonist of the α2δ subunit of the calcium channel thereby reducing neuro-
transmitter release in the hyperexcited neuron. There have been several clinical trials of
pregabalin in painful diabetic neuropathy [27]. Unlike gabapentin, pregabalin has linear
pharmacokinetics and does not require a long titration period. Patients are usually started
on 75 mg twice a day for about a week and increased to 150 mg twice a day maintenance
dose with a maximum dose of 600 mg/day. Side effects of treatment with anticonvulsants
include sedation, dizziness, and ataxia Therefore treatment should be started at a relatively
low dose and gradually increased to maintenance dose of these drugs, whilst carefully
looking for side effects.

5.6.2.4 Selective Serotonin and Norepinephrine Reuptake Inhibitors

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitors (SNRI) which
relieves pain by increasing the synaptic availability of 5‐hydroxytryptamine and noradrena-
line in the descending inhibitory pain pathways. It also has the added advantage of being
an anti‐depressant. The efficacy of this agent has been confirmed in several clinical trials
100 5 Diabetic Neuropathy

in painful diabetic neuropathy at doses of 60 to 120 mg per day [28]. The most frequent side
effects include nausea, dizziness, somnolence, dry mouth, and reduced appetite, although
these tend to be mild and transient. Venlafaxine is another SNRI effective in neuropathic
pain relief but adverse cardiovascular events limits its use.

5.6.2.5 Opiates
Opioid should only be considered as add‐on therapy in some patients who have failed to
respond to all other combination of treatments discussed above. Even with short term use
there is a high risk of addiction, abuse and psychosocial issues. Referral to specialist pain
clinics is recommended. Tramadol is the best studied opiate derivative in neuropathic pain.
It is a centrally acting synthetic opioid which works on both opioid and monoaminergic
pathways. Up to 200 mg/day was found to be effective in the management of painful DN
with efficacy maintained for at least six months [3]. The controlled release oxycodone is
also used in painful diabetic neuropathy and has been subjected to two randomized con-
trolled trials [29]. Recently, the combination of morphine and gabapentin was found to be
more effective than either drug alone, although the gains were modest and in this study
gabapentin alone failed to reduce pain significantly [3].

5.6.2.6 Intravenous Lignocaine

Refractory cases of patients with painful diabetic neuropathy may be treated with intrave-
nous lignocaine at a dose of 5 mg per kg bodyweight over 30 minutes with cardiac monitor-
ing. This has been found to be effective in relieving neuropathic pain for up to six to eight
weeks [30]. This form of treatment is useful in subjects that are having severe pain, which
is not responding to the above agents, although it does necessitate bringing the patient into
hospital for a few hours on a regular basis.

5.6.2.7 Alpha-Lipoic Acid

Infusion of the antioxidant alpha‐lipoic acid at a dose of 600 mg intravenously per day over
a three‐week period, has also been found to be useful in reducing neuropathic pain [30].

5.6.2.8 Treatment Algorithm

Figure 5.1 is a simple treatment algorithm to help practitioners in the pharmacological
management of painful diabetic neuropathy (Figure 5.1) [30]. First line therapies include
all agents with Level A evidence for efficacy: tricyclic antidepressant, duloxetine or an α2δ
subunit of the calcium channel agonist (pregabalin or gabapentin). There is a clear path-
way of progression to second line treatment in combination is first‐line treatment fails.

5.6.2.9 Management of Disabling Painful Neuropathy Not Responding

to Pharmacological Treatment
Despite pharmacotherapy, neuropathic pain can sometimes be extremely severe, interfer-
ing significantly with patients’ sleep and daily activities. These patients may respond to
electrical spinal cord stimulation [30]. This form of treatment is particularly advantageous,
as the patient does not have to take any other pain‐relieving medications, with all their side
effects. Transcutaneous electrical nerve stimulation (TENS) may also be beneficial for the
relief of localized neuropathic pain in one limb.
   ­Reference 101

Painful diabetic neuropathy

Consideration of contraindications and comorbidities

α2-δ agonist SNRI

TCA
(pregabalin or gabapentin) (duloxetine)

If pain control is inadequate and considering contraindications

SNRI or α2-δ agonist TCA or α2-δ agonist

TCA or SNRI
(pregabalin or gabapentin) (pregabalin or gabapentin)

If pain control is still inadequate

Add opioid agonist as combination therapy

Figure 5.1 Pharmacological treatment algorithm for Painful diabetic neuropathy. SNRI, serotonin
norepinephrine reuptake inhibitor, TCA, tricyclic antidepressants [30].

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 105

The Pathway to Ulceration

Aetiopathogenesis and Screening
Andrew J.M. Boulton1,2
1
Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
2
University of Miami, Miami, FL, USA

Coming events cast their shadows before

—Thomas Campbell

6.1 ­Introduction

As the lifetime incidence of foot ulceration in diabetic patients has been estimated to be as
high as 25% [1], understanding the pathways that result in the development of an ulcer
is increasingly important. Although not referring to diabetic foot ulcers when writing
the above lines, the Scottish poet Thomas Campbell’s words can usefully be applied to the
breakdown of the diabetic foot. Ulceration does not occur spontaneously; rather, it is the
combination of causative factors that result in the development of a lesion. There are many
warning signs or ‘shadows’ that can identify those at risk. The famous Boston diabetes
physician Elliot Joslin realized this over 85 years ago when, after observing many clinical
cases of diabetic foot disease, he remarked ‘diabetic gangrene is not heaven‐sent, but earth‐
born’ [2]. Thus, it is not an inevitable consequence of having diabetes that foot ulceration
will eventually occur: ulcers invariably occur as a consequence of an interaction between
specific pathologies in the lower limb and environmental hazards.
Those various pathologies that affect the feet and ultimately interact to increase
­vulnerability to ulceration will be considered in this chapter. A clear understating of the
aetiopathogenesis of ulceration is essential if we are to succeed in reducing the incidence
of foot ulceration, and ultimately amputations. Although some countries such as Germany
have achieved a reduction in diabetes‐related lower limb amputations in recent years [3],
this has not been a universal finding. In England, for example, no decrease in the incidence
of amputations could be observed in the 5 years 2004–2008 [4]. As the vast majority of
amputations are preceded by foot ulcers [5], a thorough understanding of the causative
pathways to ulceration is essential if we are to reduce the depressingly high incidences of

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
106 6 The Pathway to Ulceration

ulceration and amputation. Moreover, as lower limb complications are the commonest
­precipitants of hospitalization of diabetic patients in most countries, there are potential
economic benefits to be gained from preventative strategies, as noted in the previous chap-
ters. Potential economic savings resulting from a number of programmes established in
England were outlined by Kerr in a 2017 Diabetes UK report [6] as well as in Chapter 2 of
this volume. Indeed, prevention of foot ulceration results in substantial savings as 90% of
all the costs of diabetic foot disease are related to ulcer costs. Finally, in the future, it is pos-
sible that smart technology might help in the reduction of foot ulceration, as evidenced by
a recent preliminary study by Frykberg et al. [7].
The breakdown of the diabetic foot traditionally has been considered to result from an
interaction of peripheral arterial disease (PAD), peripheral neuropathy, and some form of
trauma. More recently, other contributory causes, such as psychosocial factors (Chapter 8)
and abnormalities of pressures and loads under the foot [5], have been implicated. The
interaction between neuropathy and foot pressure abnormalities should be considered and,
although covered in great detail in Chapter 14, the importance of vascular disease will be
discussed briefly. There is no compelling evidence that infection is a direct cause of ulcera-
tion: it is likely that infection becomes established once skin breaks occur, and so this topic
will not be considered here. Detailed discussion of infection can be found in Chapter 16.

6.2 ­Peripheral Arterial Disease (PAD)

A number of large epidemiological studies have confirmed the frequency of all forms
of ischaemic vascular disease in diabetes [8, 9]. The Diabetes Audit and Research in
Tayside Scotland (DARTS) study from Scotland, for example, reported the annual
incidence for the development of PAD in diabetic patients to be 5.5/1000 patients in
those with type 1 diabetes, and 13.6/1000 in type 2 diabetes [9]. In the US National
Health and Nutrition Examinations Survey, 1999–2000, the prevalence of PAD in the
general population was 4.3%, but having diabetes was positively associated with prev-
alent PAD (odds ratio 2.83) [10]. PAD tends to occur at a younger age in diabetic
patients and is more likely to involve distal vessels. Reports from the United States
and Finland have confirmed that PAD is a major contributory factor in the pathogen-
esis of foot ulceration and subsequent major amputations [11, 12]. In the assessment
of PAD, simple clinical assessment of the distal circulation and bedside investigations
of the circulation can be useful in the assessment of outcome, although the quality of
studies evaluating these techniques is poor [13].
In the pathogenesis of ulceration, PAD itself, in isolation, rarely causes ulceration: as will
be discussed for neuropathy, it is the combination of risk factors with minor trauma that
inevitably leads to ulceration (Figure 6.1). Thus, minor injury and subsequent infection
increase the demand for blood supply beyond the circulatory capacity, and ischaemic ulcera-
tion and the risk of amputation ensue. Early identification of those at risk and education in
good foot care habits are therefore potentially protective. In recent years, neuroischaemic
ulcers in which a combination of neuropathy and PAD exists in the same patient, together
with some form of trauma, are becoming increasingly common in diabetic foot clinics.
Whereas at the time of publication of the first edition of this volume (1987), neuropathic
 6.3 ­Diabetic Neuropath 107

Dlabetes melltus

Somatic sensory Somatic motor Peripheral vascular

Autonomic neuropathy
neuropathy neuropathy disease

Decreased pain, t° and Small muscle Decreased

wasting sweating Altered blood flow
proprioception

Dry skin Distended loot veins:

Foot deformities
‘Warm feet’

Increased foot pressures callus

Foot at risk

Repetitive trauma:
e.g. III-fitted shoes

Foot ulcer

Figure 6.1 Pathways to diabetic foot ulceration.

ulcers were most frequently seen in diabetic foot clinics, this has changed in the twenty‐first
century, with neuroischaemic ulcers now being the commonest in most clinics.
Although the United Kingdom Prospective Diabetes Study (UKPDS) suggested that tight
control of blood glucose and blood pressure might influence the development of certain
cardiovascular end points such as stroke and sudden death, statistical evidence that these
influence the progression of PAD was not forthcoming [14]. However, educational strate-
gies aimed at the cessation of smoking and control of dyslipidaemia therefore remain of
paramount importance. Moreover, in view of the trends observed in the UKPDS, optimal
glycaemic and blood pressure control should be aimed for.

6.3 ­Diabetic Neuropathy
As discussed in Chapter 5, the diabetic neuropathies represent the commonest of the long‐
term complications of diabetes, affect different parts of the nervous system and may pre-
sent with diverse clinical manifestations [15]. Most common amongst the neuropathies are
chronic sensorimotor distal symmetric polyneuropathy and the autonomic neuropathies.
It is the common chronic sensorimotor neuropathy and peripheral autonomic sympathetic
neuropathy that together play an important part in the pathogenesis of ulceration, and
these will be discussed in some detail. The association between peripheral neuropathy and
foot ulceration has been recognized for many years: Pryce, a surgeon working in Nottingham
over 120 years ago, remarked that ‘it is abundantly clear to me that the actual cause of the
108 6 The Pathway to Ulceration

perforating ulcer was a peripheral nerve degeneration’, and ‘diabetes itself may play an
active part in the causation of the perforating ulcers’.

6.3.1 Sensorimotor Neuropathy

Chronic sensorimotor neuropathy, which commonly occurs in both major types of ­diabetes,
may be defined as ‘the presence of symptoms and/or signs of peripheral nerve dysfunction
in people with diabetes after exclusion of other causes’. The diagnosis cannot be made
without a careful clinical examination of the lower limbs, as absence of symptoms can
never be equated with absence of signs [15].
The onset of chronic neuropathy is gradual and insidious, and indeed, on occasions, the
initial symptoms may go unnoticed by patients. Typical symptoms, which may be present
in up to half of all patients, include paraesthesia, hyperaesthesia, and sharp stabbing,
shooting and burning pain, all of which are prone to nocturnal exacerbation. Whereas in
some patients these uncomfortable symptoms predominate, others may never experience
any symptoms. Clinical examination usually reveals a sensory deficit in a stocking distribu-
tion, and signs of motor dysfunction, including small muscle wasting and absent ankle
reflexes, are usually present [15]. A particularly dangerous situation, originally described
by J.D. Ward, is the ‘painful–painless leg’ in which the patient experiences painful or
­paraesthetic symptoms, but on examination has severe sensory loss to pain and propriocep-
tion; such patients are at great risk of painless injury to their feet.
The threshold of sensation that protects normal feet holds a very delicate balance. The pur-
pose of pain sensation as described by Brand [16] is not to cause pain but to enable the body
to use its strength to the maximum short of damage. Thus, a person who has lost some pain
sensation has not totally lost the ability to feel pain – he simply feels pain at a higher level of
stress. Thus it takes more pressure or temperature or more prolonged ­ischaemia before the
residual nerve fibres are activated and warn higher centres. It must therefore be emphasized
that neuropathic ulceration may occur in patients who still have some ability to perceive
stimuli to various modalities. It is extremely difficult in practice to define exactly what a ‘sig-
nificant’ loss of sensation is, or at what level of sensory loss a patient’s foot becomes ‘at risk’.
There is a spectrum of symptomatic severity in sensorimotor neuropathy: at one extreme,
patients experience severe symptoms whereas others experience mild symptoms or even
none at all. Thus, whereas a history of typical symptoms is strongly suggestive of a diagno-
sis of neuropathy, absence of symptoms cannot exclude neuropathy and must never be
equated with a lack of foot ulcer risk. Therefore, assessment of foot ulcer risk must always
include a careful foot examination whatever the history [15, 16].

6.3.2 Peripheral Sympathetic Autonomic Neuropathy

Sympathetic autonomic neuropathy affecting the lower limbs leads to reduced sweating
and results in both dry skin that is prone to crack and stroke or fissure, and also to increased
blood flow (in the absence of large vessel PAD) with arterio‐venous shunting leading to the
warm foot. The complex interactions of sympathetic neuropathy and other contributory
factors in the causation of foot ulcers are summarized in Figure 6.1.
The warm, insensitive, and dry foot that results from a combination of somatic and auto-
nomic dysfunction often provides the patient with a false sense of security, as most patients
 6.5 ­Other Risk Factors for Foot Ulceratio 109

still perceive vascular disease as the main cause of ulcers. It is such patients who may pre-
sent with insensitive ulceration, as they have truly painless feet. Perhaps, the highest risk
foot is the pulse‐less insensitive foot, because it indicates somatic and autonomic neuropa-
thy together with PAD.

6.4 ­Neuropathy: The Major Contributory Factor in Ulceration

Cross‐sectional data from established UK foot clinics in London and Manchester ­presented
in the second edition of this volume suggested that neuropathy was present in up to 90%
of foot ulcers in patients attending physician – or podiatrist – led services. Thus, most foot
ulcers were considered to be of neuropathic or neuroischaemic aetiology. Confirmation of
these facts in recent years has come from several European and North American studies.
Patients with sensory loss appear to show an increase in risk of developing ulcers of up to
sevenfold, compared with non‐neuropathic, diabetic individuals [17–19]. In the large
North‐West Diabetes Foot Care Study, for example, a cohort of 10 000 patients was
­followed for 2 years in the community [19]. Whereas the overall incidence of new foot
ulceration in the cohort was 2.2%, when divided into those with and without neuropathy
at baseline, the annual incidence of ulceration was 1.1% in those without neuropathy
compared with greater than 6% in those with neuropathy. Other prospective trials have
confirmed the pivotal role of both large‐fibre (e.g. proprioceptive deficits) and small‐fibre
(e.g. loss of pain and temperature sensation) neurological deficits in the ­pathogenesis of
ulceration [17–20]. Poor balance and instability are also increasingly being recognized as
troublesome symptoms of peripheral neuropathy, presumably secondary to propriocep-
tive loss [21]. The relationship between sway, postural instability, and foot ulceration has
also been confirmed.
Considering the above data, there can be little doubt that neuropathy causes foot ulcers with
or without ischaemia, but it must be remembered that the neuropathic foot does not spontane-
ously ulcerate; it is the combination of neuropathy and either extrinsic factors (such as ill‐fitting
footwear) or intrinsic factors (such as high foot pressures, Chapter 6) that results in ulceration.
The other risk factors that are associated with ulceration will now be considered.

6.5 ­Other Risk Factors for Foot Ulceration

6.5.1 Age and Duration of Diabetes

The risk of ulcers and amputation increases two‐ to fourfold with both age and duration of
diabetes [22]. The relationship of diabetes duration to prevalence of ulceration and ampu-
tation appears to be similar for people with both type 1 and type 2 diabetes.

6.5.2 Sex
The male sex has been associated with a 1.6‐fold increased risk of ulcers [19, 22] and
an even higher risk of amputation [22] in most studies of people with type 2 diabetes. The
mechanism by which men are at greater risk of these complications is yet to be explained.
110 6 The Pathway to Ulceration

6.5.3 Previous Foot Ulceration

Several studies have confirmed that foot ulceration is most common in those patients with
a past history of similar lesions or amputation, and also in patients from a poor social back-
ground [22]. Indeed, in many diabetic foot clinics, more than 50% of patients with new foot
ulcers have a past history of similar problems. In one randomized controlled trial, Litzelman
found that a history of an ulcer increased the risk of new ulceration 13‐fold [20]. In another
prospective study, the risk of ulceration was highly associated with a history of previous
ulcers (odds ratio 56.8) [23]. Similarly, a history of prior ulceration is associated with a two‐
to 10fold higher risk of amputation [22].

6.5.4 Other Diabetic Microvascular Complications

It has been recognized for many years that patients with retinopathy and/or renal impair-
ment are at increased risk of foot ulceration. However, it is now confirmed that patients at
all stages of diabetic nephropathy, even microalbuminuria, have an increased risk of foot
ulceration [24]. Indeed, dialysis treatment is an independent risk factor for foot ulceration
in patients with diabetes [25].

6.5.5 Race
Data from cross‐sectional studies in Europe suggest that foot ulceration is commoner in
Europid subjects when compared to groups of other racial origins. Data from the North‐
West Diabetes Foot Care Study showed that the age‐adjusted prevalence of diabetic foot
ulcers (past or present) for Europeans, South Asians and African Caribbeans was 5.5, 1.8
and 2.7%, respectively [26]. The reasons for these ethnic differences certainly warrant fur-
ther investigation. In contrast, in the southern United States, ulceration was much more
common in Hispanic Americans and native Americans than in non‐Hispanic Whites [27].
However, there is no suggestion that within Europe the risk is related to any geographical
differences: Veves et al., for example, showed no differences in risk factors for ulceration
according to location, for different European centres [28].

6.5.6 Motor Neuropathy

Although the commonest neuropathy of diabetes is ‘chronic sensorimotor neuropathy’,
most reviews focus exclusively on the sensory components. Thus, special mention is made
here of the motor component: small muscle wasting in the feet is common in neuropathy,
and atrophy of foot muscles is closely related to the severity of neuropathy [29]. Moreover,
small muscle dysfunction secondary to neuropathy may contribute to ulcer risk through
altered gait and foot pressure changes.

6.5.7 Oedema
The presence of peripheral oedema impairs local blood supply and has been associated
with increased risk of ulceration [30].
 6.6 ­Assessment of Foot Ulcer Ris 111

6.5.8 Callus
The presence of plantar callus, especially in the neuropathic foot, is associated with an
increased risk of ulceration: in one study, the risk was 77‐fold in the cross‐sectional part,
whereas in the prospective follow‐up, ulceration occurred only at sites of callus, represent-
ing an infinite increase in risk [31].

6.5.9 Deformity
Any deformity occurring in a diabetic foot with other risk factors, such as prominence of
the metatarsal heads, clawing of the toes, Charcot prominences or hallux valgus, increases
ulcer risk. Evidence to support this statement comes from the prospective North‐West
Diabetes Foot Care Study in which foot deformities were independently related to the risk
of new foot ulcers [19].

6.5.10 Transplantation
There is increasing evidence that diabetic patients remain at high risk of foot problems
after successful renal, pancreas, and especially simultaneous pancreas kidney (SPK)
­transplantation [32, 33]. Most patients undergoing these procedures have advanced com-
plications including neuropathy. Life on dialysis is frequently miserable, and after renal or
SPK transplants, these patients have a new lease of life but remain at significant high risk
of foot complications. Both Charcot neuroarthropathy and foot ulceration occur in these
very high risk patients: one study reported that 10% of patients develop foot complications
in the first few years following pancreas transplantation [32].

6.6 ­Assessment of Foot Ulcer Risk

For one mistake made for not knowing, ten mistakes are made for not looking
—J.A. Lindsay

The above aphorism could have been written specifically for diabetic foot problems, as
many foot lesions are missed because the clinician fails to examine the feet. Paul Brand
(1914–2003) emphasized this when he was asked, at a US Department of Health Conference,
to recommend how amputations could be reduced in diabetic patients. Expecting an
answer promoting vascular surgery or modern medications, the questioner was surprised
at the answer, ‘remove the shoes and socks and examine the feet every time you see a
patient with diabetes’ [16].
The traditional model of disease is that a patient goes to the doctor with symptoms,
treatment is then prescribed and the patient recovers. As this cannot apply to insensate
feet, health care professionals have difficulty comprehending the diabetic foot syn-
drome: they find it difficult to take the initiative and look for early lesions or warning
signs of imminent breakdown. Many doctors regard these patients as stupid – how can a
sensible individual walk on a swollen red foot with an active ulcer? What we must ­realize
112 6 The Pathway to Ulceration

Table 6.1 Screening techniques for identifying the ‘at-risk’ foot.

Primary care Secondary care Clinical research

History (symptoms of neuropathy/PVD) +++ +++ +

Clinical exam +++ +++ +++
Monofilament/ITT +++ ++ ++
Vibration perception ++ ++ +++
Quantitative sensory tests − + ++
Electrophysiology − − ++
Pressuremat (e.g. PressureStat) ++ ++ ++
Quantitative foot pressure − + ++

+++, recommended; ++, useful if available; +, occasionally required; −, not recommended.

ITT = Ipswich Touch Test.

is that an insensitive foot not only is painless, but also does not feel as if it belongs to the
individual [16]. In screening for ‘at‐risk’ feet, it is our job to identify patients at risk of
ulceration and help them understand and cope with this health state and thus avoid
exposure to environmental hazards that may result in injury (often unperceived) and
eventual breakdown.
As with other microvascular complications, there may be no symptoms to suggest to the
patient that they have foot problems. The concept of the ‘annual review’ for diabetic
patients is now well established and the American Diabetes Association published a report
detailing what should be included in the comprehensive foot examination and risk assess-
ment [34]. Thus, all patients should be screened for retinopathy, hypertension, nephropa-
thy, and risk of foot lesions, annually. For the foot, the following are recommended
according to the level of care (Table 6.1).

1) History – important in the annual review

a) Neuropathic symptoms?
b) Past history of ulcer?
c) Other diabetic problems, especially retinopathy/impaired vision/transplantation?
d) History of claudication/rest pain/vascular surgery?
e) Home circumstances – e.g. living alone?
2) Examination – essential in the annual review
a) Inspection: shoes and socks must be removed
i) Skin status: colour, thickness, dryness, cracking?
ii) Sweating?
iii) Infection: check between the toes as well.
iv) Ulceration?
v) Deformity, e.g. Charcot changes or clawing of the toes?
vi) Foot shape.
vii) Small muscle wasting?
 6.6 ­Assessment of Foot Ulcer Ris 113

Table 6.2 The modified neuropathy disability score.

Neuropathy Disability Score (NDS)

Right Left

Vibration perception threshold

128‐Hz tuning fork; apex of big toe; normal = can
distinguish vibrating/not vibrating
Temperature perception on dorsum of the foot
Use tuning fork with beaker of ice/warm water; Normal = 0
normal = can distinguish hot from cold Abnormal = 1
Pinprick
Apply pin proximal to big toenail just enough to deform
the skin; trial pair = sharp, blunt; normal = can
distinguish sharp/not sharp
Achilles reflex
Present = 0
Present with
reinforcement = 1
Absent = 2
NDS total out of 10

Source: Reproduced with permission from the American Diabetes Association, from Ref. [15].
Copyright © 2004 American Diabetes Association. From Boulton et al. [51].

viii) Skin temperature: compare the feet. A unilateral, warm swollen foot with
intact skin would suggest the possibility of acute Charcot neuroarthropathy.
Moreover, prior to neuropathic ulceration there would be a local increase in
temperature [35].
ix) The patient’s footwear and gait should also be assessed. Walking without a limp
with a plantar ulcer is diagnostic of neuropathy.
b) Neurological assessment
i) Neuropathy can easily be documented by a simple clinical exam of large‐fibre
function (e.g. 128‐Hz tuning fork for vibration), small‐fibre function (e.g. pin-
prick, hot/cold rods) and ankle reflexes. A simple composite score comprising
these measures (Table 6.2) has been shown to be useful in the prediction of those
at risk of future ulceration [19].
ii) 10‐g monofilament: This tests pressure perception and is frequently used to
assess foot ulcer risk status [36]. Although simple to perform, general ­agreement
is lacking as to which site should be tested and not all filaments accurately
assess pressure at 10 g [37]. Moreover, the number of sites that should be tested
is unknown: for example, the 128‐Hz tuning fork vibration assessment tested
at two sites was shown to be as sensitive as the monofilament tested at eight
sites [38].
114 6 The Pathway to Ulceration

iii) Ipswich Touch Test (ITT): This is a simple test that involves touching the tips of
the first, third, and fifth toes of both feet with the examiner’s index finger [39]
reduced sensation is defined as ≥2 insensate areas. This test was shown to have
almost perfect agreement with the monofilament, and also can be used by rela-
tives or caregivers to assess people with diabetes in the home setting [40].
c) Vascular assessment
i) Posterior tibial and dorsalis pedis pulses should be palpated.
ii) Bedside assessment of the circulation using a Doppler ultrasound probe can be
useful. However, the presence of diabetes and neuropathy make the usual tests
such as the ankle pressure index less efficacious: wave form analysis and pres-
sures are more effective [41].
3) Other assessments
a) Quantitative sensory testing (QST)
i) Vibration assessment: The biothesiometer, neurothesiometer, and vibration
perception threshold meters are simple, hand‐held tests of vibration perception
that can easily be used in the outpatient setting: loss of vibration as assessed
with these instruments is strongly predictive of subsequent ulceration [18].
More recently, the Vibratip (McCallan Medical, Nottingham, UK), a small hand
held, pocket‐sized, battery powered disposable device that assesses vibration over
the hallux, has been shown to correlate highly significantly with other tests
including the ITT [42].
ii) Temperature perception: A hand‐held instrument, the NeuroQuick [43], that
tests cold sensation is available.
iii) Other QST instruments: Other more elaborate equipment to assess distal sensory
function are available [15]. However, most of these are expensive and time con-
suming and are restricted to clinical research usage.
iv) Electrophysiology: Although nerve conduction studies strongly predict future
ulcers [44], its use is generally restricted to clinical research studies.
v) Sweat indicator test: Sympathetic autonomic neuropathy in the lower limb results in
dry skin and callus formation. A simple non‐invasive sweat indicator test (Neuropad,
Trigocare, Wiehl‐Drabenderhöhe, Germany) can detect the absence of sweating when
the patch is applied to the foot of a neuropathic patient [45]. This is strongly associated
with risk of foot ulceration, and Neuropad can also be used as an educational aid as the
patient can see the lack of colour change when applied to the foot, in contrast, for
example, when it is applied to the upper limb or any area of normal sweating.
b) Foot pressure studies
i) Simple semi‐quantitative mat systems: PressureStat is a simple, inexpensive,
semi‐quantitative foot print mat that takes a minute or two to measure plantar
pressures. Images can be identified immediately (Figure 6.2) and as higher pres-
sure areas are darker, this provides a powerful educational tool to help patients
understand which areas of their feet are at particular risk [46].
ii) Detailed foot pressure analysis: A number of complex mats and in‐shoe systems
are available for foot pressure analysis. These are covered in Chapter 7.
4) Guidelines – a number of guidelines on foot assessment are available as published
reviews [15, 22, 34].
 6.6 ­Assessment of Foot Ulcer Ris 115

Figure 6.2 An example of a PressureStat Foot Print. The darker areas represent higher foot
pressures.
116 6 The Pathway to Ulceration

6.7 ­The Pathway to Ulceration

It is the combination of two or more risk factors that ultimately results in diabetic foot
ulceration. Both Pecoraro et al. [11] and later Reiber et al. [30] have taken the Rothman
model for causation and applied this to amputation and foot ulceration in diabetes.
The model is based upon the concept that a component cause (e.g. neuropathy) is not
sufficient in itself to lead to ulceration, but when the component causes act together,
they result in a sufficient cause, which will inevitably result in ulceration (Figure 6.3).
In their study of amputations, Pecoraro et al. [11] described five component causes
that lead to amputation: neuropathy, minor trauma, ulceration, faulty healing and
gangrene.
Reiber et al. subsequently applied this model to foot ulceration, and a number of causal
pathways were identified: the commonest triad of component causes, present in 63% of
incident cases, was neuropathy, deformity, and trauma (Figure 6.4). Oedema and ischae-
mia were also common component causes.
Other simple examples of two‐component pathways to ulceration are neuropathy and
mechanical trauma, e.g. standing on a nail (Figure 6.5), ill‐fitting footwear (Figure 6.6);
neuropathy and thermal trauma; and neuropathy and chemical trauma, e.g. the inappro-
priate use of chemical ‘corn cures’. Similarly, the Rothman model can be applied to neu-
roischaemic ulceration, where the three component parts comprising ischaemia, trauma,
and neuropathy are often seen [11, 30].

SUFFICIENT CAUSE:
E D
• Inevitably produces an ulcer

• Restricted to the minimal

A C number of component
B causes required for
B a foot ulcer

COMPONENT CAUSE:

• Not sufficient in itself

• Removal or blocking renders action of

other components insufficient

Figure 6.3 Diagram of sufficient and component causes of diabetic foot ulcers. a–e
represent causes that are not sufficient in themselves but that are the required components
of a sufficient cause that will inevitably produce the affect. (Source: From [30]. Reprinted with
permission from The American Diabetes Association. Copyright © 1999 American Diabetes
Association.)
 6.7 ­The Pathway to Ulceratio 117

U
N N N N
D T T

Neuropathy Deformity Minor trauma

Baseline Pathopysiologic Environmental Time Ulceration

pathology involvement event

Accumulation of component Completed

causes to form a sufficient cause causal chain
to ulcer

Figure 6.4 The commonest causal pathway to incident diabetic foot ulcers. (Source: From [30].
Reprinted with permission from The American Diabetes Association. Copyright © 1999 American
Diabetes Association.)

Figure 6.5 Radiograph of patient presenting with a recurrent discharging heel lesion. On enquiry,
the patient remembered some trauma to the heel but did not realize that he had part of a needle
in the subcutaneous tissue under the calcaneum – an example of a traumatic ulcer in the
insensitive foot, which could have been prevented by wearing appropriate footwear.
118 6 The Pathway to Ulceration

Figure 6.6 Inappropriate footwear for a female patient with insensitive feet (top) that resulted in
toe lesions (bottom).

6.8 ­Mechanical Factors and Neuropathic Foot Ulceration

The insensitive neuropathic foot does not ulcerate spontaneously: traumatic or extrinsic
ulcers result as a consequence of trauma to the insensitive foot, as shown in Figure 6.6. In
contrast, intrinsic or pressure ulcers occur as a result of pressure that would not normally
cause ulceration, but which, because of intrinsic abnormalities in the neuropathic foot,
 6.8 ­Mechanical Factors and Neuropathic Foot Ulceratio 119

Figure 6.7 The high-risk neuropathic foot (plantar and lateral views). This foot displays a marked
prominence of the metatarsal heads with clawing of the toes and is at high risk of pressure-induced
ulceration.

leads to plantar ulceration when repetitively applied. As stated in the next chapter,
­abnormalities of pressures and loads under the diabetic foot are very common. Both
­prospective and cross‐sectional studies have confirmed that high plantar pressures are a
major aetiological factor in neuropathic foot ulceration [5, 47]. Pressure ulcers tend to
occur under areas such as the metatarsal heads, as a result of repetitive pressure ­application
during walking. Callus tissue that forms under the dry foot (as a consequence of autonomic
neuropathy) may itself further aggravate the problem. An example of a foot at high risk of
intrinsic neuropathic foot ulceration, with insensitivity, prominent metatarsal heads,
clawed toes and resultant high foot pressure, is provided in Figure 6.7. Evidence suggests
that high foot pressures occur early in the natural history of diabetes, often before clinical
neuropathy is apparent [48].
120 6 The Pathway to Ulceration

Two additional component causes for intrinsic foot ulcers are callus and limitation of
joint mobility. This latter abnormality, originally described in the hand, also occurs in the
feet and contributes to abnormalities of foot pressure.
The five component causes leading to intrinsic foot ulcers are therefore somatic periph-
eral neuropathy, sympathetic peripheral neuropathy, limited joint mobility, callus and high
foot pressure. There is therefore potential for preventing such ulcers: callus can be removed
by the podiatrist; high foot pressures can be reduced by callus removal, protective insoles
and hosiery; and the incidence of neuropathy can be reduced by near‐normoglycaemia from
the time of diagnosis of diabetes. Thus, many if not most neuropathic and neuroischaemic
ulcers are potentially preventable.

6.9 ­The Patient with Sensory Loss

It should now be possible to achieve a significant reduction of foot ulcer and amputation in
diabetes. Guidelines now exist for the diagnosis and management of neuropathy [15] and
foot problems [34, 49, 50]. However, much work is still required in the assessment and
management of psychosocial factors (Chapter 11) and, as is well known, guidelines will be
of use only if properly implemented.
However, a reduction in neuropathic foot problems will be achieved only if we remember
that patients with insensitive feet have lost their warning signal – pain – that ordinarily
brings the patients to their doctors. Thus, as stated earlier, the care of a patient with no pain
sensation is a new challenge for which we have no training. It is difficult for us to under-
stand, for example, that an intelligent patient would buy and wear a pair of shoes three
sizes too small and come to our clinic with an extensive shoe‐induced ulcer (Figure 6.6).
The explanation however is simple: with reduced sensation, a very tight fit stimulates the
remaining pressure nerve endings, and this is interpreted as a normal fit – hence the com-
mon complaint when we provide patients with custom‐designed shoes is ‘these shoes are
too loose’. We can learn much about the management from the treatment of patients with
leprosy [16]; if we are to succeed, we must realize that with loss of pain there is also dimin-
ished motivation in the healing of, and prevention of, injury.

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20 Litzelman, D.K., Marriott, D.J., and Vinicor, F. (1997). Independent physiological
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compromises balance during daily activities. Diabetes Care 38: 1116–1122.
22 Boulton, A.J.M. (2016). The diabetic foot. In: Endotext (internet) (eds. L.J. DeGroot, G.
Chrousos, K. Dungan, et al.). South Dartmouth, MA: MD Text.com, Inc.
23 McNeely, M.J., Boyko, E.J., Ahroni, J.H. et al. (1995). The independent contributions of
diabetic neuropathy and vasculopathy in foot ulceration. Diabetes Care 18: 216–219.
24 Fernando, D.J.S., Hutchinson, A., Veves, A. et al. (1991). Risk factors for non‐ischaemic
foot ulceration in diabetic nephropathy. Diabet. Med. 8: 223–225.
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25 Ndip, A., Rutter, M.K., Vileikyte, L. et al. (2010). Dialysis treatment is an independent risk
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1811–1816.
26 Abbott, C.A., Garrow, A.P., Carrington, A.L. et al. (2005). Foot ulcer risk is lower in south
Asian and African‐Caribbean compared to European diabetic patients in the UK: the
north‐west diabetes Footcare study. Diabetes Care 28: 1869–1875.
27 Lavery, L.A., Armstrong, D.G., Wunderlich, R.P. et al. (2003). Diabetic foot syndrome:
evaluating the prevalence and incidence of foot pathology in Mexican‐Americans and
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28 Veves, A., Uccioli, L., Manes, C. et al. (1996). Comparison of risk factors for foot ulceration
in diabetic patients attending teaching hospital out‐patient clinics in four different
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29 Anderson, H., Gjerstad, M.D., and Jakobsen, J. (2004). Atrophy of foot muscles: a measure
of diabetic neuropathy. Diabetes Care 27: 2382–2385.
30 Reiber, G.E., Vileikyte, L., Boyko, E.J. et al. (1999). Causal pathways for incident lower
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31 Murray, H.J., Young, M.J., and Boulton, A.J.M. (1996). The relationship between callus
formation, high foot pressures and neuropathy in diabetic foot ulceration. Diabet. Med. 16:
979–982.
32 Seo, D.K., Lee, H.S., Park, J. et al. (2017). Diabetic foot complications despite successful
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33 Garcia‐Barrado, F., Kuypers, P.R., and Matricali, G.A. (2015). Charcot Neuroarthropathy
after simultaneous pancreas‐kidney transplantation: risk factors, prevalence and outcome.
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34 Boulton, A.J.M., Armstrong, D.G., Albert, S.F. et al. (2008). Comprehensive foot
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35 Lavery, L.A., Higgins, K.R., Lanctot, D.R. et al. (2004). Home monitoring of foot skin
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36 Mayfield, J.E. and Sugarman, J.R. (2000). The use of the Semmes‐Weinstein monofilament
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43 Ziegler, D., Siekierka, E.K., Meyer, B. et al. (2005). Validation of a novel screening device
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in diabetic patients with high foot pressure: a prospective study. Diabetologia 35: 660–663.
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 125

Biomechanics of the Diabetic Foot for the Uninitiated

S.A. Bus1 and J.S. Ulbrecht2,3
1
Department of Rehabilitation, Academic Medical Center, University of Amsterdam, Amsterdam Movement Sciences,
Amsterdam, The Netherlands
2
Department of BioBehavioral Health and Medicine, Pennsylvania State University, University Park, PA, USA
3
Mount Nittany Health, State College, PA, USA

7.1 ­Introduction

Biomechanics is the field of research in which forces and their consequences applied to
living tissue are studied. Biomechanics plays an important role in the development and
management of foot complications in diabetes. Foot ulcers that do not heal often do so
because of abnormal biomechanics, and in a foot that may seem normal from the outside,
biomechanical issues are often the cause of abundant callus, foot deformity or foot ulcers
developing. Therefore, for the practising clinician and health care professional it is impor-
tant to understand the basics of foot biomechanics in diabetes to better understand why
foot problems develop or recur, and how they can be best treated.
This chapter discusses several practical biomechanical concepts applied to the diabetic
foot, without getting too sophisticated about biomechanical modelling and tissue engineer-
ing. We will discuss the role of elevated plantar pressures in the development of foot ulcers
in diabetes, which mechanisms lead to high pressures, and the role that biomechanics plays
in different treatment modalities used in the healing and prevention of diabetic foot ulcers.
Regarding prevention, the role of footwear will be discussed, although a more complete
discussion on footwear can be found in Chapter 24.

7.2 ­The Concept of Pressure and its Measurement

Force and stress (or pressure) are directly related to each other. Pressure is the force divided
by the area over which it is applied. This means that when a force is distributed over only a
small area of the foot, the pressure will be high, but when distributed over a large area of
the foot, it will be relatively low. In patients with longstanding diabetes, bony prominences

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
126 7 Biomechanics of the Diabetic Foot for the Uninitiated

Figure 7.1 Example of a system to measure barefoot plantar pressures (left) and in-shoe plantar
pressure (right).

are often present and concentrate the force or load to a small area of the plantar aspect of
the foot whilst walking. As a consequence, the pressures are high at these prominences.
Force and pressure are not visible by the naked eye and therefore abnormal pressures can
be easily overlooked if not quantified. Dr Paul Brand, an orthopaedic surgeon, and his col-
leagues were amongst the first to measure foot pressure in patients with neuropathy and
defined the clinical concept of pressure being the harm done by force [1, 2]. They measured
pressures under the foot in barefoot walking and in shoes in patients with leprosy, in which
the consequences of neuropathy can be very similar to those in diabetes. Later, these pres-
sure measurements became more sophisticated with the introduction of pressure platforms
and insole systems with an array of sensors with which pressure distributions under the
foot could be assessed. Although long applied in diabetic foot research, the measurement
of plantar pressure whilst walking barefoot and inside shoes has become increasingly pop-
ular in clinical practice over the last decade. Figure 7.1 shows some examples of systems for
plantar pressure measurement. So, when we speak about the biomechanics of the diabetic
foot, we most often refer to the relatively high pressures applied to the foot and how these
can be reduced.

7.3 ­The Role of Elevated Plantar Pressure in Foot Ulceration

In the presence of loss of protective sensation (see Chapter 5) that develops because of
peripheral neuropathy, an elevated level of plantar pressure has been identified as a signifi-
cant contributor to the development of foot ulcers in diabetes [3, 4]. The area where the
foot ulcer is present often corresponds with the area of high peak pressure, as shown in a
few examples in Figure 7.2. Such high pressures are usually not seen in healthy feet and if
present would result in pain during ambulation for a person who has adequate sensation.
Such a person would adjust their gait or change footwear, to avoid bearing the high pres-
sures involved. A patient with rheumatoid arthritis may have such high pressures due to
bony prominences in the foot but not develop a foot ulcer because of intact sensation. This
means that high pressure alone is not sufficient for plantar ulceration, and neither is neu-
ropathy. It is the combination of the two that provides the necessary and sufficient condi-
tions for ulceration.
 7.3 ­The Role of Elevated Plantar Pressure in Foot Ulceratio 127

Figure 7.2 Examples of patients with a plantar foot ulcer, where the location of the foot ulcer
corresponds with the area of high peak pressure under the foot, shown as the pink coloured peaks
in the three-dimensional pressure distribution diagrams.

Repetitive application of high plantar pressures to the same tissue on the foot, often
overlying a bony prominence, or otherwise not protected by cushioning subcutaneous tis-
sue, is the most common pathway to ulceration in diabetic patients [5]. In the presence of
loss of protective sensation this is believed to cause tissue damage that begins deep, close
to the bone. Callus frequently forms on the skin surface. A haemorrhage can occur into the
callus. Such a pre‐ulcer can then develop into a full foot ulcer if the pressure on that area
is not taken away. Thus callus over a bony prominence, and particularly a callus with
haemorrhage, is a significant clinical finding.
Another pathway of injury of the insensate foot may be through direct trauma to the foot,
for example because a little stone is present in the shoe without the patient noticing it due
to the neuropathy. Also possible is injury by lower pressures that are applied to the insen-
sate foot for longer continuous periods of time, for example because the patient is hospital-
ized due to diabetic complications. Such ulcers often occur bilaterally on the posterior heel
of the feet.
There is uncertainty about the critical magnitude of plantar pressure that is required for
tissue damage and an ulcer to develop in the insensate foot. Different prediction studies
result in different values of barefoot plantar pressure required [6, 7]. One study suggests
that a peak pressure threshold of 700 kPa in barefoot walking provides the best compromise
between sensitivity and specificity, but neither sensitivity nor specificity are high enough
that one can safely predict the occurrence or prevention of foot ulceration based on this
value. Thus barefoot plantar pressure measurement has so far not been shown to be
128 7 Biomechanics of the Diabetic Foot for the Uninitiated

c­ linically useful in predicting plantar ulceration [8]. In fact it is likely that each patient’s
threshold is different, and is determined by more factors than only barefoot peak pressure,
such as activity level, tissue quality, and, very importantly, the pressure experienced whilst
walking in shoes. The footwear chosen and the in‐shoe pressures that the patient is subject
to, can clearly make the difference between ulceration and no ulceration, and this is an
important variable to consider [4].
To this point we have been discussing the concept and effect of vertical or normal pres-
sures on the foot. The forces exerted parallel to the skin are the shear stress or pressure.
Shear also has the potential to damage tissue by causing a tear [9], and many think that the
development of callus on the foot is primarily the result of shear. Only few relatively small
studies have explored what role shear may have in injuring the insensate foot. Some of the
findings are that shear pressures whilst walking barefoot are higher in diabetic neuropathic
patients than in non‐diabetic controls [9], and in patients with a history of diabetic foot
ulceration compared to those without [10]. Furthermore, the location of peak vertical pres-
sure in the forefoot in diabetic neuropathic subjects may often not correspond with the loca-
tion of peak shear pressure, suggesting that shear may play an additional role in causing foot
ulcers in diabetes [11, 12]. Larger prospective studies will have to confirm what the exact
role of shear is. This should also include the measurement of shear inside the patient’s shoe,
which to date has proven futile because of technical difficulties involved in this.

7.4 ­Mechanisms of Elevated Plantar Pressure

Mechanisms that lead to elevated levels of pressure can be due to intrinsic and extrinsic
factors and also from behavioural factors. Most neuropathic ulcers occur at the toes and
metatarsal heads and these areas are therefore of particular interest in understanding the
causes of elevated plantar pressures.
As intrinsic factors, callus formation, tissue quality and foot deformity are the major fac-
tors in causing elevated plantar pressure [13]. Callus can concentrate pressure, as if it were
a foreign body under the foot, and seems to be the result of both vertical and shear pres-
sures whilst being active. The presence of abundant callus can increase the risk of ulcera-
tion with a factor 10 [14], and the removal of callus has been shown to reduce pressure by
an average 30% [15]. Therefore, in good clinical practice, callus is regularly removed.
Foot deformities that have been shown to increase pressure are claw toes and hammer
toes, hallux valgus, Charcot foot deformity, and partial foot amputation [16–18]. Clawing
of the toes has been shown to lead to the plantar fad pads protecting the metatarsal heads
to be displaced anteriorly, leaving the head ‘exposed’ by inadequate thickness of the tissue
underneath the bone [19]. These prominent metatarsal heads can be palpated through the
thin layer of tissue remaining overlying the bone. Clawing of the toes, the degree of ante-
rior displacement of fat pad tissue and fat pad tissue thickness have been strongly associ-
ated with elevated plantar pressure [16]. Toe tips are not usually weight bearing with little
soft tissue overlying the bone. When toes are hammered, toe tips become weight bearing
and often callus develops at these toe tips, with pressures being higher there as well.
Charcot fractures of the midfoot can typically result in a ‘rocker bottom’ foot. Just like toe
tips, the midfoot is not evolved to bear heavy plantar loads with only minimal sub‐cutaneous
 7.4 ­Mechanisms of Elevated Plantar Pressur 129

tissue present. As a result, pressure can be extremely high in this area when patients bear
weight on that part of the foot, as the example in Figure 7.2 shows [17].
The range of motion in the joints of the foot and ankle is decreased in many patients with
diabetes. This is not a neuropathic condition, but an effect of non‐enzymatic glycosylation
whereby the collagen in joint capsules is stiffened by the glycosylation process [20]. The
consequences of limited joint mobility in the metatarsal‐phalangeal, sub‐talar, and talo‐
crural joints is an increased pressure under the forefoot. The most problematic joint in this
regard is the first MTP joint [21], with patients having a neuropathic ulcer underneath the
hallux often showing reduced dorsiflexion at this joint and high plantar hallux pressures.
Certain surgical procedures that are intended to reduce pressure in regions of high ulcer-
ation risk can have a secondary effect of increasing pressure in other areas. For example,
Achilles tendon lengthening, which is performed to heal recalcitrant forefoot ulcers, can
result in more proximal problems where pressures substantially increase at the heel
because of an altered gait in these patients [22, 23]. Forefoot procedures, such as metatarsal
head resection and amputation of a toe or ray almost by necessity lead to higher pressures
in other forefoot regions that have to bear the load on the foot [24].
The effects of motor neuropathy are often underestimated, but a number of studies have
shown severe atrophy of the intrinsic muscles of the feet (Figure 7.3) [25–27]. This atrophy
alters the biomechanics of the foot, is suggested to be a cause of toe deformity, although
this has not yet been shown convincingly [27], and may lead to instability during standing
and walking.

Non-diabetic control Neuropathic Non-diabetic control Neuropathic

Figure 7.3 Severe atrophy of the intrinsic foot muscles present in diabetic neuropathic patients when
compared to non-diabetic control subjects, as shown on these MRI cross-sectional images [25]. Muscle
atrophy shows as light-grey coloured tissue representing fatty tissue where in the non-diabetic feet
dark-grey coloured muscle tissue is present.
130 7 Biomechanics of the Diabetic Foot for the Uninitiated

Footwear is an important extrinsic factor that can affect plantar pressure and with that
risk of ulceration. Whilst appropriate footwear that can reduce pressure at risk locations in
the foot and can be of great benefit in preventing ulcers, incorrect footwear can actually
cause ulceration – as is discussed further in Chapter 24.
Barefoot walking is not a cause of high plantar pressure but exposes the plantar soft
­tissues to very high pressure and is therefore believed to be a principal cause of plantar
ulceration that is amenable to behavioural intervention. Barefoot pressures can be even
10 times higher than pressures experienced whilst walking in shoes. Several studies have
demonstrated that non‐adherence with therapeutic footwear use increases the risk of
ulceration [4] – though from these studies it is not clear whether non‐adherence with pre-
scribed footwear resulted in using other shoes, barefoot walking or both. Clinical experi-
ence suggests that there are at least some very high risk patients who ulcerate because they
take just a few steps barefoot to go to the bathroom during the night. Some form of
­adequately offloading footwear that is easy to don is required in these cases [28].
The association between walking activity profiles and risk of ulceration is a difficult one.
The more steps a patient takes, the higher the cumulative load on the foot. But surprisingly,
a direct relationship between number of steps per day and risk of ulceration has not
emerged to date [4]. It has been suggested that either a change in level of activity [29] or
variability in activity [4, 30] may be important risk factors for ulceration.
There are some indications that neuropathic patients have altered gait patterns [31, 32],
but it is not yet clear whether this results in elevated plantar pressure. Regardless, patients
with loss of protective sensation will not consciously alter their gait because they feel no
pain developing in high‐pressure areas from too much walking. There is also some evi-
dence that neuropathic patients experience more falls and injuries due to falls than matched
non‐neuropathic diabetic patients [33, 34].

7.5 ­Foot Biomechanics in Treating a Plantar Foot Ulcer

In order to heal a plantar foot ulcer, the pressure acting on the ulcer needs to be reduced by
redistributing the pressure to other regions in the foot or lower leg. Multiple meta‐analyses
and systematic reviews have evaluated the existing literature on the topic of plantar foot
ulcer healing [35–38] and offloading is considered one of the cornerstones of treatment for
plantar foot ulcers [39]. The most effective way to offload the plantar foot is by use of a total
contact cast (TCC) or a knee‐high walker (Figure 7.4) [35, 40]. These devices can reduce
peak pressure in the forefoot by an average 87% compared to standard non‐therapeutic
footwear [40]. This effect is achieved by redistribution of forces not only under the foot to
more proximal regions, but also to the lower leg through the device wall, in addition to
limiting ankle motion by the device [41, 42]. For these reasons, devices that only extend to
the ankle or just above the ankle, such as cast shoes and forefoot offloading shoes, are gen-
erally less effective in offloading the foot with ~40–60% relief in peak pressure compared to
a standard control condition [40, 43, 44].
Surprisingly, whilst there are these significant differences in offloading efficacy between
devices used to support ulcer healing, the direct association between the degree of offload-
ing and healing of a foot ulcer has hardly been studied [45].
 7.5 ­Foot Biomechanics in Treating a Plantar Foot Ulce 131

Extra-depth shoes (n = 1)

Custom molded insert (n = 6)

Athletic shoe (n = 2)

Rocker shoe (n = 2)

Cast shoe (n = 2)

Felted foam dressing (n = 1)

Low-cut walker (n = 3)

Half shoe / FOS (n = 4)

Bivalved TCC (n = 2)

Removable walker (n = 5)

TCC (n = 4)

0 10 20 30 40 50 60 70 80 90 100

Figure 7.4 Offloading capacity of different modalities and devices that are used for the prevention
and treatment of plantar foot ulcers in diabetes. The x-axis represents the percentage of offloading
found at the first metatarsal head in comparison to a control shoe condition [40].

The largest available evidence base about offloading in treating foot ulcers is for the treat-
ment of neuropathic plantar foot ulcers that are not complicated by infection or ischemia
[35]. Very few data are available addressing offloading treatment of more complicated plantar
ulcers, even though these ulcers also require offloading; one study found that whilst percent
healing was less for infected and ischemic ulcers, offloading in a TCC was still effective [46].
The latest international guidelines on offloading treatment also include some considerations
in this area that are important for the practitioner to know [47].
In general, non‐removable offloading is more effective than removable offloading, both
in terms of healing proportions and time to healing. The difference presumably stems from
the degree of adherence to the device used. One study found that patients used their pre-
scribed removable knee‐high walker for an average of only 29% of their total daily number
of steps [48]. This is an important issue to discuss with the patient when discussion offload-
ing options or when irremovable offloading is not an option.
To this point one RCT showed similar healing rates between the TCC and a removable
walker – but unfortunately the authors did not provide information about how they promoted
adherence in this study [49]. In any case, whilst the TCC has long been considered by many
the gold standard treatment for offloading foot ulcers, these findings confirm that offloading
in a removable device is sufficient when this is used for most/all steps taken [47]. For locations
where casting, or adequate skills in casting, are not available this gives the opportunity to still
provide evidence‐based offloading. Adverse effects of wearing TCCs that may occur and
should be considered are muscle atrophy with prolonged use, reduced activity level, difficulty
with sleeping or driving a car, and iatrogenic ulcers due to poor casting [47].
Forefoot offloading shoes, cast shoes and custom‐made temporary shoes may be effective
in healing neuropathic forefoot ulcers although their efficacy has often only been assessed
in retrospective studies [50–52].; confirmation in prospective analyses is required.
132 7 Biomechanics of the Diabetic Foot for the Uninitiated

Between 80 and 90% of plantar neuropathic ulcers heal in 12 weeks when effectively
offloaded, on average in 6–8 weeks.
As alluded to above, several different surgical procedures can also be used in healing foot
ulcers because they can effectively relief forefoot peak pressures and these include Achilles
tendon lengthening, metatarsal head resections and liquid silicon injections [22, 24, 53].
However, effects may only be temporary in some cases. However, such surgical interven-
tions may have only limited additional value in ulcer healing compared to non‐surgical
treatment [35]. The effect of digital flexor tenotomy in healing apex toe ulcers has only
been assessed in retrospective case series; from the success rates found for proportion of
ulcers healed and time to healing, this seems a promising technique [35].
Callus removal can reduce peak pressures by as much as 30%, although durability of such
relief is unknown [15, 54].
Non‐plantar ulcers are easier to heal than plantar ulcers, though the principles are the
same: avoidance of ongoing mechanical injury, in this case usually from footwear.

7.6 ­Biomechanical Issues in Preventing a Foot Ulcer

When a foot ulcer is not present but the patient has loss of protective sensation and a foot
deformity or a history of foot ulceration, pressures can be high and needs to be offloaded to
prevent a foot ulcer from developing. For this, orthotic treatment is the most commonly
applied biomechanical modality, including therapeutic footwear, custom‐made shoes and
insoles, toe orthoses, etc.
Different therapeutic footwear designs can effectively offload at‐risk foot regions [35]. A
rocker‐bottom outsole configuration has been shown to be most effective, with up to 52%
pressure relief found [55, 56]. Custom made insoles have been shown to be effective in
relieving peak pressure compared to standard flat insoles [57]. Recent data have provided
confirmation for the efficacy of insole construction elements such as metatarsal pads and
bars and medial arch supports in offloading the forefoot [58, 59]. Additionally, new in‐vivo
evidence has been found for the efficacy of open and closed cell foam materials as top layer
for relieving pressure under the entire foot, and for removing and softening insole materi-
als at at‐risk regions [59]. However, the design and placement of metatarsal bars, pads, and
medial arch supports is critical: misplacement can lead to pressure increase in areas where
the foot needs offloading [60]. Plantar pressure measurement is a useful method to opti-
mize placement of these insole elements [61, 62].
The clinical goals of footwear for a diabetic patient are either to prevent the development
of an initial ulcer (in the case of primary prevention) [19] or to prevent a recurrence of
ulceration at the same site or new ulceration at a different site (in secondary prevention)
[5]. Most of the available evidence for the use of footwear in ulcer prevention is for the
prevention of ulcer recurrence [63, 64]. Several prospective studies had shown a beneficial
effect of the use of therapeutic footwear compared to standard footwear in preventing ulcer
recurrence and one RCT showed no effect [35]. These contrasting results were attributed to
the wide diversity of intervention and control conditions tested and the lack of information
about offloading efficacy of the footwear used, complicating the comparison of studies in
this area [40].
 7.7 ­Summar 133

Two more recently published multicentre RCTs have greatly improved our understanding
of the role of offloading in therapeutic footwear in the prevention of ulcer recurrence [28,
65]. In one, in‐shoe plantar pressure analysis was used to guide modifications to custom‐
made footwear that was delivered to patients based on the expertise of the clinical team.
Whilst this footwear could be significantly improved for its pressure‐relieving properties, it
showed a non‐significant 11% reduction in incidence of ulcer recurrence compared to cus-
tom‐made footwear that did not undergo such improvement in pressure [65]. However, in a
subgroup of patient who with objective measures were shown to be adherent to wearing
their prescribed footwear, the group with pressure‐improved footwear showed a significant
46% lower rate of plantar foot ulcer recurrence. In the other trial, the use of custom‐made
insoles that were designed and manufactured using barefoot plantar pressure and 3D foot
shape data and were worn in extra‐depth shoes led to a 63% reduction in recurrence of plan-
tar metatarsal head ulcers compared to the use of standard‐of‐care 3D foot shape based
custom‐made insoles [28]. These trials demonstrate that it is the combination of adequate
pressure relief and adherence to wearing the footwear that gives the best clinical effect.
What adequate pressure relief inside the patient’s shoe means in quantitative measures is
not exactly known, but we have some useful indications. One study examining patients who
had remained healed after plantar ulceration found a mean pressure of approximately
200 kPa at the prior ulcer site [66]. Data from the above‐mentioned trial showed that peak
pressures >200 kPa could be effectively reduced, but when pressure were <200 kPa, further
adaptation of the footwear proved futile [62]. A risk factor analysis of pressure‐related plantar
ulcer recurrence of the same trial showed that when peak pressure is <200 kPa and adher-
ence >80% risk of ulcer recurrence is only 0.4 compared to when these conditions are not met
[4]. Whilst an in‐shoe pressure threshold for foot ulceration is likely unique to each individ-
ual, as is the case with barefoot pressure, we now have indications that the 200 kPa value can
serve as a useful target in clinical practice for plantar offloading for prevention purposes.
Surgical interventions may reduce ulcer recurrence rates in selected patients when com-
pared to non‐surgical treatment because they permanently change the biomechanical envi-
ronment and reduce pressures at at‐risk and previously ulcerated regions [35]. Actually,
these procedures seem to be more effective in prevention than in the healing of foot ulcers
for which they are primarily chosen. However, complications with these procedures such
as transfer ulcers and impaired balance during walking may occur. Overall, the evidence
base to support the safe use of surgical procedures for ulcer prevention is still weak and
only a limited number of studies have emerged over the last few years [35]. Amongst the
surgical procedures, flexor tendon tenotomy – as discussed already for ulcer healing – seems
a promising and safe technique to prevent apex ulcers on the toes, but confirmation through
well‐conducted controlled studies is required.

7.7 ­Summary

This brief overview has presented a number of biomechanical issues which have direct relevance
to the development and treatment of foot complications in patients with diabetes. An under-
standing of the role that mechanical stress plays in tissue damage and healing of foot ulcers can
lead to better treatment and to more successful primary and secondary prevention of foot ulcers.
134 7 Biomechanics of the Diabetic Foot for the Uninitiated

­Acknowledgement

We gratefully acknowledge the contribution to this chapter of our colleague and mentor
Peter Cavanagh, PhD, DSc, who was a co‐author of this chapter in the previous editions.

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 139

Psychological and Behavioural Aspects of Diabetic Foot

Ulceration
Loretta Vileikyte1,2,3 and Ryan T. Crews4
1
Dept of Medicine, University of Manchester, Manchester, UK
2
Division of Endocrinology, Diabetes & Metabolism, University of Miami, Miami, FL, USA
3
Dept of Dermatology, University of Miami, Miami, FL, USA
4
William M. Scholl College of Podiatric Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

This chapter is an update of that published in the last edition of ‘The Foot in Diabetes’. In
addition to the role of psychological and behavioural factors in diabetic foot ulcer (DFU)
development, the current chapter discusses findings from the most recent application of psy-
chosocial research to this field, that is, the impact of depression on DFU healing. It demon-
strates that whilst depression is an important risk factor for incident first DFUs, the findings
linking depression to DFU healing remain inconclusive. Intriguingly, although DFU‐specific
cognitions and emotions influence preventive foot self‐care, it is depression that is signifi-
cantly associated with the development of the first DFUs, the link that does not appear to be
accounted for by poor foot self‐care. Thus, the pathways linking depression to an increased
DFU risk are yet to be established. The chapter emphasizes the importance of diabetic neu-
ropathy (DN)‐related unsteadiness both as a key factor in generating depression in patients at
high DFU risk and as an important determinant of non‐adherence to offloading in those with
active DFUs. Furthermore, it examines the interplay between the psychological and biome-
chanical factors when considering high DFU risk patients’ engagement in physical activity.
Finally, the chapter demonstrates that diabetic foot complications, and in particular, Charcot
Neuroarthropathy (CN), are associated with lower health status, especially in the physical
domain. Moreover, diabetic foot ulceration is a source of DFU‐specific emotional disturbance
and diminished quality of life (QoL). The chapter concludes with a discussion of the evidence
base for the best approach to study QoL in DFU sufferers.

8.1 ­The Role of Psychological and Behavioural Factors

in DFU Development

A recently updated systematic review of randomized controlled trials (RCTs) that evalu-
ated the role of patient education for DFU prevention reaffirmed previous conclusion
that, due to poor methodological quality of the existing studies, the available evidence

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
140 8 Psychological and Behavioural Aspects of Diabetic Foot Ulceration

respecting the efficacy of such interventions remains unconvincing [1]. Most studies were
underpowered, had insufficient follow‐up for outcome assessment, or failed to adequately
evaluate outcomes. Based on the only two sufficiently powered studies reporting the
effect of patient education on primary end points [2, 3] the authors concluded that there
is insufficient robust evidence that limited patient education alone is effective in achiev-
ing clinically relevant reductions in ulcer and amputation incidence.

8.1.1 Depression and Incident DFUs

Accumulating evidence suggests that psycho‐educational interventions may be most ben-
eficial for those high‐risk patients who have not yet experienced DFUs. A large epidemio-
logical study has showed that depression is associated with DFU incidence in a sample of
nearly 5000 type 2 diabetes patients without previous DFU or amputation [4]. This study
has shown that major depression assessed by Patient Health Questionnaire‐9 had a twofold
increase in the risk of incident DFUs. There was no statistically significant association
between minor depression and incident DFUs. These observations were further solidified
by an epidemiologic investigation demonstrating a link between symptoms of depression
and an increased DFU risk in a dose response manner during an 11‐year follow‐up [5].
Similarly, another prospective study of well‐defined DN population showed that both foot
self‐care and depression, whilst having no impact on the development of recurrent DFUs,
play a substantial role in incident foot ulceration in high‐risk patients with no prior DFUs
[6]. In patients with no prior DFUs, each one standard deviation increase in depression
symptoms was significantly associated with increased risk of developing first foot ulcers
(HR = 1.68, 95%CI: 1.20, 2.35) whilst foot self‐care was associated with lower risk
(HR = 0.61, 95%CI: 0.40, 0.94). The fact that depression, like foot self‐care, was associated
with DFU risk only in those without a prior DFUs suggests that the effects of these psycho-
logical and behavioural factors may not be robust enough to come into play in the context
of very high levels of risk. Thus, addressing the psychological and behavioural factors in
those patients with previous DFU may be ‘too little, too late’.

8.1.2 DFU-Specific Emotional Distress Versus Depression

in Shaping Foot Self-Care
Somewhat unexpectedly, depression, whilst predictive of DFU incidence, was not associ-
ated with poor adherence to foot self‐care in these reports. This challenges the assumption
that non‐adherence to foot self‐care is the mechanism linking depression to DFU inci-
dence. The finding is consistent with the meta‐analytic review of the studies that examined
the relationship between depression and a variety of diabetes self‐care behaviours [7]. The
effect of depression on self‐care varied across different types of self‐care behaviours in this
meta‐analysis, with the strongest effect size found for missed medical appointments and
the smallest effect size found for foot self‐care, which was non‐significant. In fact, we found
that higher depression scores were associated with greater frequency of foot self‐care,
which in turn was associated with lower DFU risk in multivariate analysis [6]. Adding
behaviour to the multivariate model increased rather than reduced the strength of the
unique association between depression and DFU risk. Whilst at first glance these results
 8.1 ­The Role of Psychological and Behavioural Factors in DFU Developmen 141

may appear paradoxical, we believe they suggest that the association between depression
and DFU may involve at least two countervailing components. First, patients engaging in
more frequent foot self‐care may have been more aware of their heightened health risk and
thus more likely to experience symptoms of depression. Whilst in this way depression was
associated with lower DFU risk through its relationship with more frequent foot self‐care,
depression also was associated with higher DFU risk through pathways that were not iden-
tified by our analyses. Whether depression represents an indicator of biological risk that
was not captured by the risk factors measured in the current study or whether it truly is a
causal agent, acting via mechanisms other than foot self‐care, in the development of foot
ulcers, is an important question that deserves further investigation. It is also possible that
current measures of foot self‐care do not capture the full impact of foot self‐care on the
DFU risk, so that a more comprehensive measure might more fully mediate the relation-
ship between depression and foot ulceration.
Whilst the relationship between depression and foot self‐care requires further clarifica-
tion, growing body of evidence indicates that illness‐specific emotional responses are more
important predictors of self‐care behaviours than the measures of generalized distress [8].
In the context of diabetic foot complications, we demonstrated [9] that anger at practition-
ers stemming from a perceived lack of compassion hinders foot self‐care, whilst the most
prominent emotion in those at high DFU risk – worry about an amputation [10] – pro-
motes foot self‐care actions. Moreover, we have shown that although patients at high‐risk
for DFU experience elevated depression symptoms, these are largely determined by DN‐
related physical dysfunction and interpersonal‐emotional burden [11, 12]. These findings
are congruent with a growing body of research demonstrating that self‐reported depressive
symptom measures are more reflective of diabetes‐specific distress than of clinical depres-
sion [8]. Addressing causes of illness‐specific emotional reactions may, therefore, be more
meaningful and effective than initiating treatments specifically directed at clinical
depression.

8.1.3 Patient Cognitive Representations of DFU Risk

and Preventive Foot Self-Care
An important limitation of the earlier DFU educational trials is their exclusive focus on foot
self‐care knowledge and behavioural skills training: none of these studies addressed poten-
tial psychological factors underlying patients’ foot self‐care actions. The Common Sense
Model (CSM) of illness behaviour provides a framework for exploring how people give
meaning and make decisions to take specific actions in response to the diagnosis and symp-
toms associated with chronic illness [13]. The CSM postulates that patients process health‐
threatening information by constructing common sense disease models or understanding
about illness in terms of symptoms and diagnostic labels, antecedent conditions believed to
cause illness, expected duration, possibility of cure or prevention and anticipated impact of
illness. Two types of information are integrated when patients construct ‘common sense’
views of their health status: verbal information from other persons, including physicians,
other patients and family members, and concrete experience of symptoms and physical
dysfunction. In the context of DFU risk, it is therefore important to determine whether the
patients’ understanding of their foot ulcer risk is sufficient for his/her participation in foot
142 8 Psychological and Behavioural Aspects of Diabetic Foot Ulceration

self‐care. Thus, uncovering the patients’ representations of diabetic foot complications and
understanding how patients merge lay beliefs with information from practitioners may
hold the key to understanding patients’ participation in foot self‐care.
The combination of the CSM with clinical experience and evidence from interviews with
patients at high risk for foot ulceration has informed the development of the Patient
Interpretation of Neuropathy (PIN) questionnaire, an instrument for the assessment of
cognitive and emotional factors associated with foot self‐care [9]. This 39‐item instrument
consists of nine scales capturing patients’ common‐sense misconceptions about DFU risks,
their level of understanding of practitioner information, and foot problem–specific emo-
tional responses. Using the PIN instrument and path modelling technique, we examined
the ways patient common‐sense models of DFU risks combine with medical information,
specific emotional responses and prior DFU in predicting stable foot self‐care behavioural
patterns over 18 months of follow‐up [14]. We demonstrated that patient misconceptions:
‘good circulation means healthy feet’ and ‘the development/worsening of DFU would be
accompanied by pain’, predicted potentially foot‐damaging behaviours. In contrast, accu-
rate interpretation of medical information about the nature of DFU risks and understand-
ing of the causal pathways linking DN to DFU predicted more preventive foot self‐care
both directly and indirectly, i.e. by correcting the patient misconceptions and altering emo-
tional reactions. Prior DFU also predicted better preventive foot self‐care and less poten-
tially foot‐damaging behaviours both directly and by correcting the patient misconceptions.
Subsequently, a cross‐sectional study of patients at high DFU risk employed the PIN and
hierarchical cluster analyses to identify distinct illness schemata related to neuropathy
[15]. The cluster of patients with high misperceptions of DN undertook more potentially
damaging foot‐care behaviours than those with generally realistic beliefs about the nature
of neuropathy as a DFU risk factor.
There is evidence that beliefs about treatment are at least as important as beliefs about
illness in predicting health‐related behaviours. An investigation of patients that had been
provided custom‐made footwear for preventing secondary DFU found that the perceived
benefit of the footwear was the only significant predictor of self‐reported adherence [16].
The same group had published data regarding objectively measured adherence to custom‐
made footwear for DFU prevention and found that in addition to lower BMI and more
severe foot deformity, the subjective perception of more appealing footwear was signifi-
cantly associated with better adherence to prescribed footwear [17].

8.2 ­The Role of Psychological and Behavioural Factors

in DFU Healing

8.2.1 The Impact of Depression on DFU Healing

Exploring the role of depression in DFU healing represents one the most recent applica-
tions of psychosocial research to this field, emerging from studies that examined the
relationship between psychological stress and the healing of acute wounds, both in
rodent models and human volunteers [18]. The first such study in DFU patients exam-
ined the role of geriatric depression in foot ulcer healing over a six‐month follow‐up
 8.2 ­The Role of Psychological and Behavioural Factors in DFU Healin 143

[19]. Healing was associated with a smaller DFU area at baseline, lower glycated hae-
moglobin and higher ankle‐brachial index. Both smoking status and DFU severity had
a significant negative impact on healing. Importantly, patients who healed had signifi-
cantly lower scores on the geriatric depression scale. A subsequent investigation [20]
considered the role of depression and coping styles in the healing of DFUs over a 24‐
week period. Additionally, explored were salivary cortisol and matrix metalloprotein-
ases (MMPs) as potential mechanisms linking depression to DFU healing. After
controlling for clinical and demographic determinants of healing, ulcer healing at
24 weeks (primary outcome) was predicted by confrontation coping, but not by depres-
sion or anxiety. However, change in ulcer size over the observation period (secondary
outcome) was associated with depression only. Furthermore, healed ulcers by 24 weeks
were associated with lower evening cortisol, lower precursor MMP2 and a greater corti-
sol awakening response. Whilst an interesting undertaking, this report has several
methodological issues [21]. The presented data provided no mechanistic evidence, but
merely demonstrated that indicators of cortisol and MMPs are associated with ulcer
healing. It is not reported whether these potential mediators were associated with the
predictors in question (i.e. depression and confrontational coping), or whether control-
ling for the purported mechanisms attenuated the relationship between the predictors
and outcome. Restricting their analyses to those with complete data on these variables
would also have addressed the possibility that the reported differences in the associa-
tions between depression, confrontational coping, and healing outcomes may have been
due to chance variations in the relationships between these variables across quite differ-
ent samples. A recently conducted small scale study [22] examined the effects of physi-
ological stress on DFU healing speed defined as percentage change in wound size
between the two consecutive visits. Whilst there was a moderate but significant correla-
tion between depression scores and physiological stress/vagal tone, an association
between depression and DFU healing was not observed. In contrast, lower heart rate
variability (a proposed indicator of physiological stress response) showed a significant
correlation with slower DFU healing. The authors therefore concluded that subjective
stress assessments may not capture adequately the level of physiological stress, and that
it is the physiological and not psychological stress that delays the healing of DFUs.
However, the study population does not appear to be sufficiently clinically defined. For
instance, the subjects in this report might have had cardiac autonomic neuropathy in
which case the heart rate variability may not have been the best measure of physiologi-
cal stress response. As a result, definitive conclusions regarding the role of depression
in DFU healing cannot not be drawn from these reports.

8.2.2 Determinants of Adherence to Offloading in DFU Healing

Although clinical opinion suggests the importance of adherence to off‐loading in DFU
healing, only recently has the relationship between objectively measured offloading adher-
ence (OA) and DFU healing has been confirmed [23]. The results of this prospective study
provide evidence for a relationship between varying levels of off‐loading adherence and the
amount of DFU healing that occurred during a six‐week period. The results supported the
hypothesized role of DN‐related symptoms as determinants of adherence to off‐loading.
144 8 Psychological and Behavioural Aspects of Diabetic Foot Ulceration

Specifically, DN‐related unsteadiness emerged as a symptom most strongly associated with

poorer off‐loading adherence. The other predictors of off‐loading adherence were physical
(more severe neuropathy, larger and more severe DFU and more severe perceived foot
pain). Patients with these characteristics adhered more consistently to off‐loading, presum-
ably because they were more motivated by the greater diagnosed and experienced severity
of their medical condition. Interestingly, there were no significant associations of adher-
ence to off‐loading neither with depression nor with DFU‐specific beliefs and emotional
responses. This challenges the relevance of findings by Vedhara et al. [24] regarding the
importance of DFU‐specific beliefs in predicting foot self‐care in those with active DFUs.
Whilst the foot self‐care behaviours included in their report (e.g. checking of feet or inspect-
ing inside of shoes) may well be helpful in DFU prevention, they have little benefit in those
with active DFU, where adherence to off‐loading rather than preventive foot care is central
to the healing of foot ulcers. Perhaps beliefs that are more closely focused on an offloading
device, such as expected efficacy or convenience might be more powerful predictors than
patient perceptions of their DFU.
Whilst a few publications have focused upon the effect of offloading devices upon the
users’ stability, to date there has been a lack of studies investigating ways of improving
OA [25]. Most studies evaluating offloading devices focus on the devices’ functional
capacity to offload wounds. However, they rarely seek to improve the patient experience.
One study that focused on design considerations that could improve the patient experi-
ence found that a reduction in cast walker height (and subsequently weight) did not
substantially reduce offloading functionality [26]. However, the reduction in walker
height did yield some trends of improved gait parameters. Taking such a patient centred
approach to prescribing and designing offloading devices may result in improved patient
adherence.

8.2.3 Predictors of Depression in Patients at High DFU Risk

The emergence of DN‐unsteadiness as the symptom that is most strongly associated with
nonadherence to offloading [23] merits attention, especially, as studies indicate that DN‐
unsteadiness is an important determinant of depression in patients at high risk for develop-
ing DFUs [11, 12]. A cross‐sectional study showed that self‐reported neuropathic pain,
unsteadiness, and reduced feeling in the feet were each independently associated with
depression and together accounted for the relationship between the clinical measures of
DN severity and depression. Furthermore, the association between DN symptoms and
depression was partially mediated by two sets of psychosocial factors: (i) restrictions in
activities of daily living and diminished self‐worth, and (ii) illness cognition, or the percep-
tions of neuropathic pain unpredictability and the lack of treatment control [11]. The lon-
gitudinal findings were largely consistent with the cross‐sectional observations and
demonstrated that more severe DN at baseline is associated with worsening depressive
symptoms over 18 months of follow‐up [12]. Whilst neuropathic pain contributed to depres-
sion, unsteadiness and its psychosocial consequences dominated this relationship over
time. Unfortunately, balance deficits may be overlooked by clinicians, as patients often do
not report balance concerns during medical consultations owing to the perception that
these are an indicator of diminishing self‐resources – a sign of premature ageing rather
 8.2 ­The Role of Psychological and Behavioural Factors in DFU Healin 145

than illness‐related disability [27]. A recent study [28] demonstrated that perceptions of
unsteadiness reported prior to laboratory tests correlated with objective measures of bal-
ance impairment during walking. Moreover, DN patients were not only aware of them-
selves as being unsteady but actually attempted to self‐regulate their unsteadiness by
altering specific gait parameters. As a result of feeling unsteady, patients with diabetic
peripheral neuropathy adjusted their gait by walking more slowly and taking shorter steps.
Whilst these ‘self‐initiated’ strategies are likely to be beneficial to a certain extent, they
seem to be insufficient for effective balance control. Considering the above discussion, cli-
nicians should take this neuropathic symptom into consideration when selecting an off‐
loading device, as off‐loading–induced postural instability may further contribute to
nonadherence. The patient’s perception of their unsteadiness appears to be an adequate
indicator of the actual balance impairment [28].
Somewhat unexpectedly, neither prior nor active DFUs were independently associ-
ated with depression in the reports that examined the association between Distal
Sensory Peripheral Neuropathy (DSPN) and depression [11, 12]. This observation was
corroborated by a large epidemiologic cross‐sectional investigation from Norway [29].
Amongst people with diabetes, a history of foot ulcer whilst having a significant nega-
tive impact on perceived health did not independently contributed to depression scores.
Nonetheless, even though DFUs are not independently associated with depression, they
serve as a marker for an increased risk for elevated depressive symptoms. Therefore,
DFU patients should be carefully monitored to determine whether they are depressed,
especially in the light of findings linking depression to an increased mortality in this
patient population [30].

8.2.4 Physical Activity and DFU Healing

Management of physical activity in patients with active DFUs is poorly understood. There
is evidence that physical exercise accelerates wound healing in rodents and humans [31]
although the mechanisms are not clear. Najafi et al. [32] investigated patterns of physical
activity and their relationship to wound healing in patients with DFUs protected with
either a removable cast walker (RCW) or irremovable instant total contact cast. Irrespective
of offloading modality, there was an inverse association between rate of weekly wound
healing and number of steps taken per day. However, as noted by the authors, the study did
not control for OA in the RCW group. It remains therefore unclear whether the relation-
ship between physical activity and healing varied as a function of OA. The results of a sec-
ondary analysis of an international UK/US study of subjects with plantar DFUs suggest
that offloading‐adherent weight‐bearing physical activity has no independent effect on
healing [33]. Interestingly, amongst the potential demographic, disease, and psychological
determinants of physical activity, only depression was significantly independently associ-
ated with lower step count. Depression should therefore be targeted as part of comprehen-
sive DFU management, especially in light of findings linking depression to DN‐unsteadiness – a
key predictor of nonadherence to offloading and, in turn, impaired foot ulcer healing.
These observations are a perfect example of how psychological (depression) and biome-
chanical (unsteadiness and offloading) factors interrelate in shaping patient self‐manage-
ment of active DFUs.
146 8 Psychological and Behavioural Aspects of Diabetic Foot Ulceration

8.3 ­The Impact of DFUs on Patients’ Health Status and QoL

Studies have demonstrated that DFUs have a major negative impact on patients’ health
status and QoL. The loss of mobility caused by non‐weight‐bearing treatment is central to
foot ulcer experience [34]. Limited mobility results in severe restrictions in activities of
daily living, including daily tasks, leisure activities, and employment. Brod, for example,
reported that approximately half of the interviewed patients had either retired early or lost
time from work, and career opportunities were sometimes missed [35]. Moreover, DFUs
cause problems with social and interpersonal relationships and the perceptions of dimin-
ished value of the self as a consequence of inability to perform social and family roles [27].
Quantitative studies confirmed the findings of qualitative research that DFUs exert a
negative effect on physical functioning, psychological status, and social situation. Using a
generic measure of health status, the EQ‐5D, researchers from Sweden demonstrated that
subjects with current DFUs had lower health status than both patients who had healed
primarily without any amputation and those who had undergone a minor amputation [36].
A recent study by the Eurodiale group [37] extended these observations by showing that a
minor amputation does not negatively affect the patient’s reported health status as com-
pared with conservative treatment of DFUs. It was therefore suggested that minor amputa-
tion may not be considered treatment failure but rather a viable treatment option. Several
longitudinal studies of patients with DFUs demonstrated that poor health status, as meas-
ured with another widely used health status instrument, the generic Short Form (SF)‐36,
was associated with poor DFU prognosis [38, 39]. In these reports health status improved
significantly with healing of DFUs, and deteriorated in those patients whose DFUs recurred
or did not heal. An interesting report from Holland demonstrated that persistent foot ulcers
have a negative effect not only on DFU sufferers but also are a source of severe emotional
burden on their caregivers [40].
The Eurodiale group has demonstrated that poor health status in DFU patients is deter-
mined by comorbidities, DFU size, peripheral vascular disease, and elevated C‐reactive
protein [41]. A report by Ribu et al. [42] corroborated these observations emphasizing the
strongest link with the SF‐36 physical functioning. Furthermore, Raspovic and colleagues
have demonstrated that the SF‐36 physical and not the mental component predicted major
amputations and mortality in patients with diabetic foot complications and end‐stage
renal disease [43]. Intriguingly, health status of these patients, especially in the physical
domain, whilst predictive of major amputation and mortality, was not predictive of DFU
healing [44].
Most recent publications conducted by Wukich et al. extended this area of enquiry to
patients with CN [45–47]. When comparing CN patients to those with diabetes and no CN,
there was no significant difference between the SF‐36 mental component summary scores.
However, the SF‐36 physical component summary scores in patients with CN were notably
lower than the scores in the control group [46]. Another study compared health status of
patients with midfoot CN and no ulcer and a group of diabetic patients with midfoot CN
and concurrent DFU. Both groups demonstrated negative impact on physical health status
and lower extremity function to a greater degree than on mental health status. The pres-
ence of ulceration did not appear to significantly impact QoL in patients with CN when
compared to patients with CN without ulceration [47].
 8.4 ­Measuring QoL in DFU Patients: Generic, DFU-Specific or Combined Approach 147

8.4 ­Measuring QoL in DFU Patients: Generic, DFU-Specific

or Combined Approach?

The aforementioned studies that employed generic measures of health status, such as the
EQ‐5D or the SF‐36, revealed a common pattern, that is, that DFUs affect health predomi-
nantly in the domain of physical functioning: the impact of DFUs on mental functioning
was nonsignificant in most of these reports. This observation is consistent with general
literature that reviewed the impact on QoL of other medical conditions, such as neuro-
pathic pain [48]. This review provided evidence that the condition‐specific QoL measures
are more sensitive to the effects of physical illness than the generic instruments of physical
and especially mental functioning. One of the possible explanations could be that generic
scales of mental functioning are only sensitive to the presence of severe mental problems,
such as clinical depression. Indeed, a recent study demonstrated that the SF36 has suffi-
cient specificity and sensitivity to categorize patients at risk for major depressive disorder
[49]. However, as diabetic foot ulceration is not independently associated with depression
[11, 12] it may therefore not impact significantly on mental functioning as measured by the
generic scales. Nonetheless, DFUs are a source of specific emotional distress, such as fear
of amputation [9, 10]. It is therefore plausible that generic measures of mental functioning
are not sensitive enough to DFU‐related emotional disturbance. A study that compared the
performance of the generic SF‐12 and a neuropathy and foot‐ulcer‐specific questionnaire,
the Neuropathy and Foot‐Ulcer‐Specific Quality of Life instrument (NeuroQoL) demon-
strated that whilst the mental functioning scale from the SF‐12 was not associated with
DFU presence, a foot‐problem‐specific emotional burden scale from the NeuroQoL showed
a strong association with the presence of foot ulceration and was the most important link
between foot ulceration and reduced QoL [27]. Taken together, it would seem appropriate
to supplement the generic tools of health status with validated condition‐specific question-
naires when studying the impact of DFUs on health status and QoL, especially, in the emo-
tion domain. Examples of such questionnaires include the Diabetic Foot Ulcer Scale (DFS)
[34] and the NeuroQoL [27]. A recent systematic review of the value of various instruments
in assessing QoL in patients with diabetes‐related foot disease demonstrated that DFU‐spe-
cific tools were better than generic measures at quantifying temporal changes in life quality
and showed greater sensitivity to DFU severity [50]. It was therefore suggested that DFU‐
specific surveys may improve the evaluation of QoL as a function of ulcer healing, the
effect of different treatment methods on QoL, and the relationship between DFU‐specific
QoL, patient adherence, and treatment efficacy.
In summary, diabetic foot ulceration is a source of severe physical dysfunction, emo-
tional distress and poor QoL. DFU‐specific scales capture more adequately than generic
measures the impact of foot ulceration on an individual’s functioning, especially in the
emotional domain. Whilst foot ulceration is not predictive of depressive symptoms, it is a
source of ulcer‐specific emotional responses, which either facilitate (fear of potential con-
sequences) or inhibit (anger at health care providers) preventive foot self‐care actions.
Patients respond to diabetic foot complications by creating their own models or under-
standing about this medical disorder, which is largely inconsistent with the practitioner’s
view, resulting in a lack of foot self‐care. Although DFU‐specific cognitions and emotions
influence preventive foot self‐care, it is depression that is associated with an increased risk
148 8 Psychological and Behavioural Aspects of Diabetic Foot Ulceration

for DFU, the link that does not appear to be accounted for by poor foot self‐care. Thus, the
pathways linking depression to an increased DFU risk are yet to be established. Neuropathic
unsteadiness is the symptom with the strongest, cumulative effect on depression. Moreover,
unsteadiness is the key determinant of nonadherence to offloading in active DFU patients.
Clinicians should therefore address unsteadiness when assessing patients with at high
DFU risk, especially as the patients’ perception of their unsteadiness appears to be an ade-
quate indicator of the actual balance impairment. Whilst research indicates that depres-
sion is an important risk factor for incident first DFUs, the findings linking depression to
DFU healing remain inconclusive. Finally, our understanding of the management of physi-
cal activity in high DFU risk patients is still in its infancy, although body of evidence indi-
cates that supervised weight‐bearing exercise interventions are beneficial and do not
increase the DFU risk.

­Acknowledgement

I thank the Diabetes UK (RD00/0002009) and NIH (NIDDK R01‐DK‐071066) for their gen-
erous support of some of the studies reported in this review.

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 153

What Role for the Plain Radiograph of the Diabetic Foot?

Richard William Whitehouse
Manchester Royal Infirmary, Manchester University Hospitals Foundation NHS Trust, Manchester, UK

9.1 ­Introduction

Radiography of the foot is used for diagnosis. The accuracy of the diagnosis made from a
radiograph is influenced by technical factors (the quality of the radiographs, appropriate-
ness of the imaging projections requested and performed), the interpretative skill of the
observer, knowledge of the clinical findings (which may be extensive if the observer is the
managing physician, or limited to the information on the request for the radiologist) and
knowledge of the results of other tests, including previous radiographs. It should therefore
be appreciated that a radiological diagnosis may be subject to review and revision. Indeed,
review should be requested if there is disparity between the report and clinical suspicion.
In patients with diabetes and foot complications, the above observations remain perti-
nent and plain radiography should be the usual initial radiological investigation. The
pathologies that might be suspected in a diabetic foot; fracture, Charcot’s neuroarthropa-
thy, ulceration with or without osteomyelitis, can all be demonstrated on plain radiography
albeit with varying sensitivity and specificity. Where such a diagnosis is confirmed by a
radiograph and fits the clinical circumstances then further investigation and management
can be tailored as appropriate.
There is a legal requirement for all medical exposures to ionizing radiation to be justified.
In the United Kingdom this legislation is embodied in the Ionizing Radiation (Medical
Exposures) Regulations – IR(ME)R. The justification is to be provided by the person
requesting the examination, and based on their knowledge of the risks of radiation and
benefit of the examination. The justification has to be accepted by the person performing
the examination, who can then authorize and perform it. The typical effective radiation
dose from foot radiography is less than 5 microSieverts (μSv), whilst the background radia-
tion in the UK averages 2.4 mSv per annum. The effective radiation dose from foot radiog-
raphy is thus less than the background radiation received in a single day from living in the
UK. The radiation risk from foot radiography against which to balance the benefits of the
examination should therefore be considered to be negligible. MR uses no ionizing radia-
tion, but PET, other nuclear medicine studies and CT scans can give radiation doses 2–3

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
154 9 What Role for the Plain Radiograph of the Diabetic Foot?

orders of magnitude higher than plain radiographs, as well as being considerably more
expensive and less widely available.
There have been technical advances in plain radiography over the last decades, from
film/screen, through computerized radiography (CR), where the radiograph is acquired
on an imaging plate that is then read by a laser scanner, to the development of digital
imaging plates that provide direct acquisition of the radiographic image into electronic
systems‐direct digital radiography (DDR). CR and DDR have wider latitudes than conven-
tional film radiography, which can compensate for exposure errors. Being digital images,
CR and DDR images can be electronically processed and manipulated on a workstation.
DDR is of higher resolution than CR, even more radiation dose efficient and does not have
the intermediate step of reading the CR image plate. Many of the limitations of conven-
tional radiography do, however, remain. Limited soft tissue contrast resolution, superim-
position of complex structures and adequate evaluation of cortical bone being restricted to
those bone edges depicted in profile are the main limitations of radiography. In addition,
visible changes on radiographs tend to lag behind the evolution of disease by up to three
weeks, both in its progression and its resolution. The image processing that ‘brings out’
soft tissue appearances in the image also reduce the contrast of bony structures, conse-
quently the assessment of bone density, for example (already subjective on conventional
films) is even more difficult.
Despite these advances, no recent improvement in sensitivity or specificity of plain radi-
ographs for diabetic foot pathologies is well documented in the literature. Technical
advances in other imaging techniques; computed tomography, Magnetic resonance imag-
ing, Positron emission tomography, labelled leucocyte isotope scans and other nuclear
medicine scans, with fusion imaging combining PET and other isotope scans with CT or
MR scans have also occurred, along with increasing availability of these imaging tech-
niques. Local availability and expertise may predicate imaging pathways for diabetic foot
assessment. However, with care and attention to technique and interpretation, the plain
radiograph can remain the initial radiological diagnostic test for diabetic foot complica-
tions. Despite this, even hospital admission for infected diabetic foot ulceration may not
precipitate a radiographic examination, with 33% of such patients not being radiographed
in one study [1], a figure unlikely to have improved over the recent years.

9.1.1 Image Resolution

Image resolution in radiographs can be measured in line pairs per millimetre (lp/mm),
with conventional film providing resolutions between 2 and 10 lp/mm. The higher resolu-
tion films were typically used for mammography and dental radiography, with ‘detail’ films
also available for selected peripheral radiographs (e.g. hand films for assessment of erosive
arthritis). Computerized radiography plates for general radiographic applications have
lower spatial resolution, generally up to 3.5 lp/mm, but standard DDR plates are of higher
resolution than CR (Figure 9.1.), whilst specialized DDR plates for dental radiography have
effective spatial resolution of 10–20 lp/mm. These small plates can be placed between the
toes, providing lateral radiographs of a toe without overlap by the adjacent toes beyond the
plate and at very high resolution. If available, we advocate the use of ‘dental’ imaging plates
for toe radiography in diabetic feet (Figure 9.2).
 9.1 ­Introductio 155

(a) (b)

Figure 9.1 (a) CR radiograph performed at presentation with an apical soft tissue ulcer. Follow-up
radiograph (b) performed on DDR shows higher resolution with sharper bone definition, making
assessment of serial change in bone appearances more difficult. Serial examinations should be
performed on the same imaging system whenever possible.

(a) (b)

Figure 9.2 Comparison of (a) The second and third toes on a routine oblique foot radiograph and
(b) a true lateral radiograph acquired on a dental plate. Note sites of cortical erosion by
osteomyelitis (arrowheads).
156 9 What Role for the Plain Radiograph of the Diabetic Foot?

9.1.2 Radiographic Projections

Radiographic projections are the ‘views’ that can be taken, performed to standardized cri-
teria. Projections are described by the direction taken by the x‐ray beam as it travels through
the patient. Routine projections for the foot are dorsi‐plantar (DP) and oblique, the latter
view giving a clearer demonstration of the midfoot articulations. Less commonly per-
formed routinely is a lateral view. Routine projections for the ankle are antero‐posterior
(AP) and lateral. Important additional views in the diabetic foot are calcaneal views – lat-
eral and axial, sub‐talar joint views, lateral toe views, the sesamoid view (Figure 9.3) and
tangential radiographs. The request for radiographs should therefore include details of the
site of ulceration, if present, and a request for appropriate additional and/or tangential
views of the region of ulceration.

9.1.3 Patient Preparation

Patients with diabetic foot ulceration may have a variety of dressings over their wounds.
There may be medications applied topically or implanted into ulcers. They may have fixed
or removable casts or splints in place. Radiographers will not usually have the training or
inclination to remove and subsequently replace casts or dressings and will consequently
radiograph the patient through these items. Casts and splints may create difficulty in posi-
tioning the limb for a radiograph, resulting in suboptimal projections, whilst all the items
will create artefacts in the radiograph, which may obscure detail. Ideally therefore, all casts,
splints, and dressings should be removed before the patient is sent to radiology, and
replaced when they return.

9.1.4 Serial Radiography

Fractures, Charcot neuroarthropathy (CN) and osteomyelitis in the diabetic foot almost
invariably show radiographic abnormality eventually, even if initially occult. The relatively
poor sensitivity and specificity of plain radiographs for osteomyelitis in particular relates to
the initial acute presentation, but the value of serial radiographs at 10–14 day intervals is

Figure 9.3 Sesamoid view, demonstrating the sesamoid bones beneath the great toe metatarsal
head.
 9.2 ­Pathologie 157

not described in the literature. A recent review suggested that changes in radiographic
appearances over a period of time may therefore be more useful than a single study [2], an
opinion with which we concur. Initially occult fractures and acute CN may also be identi-
fied on serial radiographs before excessive irreversible deformity has developed.

9.2 ­Pathologies
9.2.1 Vasculopathy
Peripheral vascular disease is common in diabetes. In the foot and ankle relative sparing of
the dorsalis pedis but involvement of the posterior tibial and peroneal arteries is often seen.
On plain radiographs small vessel calcification can be seen throughout the foot (Figure 9.4.).
Proper assessment of the vascular supply requires angiography, though contrast enhanced
MR or CT is replacing conventional catheter angiography for this. The presence of
­radiographically demonstrated medial arterial calcinosis in diabetic feet is associated with
neuropathy, ulceration, amputation, and excess mortality [3]. Dry gangrene results in
shrinkage of the affected soft tissue and linear subcutaneous gas collections may also be
present, but the underlying bone usually appears radiographically normal.

Figure 9.4 Extensive vascular calcification in the foot. There is also a soft tissue ulcer crater and
underlying osteomyelitis in the great toe.
158 9 What Role for the Plain Radiograph of the Diabetic Foot?

9.2.2 Fracture
Plain radiography is fundamental to the diagnosis and management of fracture and dislo-
cation in the foot and ankle. Recent fractures and dislocations, bone deformities from
healed previous fractures and progressing neuropathic fracture/dislocations will all be
demonstrated on radiographs. Although foot deformity will be clinically apparent, the radi-
ographs can draw attention to underlying bone deformities that may predispose to soft tis-
sue ulceration by forming pressure points. Metallic or glass radio‐opaque foreign bodies
may be identified in the foot and may predispose to infection. Bone regrowth after surgical
partial resection of metatarsal bone may also form pressure points and predispose to ulcer-
ation (Figure 9.5). Plain film demonstration of regrowth exceeding 3 mm was demonstrated
in 45% of such patients between one and three years after surgery [4]. Evidence of trau-
matic fractures, often previously unrecognized, in neuropathic diabetic feet is common,
being found in 22% of neuropathic diabetic feet in one study [5].
Bone density is generally decreased in type I diabetes but increased in type II diabetes,
compared with controls, but in both types there is decreased bone strength and increased
fragility fracture risk. An increased prevalence of pedal fracture has been identified in
­diabetic athletes, particularly fifth metatarsal fractures. In our practise, Jones fractures of
the fifth metatarsal (Figure 9.6) and sagittal fractures of the navicular bone (Figure 9.7) in
diabetic patients with no athletic activity have been increasingly identified. These fractures
in non‐diabetics are often stress fractures in active or athletic individuals – we suggest neu-
ropathy and consequent unrestrained continued activity, even at a relatively low level, may
contribute to a stress type aetiology of these fractures in diabetics. These fractures have
been slow to heal and in the case of the navicular fractures, have been prone to fragmenta-
tion and collapse of the lateral part of the navicular. Another unusual fracture that is
described in diabetic patients is the open beak fracture of the calcaneum, and although
attributed to neuropathy, heel ulceration and underlying osteomyelitis appear to ­predispose

Figure 9.5 Lateral view of the foot demonstrates a bone spike projecting from the amputation
stump of the great toe metatarsal, this may predispose to ulceration.
 9.2 ­Pathologie 159

Figure 9.6 Jones fracture of the fifth metatarsal.

Figure 9.7 Navicular fracture.

160 9 What Role for the Plain Radiograph of the Diabetic Foot?

Figure 9.8 ‘Open beak’ fracture of the calcaneum.

to this fracture, probably through weakening of the posterior calcaneum and overlying
fascia, which transmit tensile forces from the Achilles tendon to the plantar fascia
(Figure 9.8).
Recognition of foot fractures in patients with diabetes and adequate protection of frac-
tures until they have firmly united is recommended as progression to CN joint changes is
commoner when there is delayed diagnosis and treatment of foot fractures [6].

9.2.3 Osteomyelitis and Soft Tissue Infection

Radiographic features suggesting osteomyelitis are bone destruction or demineralization,
bone sclerosis, periosteal reaction, and the presence of gas or an ulcer in the adjacent soft
tissues. In the small irregular bones of the foot, periosteal reaction is not commonly seen,
but may occur around the shafts of the metatarsals. The commonest initial radiographic
feature of acute osteomyelitis is focal bone demineralization. This may progress to frank
bone destruction, whilst denser devitalized bone remnants within the region of osteomyeli-
tis form sequestra in chronic osteomyelitis. Successful antibiotic treatment can reverse the
demineralization of acute osteomyelitis, the affected bone then radiographically re‐appears
(Figure 9.9). Sequestra may spontaneously extrude through sinus tracks or be removed
through the adjacent ulcer during debridement (consequently disappearing on subsequent
radiographs) and antibiotic impregnated calcium sulphate pellets may be inserted produc-
ing a foreign body on radiographs (Figure 9.10).
Osteomyelitis in the diabetic foot usually develops in the bone adjacent to the floor of a
soft tissue ulcer. The ulcer may probe to the bone surface and if it does so, the probability
(a) (b) (c)

Figure 9.9 (a) Initially unremarkable radiographic bony appearances to the second toe, which was
swollen with apical ulceration. This progressed to frank osteomyelitis (b) with marked soft tissue
swelling, demineralization of the terminal and middle phalanges with pathological fracture of the
middle phalanx. On successful treatment with antibiotics (c) the apparently destroyed terminal
phalanx re-mineralized.

(a) (b)

Figure 9.10 Antibiotic pellets, (a) when recently implanted; (b) smaller and irregular in
appearance when partially absorbed.
162 9 What Role for the Plain Radiograph of the Diabetic Foot?

Figure 9.11 Gas in the soft tissues beneath the calcaneum, with underlying bone destruction at
the base of the fifth metatarsal, indicating osteomyelitis. Note the vascular calcification.

of osteomyelitis being present is high. Consequently, although the sensitivity and speci-
ficity of plain radiography for the diagnosis of osteomyelitis is around 0.54 and 0.68
respectively [7], when combined with a clinical probe to bone test these rise to 0.97 and
0.92 [8]. The radiographic sensitivity and specificity is based on the initial radiograph.
Serial radiography may further increase the sensitivity and specificity where initially neg-
ative, and further serial radiographs can demonstrate response to treatment.
Soft tissue ulceration may contain gas, which may extend down to the bone surface or
even into an osteomyelitic cavity within the bone. Gas in the tissues may be in an ulcer cav-
ity, ‘pumped’ into the soft tissues by the pressure of walking on an ulcer cavity or due to soft
issue infection by a gas‐forming organism (Figure 9.11). In necrotising fasciitis of the lower
limb in diabetics, gas was seen in the soft tissues on plain radiographs in 44% of affected
patients [9].

9.2.4 Charcot Neuroarthropathy

Acute CN may be radiographically almost occult. There is, however, usually ‘non‐specific’
soft tissue swelling of the foot, which can be appreciated on radiographs. Initially subtle
fractures and bone mal‐alignment may be appreciated, which if unrecognized and untreated,
will progress to increasingly marked deformity with bone fragmentation and joint destruc-
tion, marked soft tissue swelling and bone resorption in the subacute stage. The process will
eventually stabilize, with remineralisation and then sclerosis of the bones and malunion of
the fractures in the deformed position. Rarely, the process may re‐­activate, going through
 9.2 ­Pathologie 163

the same sequence of destruction and repair with further deformity. The process may take
many months to complete and offloading is needed until the foot is stable – radiographic
demonstration of sclerosis and fracture union is useful in assessing this progress.
Neuropathic changes may manifest as arthropathy, dislocation, fracture, or a combina-
tion of these features. Study of bone mineral density in diabetic feet has demonstrated
peripheral osteopenia in those patients with a fracture pattern of neuropathy, but relatively
normal bone density in those with a dislocation pattern [10] and in those with neuropathy
but no arthropathy [11]. The fracture pattern of neuropathy was commonest in the ankle
and forefoot, whilst dislocations were commonest in the midfoot. [10]. The Charcot foot
commonly goes unrecognized until severe complications have occurred [12]. The mean
delay between first clinical presentation and diagnosis of a Charcot foot in diabetes was
29 weeks in one study [13]. Neuropathic changes in the foot have been divided into five
stages [14]; stage 0 is a clinical stage with a swollen, warm, and often painful foot. At this
stage radiographs are normal but bone scintigraphy is positive. Stage 1 has radiographic
abnormality including peri‐articular cysts, erosions, localized osteopenia, and diastases.
Stage 2 has joint subluxations, most commonly between the middle cuneiform and base of
the second metatarsal, which then spread laterally. Stage 3 has full dislocation and collapse
of the longitudinal arch of the foot. The case illustrated in Figure 9.12 demonstrates the
rapid progression from stage 0 to stage 3 that can occur. Stage 4 is the healed, stable end
result (Figure 9.13). This description applies to neuroarthropathy involving the midfoot.

(a) (b)

Figure 9.12 (a) Patient with a warm, swollen foot, thought to be cellulutis, radiographically
normal. (b) Three weeks later, repeat radiography demonstrates a neuropathic Lisfranc fracture
dislocation.
164 9 What Role for the Plain Radiograph of the Diabetic Foot?

Figure 9.13 Chronic stable neuropathic foot.

Figure 9.14 Neuropathic bone resorption resulting in a ‘sucked candy’ appearance to the residual
phalanges of the third fourth and fifth toes.

Metatarsophalangeal joint involvement by neuroarthropathy is also common, as is ­multiple

joint involvement [15]. Neuropathic bone resorption of the phalanges can also occur,
resulting in an appearance described as ‘sucked candy’ (Figure 9.14).

9.2.5 Gout
There is an increased risk of gout in patients with type 2 diabetes, though the relation-
ship between these conditions is complex [16]. The increased risk is due to co‐morbidi-
ties rather than diabetes per se. Radiographic features of gout are non‐specific in acute
 9.2 ­Pathologie 165

Figure 9.15 Extensive chronic tophaceous gout in a diabetic foot. There are multiple large
juxta-articular bone erosions with overhanging edges.

gout, with soft tissue swelling around the affected joint. In chronic gout juxta‐articular
bone erosions, characteristically with overhanging edges are seen (Figure 9.15.), and
tophi will produce slightly radio‐dense soft tissue masses, though dense calcification is
not usually seen.

9.2.6 Normal Appearances

Variation in the appearance of the foot and ankle on radiographs due to radiographic pro-
jections and exposure, the complexities of normal anatomy, variations of normal anatomy
between individuals and the sometimes gross abnormalities that may occur in diabetic feet
all contribute to the challenge of interpretation of radiological images. Additional (acces-
sory) ossicles are common in the foot and ankle (Figure 9.16), with over twenty recognized
and named accessory ossicles. Although two sesamoid bones are usually present under the
great toe, these can be bi‐ or tri‐partite and sesamoids can also occur under other toes.
Recognition of normal variants of radiographic appearances in the foot and ankle by refer-
ence to relevant texts is recommended [17]. Accessory ossicles or variations in the mor-
phology or alignment of the metatarsals and phalanges are clearly demonstrated on plain
radiographs. Whilst usually considered to be normal variants, and of no clinical signifi-
cance, these features may predispose to ulceration in diabetic feet, for example, an inter-
phalangeal accessory sesamoid in the great toe was present in 13 of 29 diabetic patients
with great toe ulcers [18]. Such normal variants are, however, no more common in diabet-
ics than the rest of the population [5].
166 9 What Role for the Plain Radiograph of the Diabetic Foot?

Figure 9.16 An accessory ossicle (normal variant) is present on the medial side of the great toe,
adjacent to the interphalangeal joint. In diabetic patients, such bony prominences can predispose
to ulceration.

9.2.7 Clinical Information

For the radiologist, adequate clinical information is essential in image interpretation. Even
with access to electronic records, a succinct clinical description with the radiology request
is invaluable. In our institute the medical illustration department is used to document
ulceration with clinical photographs, which are stored in the picture archive and commu-
nication system (PACS), where they are accessible by the radiologist. Correlation of the
photograph with the radiograph is an aid to radiological interpretation and also useful in
clinic‐radiological meetings.

9.3 ­Summary

The limited value of plain radiographs depicted in much of the published literature is
due to the sensitivity and specificity of a ‘blinded’ single examination for the diagnosis
of acute osteomyelitis or CN but is at odds with its widespread use. We advocate routine
use of plain radiography for initial diagnosis and serial radiography for follow‐up and to
avoid overlooking initially occult acute pathology, even if additional imaging investiga-
tions, such as MR scanning is being undertaken. High quality radiography utilizing
  ­Reference 167

high definition ­imaging plates and additional radiographic views targeted to the region
of interest is required, this can be promoted by a regular multidisciplinary team meet-
ing to which the radiographers, radiologists, podiatrists, nurses, and clinicians should
contribute. Where the diagnosis remains uncertain, radiographs should be repeated at
10–14 day intervals until the diagnosis becomes clear or the symptoms and signs that
precipitated the initial clinical concern have completely resolved. MR scanning or
nuclear medicine tests can be performed where plain radiographs are not sufficient or
where treatment decisions cannot await the 10–14 day interval between radiographs.
This could be, for example, the demonstration of proximal extent of osteomyelitis where
amputation is being considered, or to demonstrate the presence of and size, location
and extent of an abscess cavity.

­References

1 Edelson, G.W., Armstrong, D.G., Lavery, L.A., and Caicco, G. (1997). The acutely infected
diabetic foot is not adequately evaluated in an inpatient setting. J. Am. Podiatr. Med. Assoc.
87: 260–265.
2 Markanday, A. (2014). Diagnosing diabetic foot osteomyelitis: narrative review and a
suggested 2‐step score‐based diagnostic pathway for clinicians. Open Forum Infect. Dis. 1
(2).
3 Mayfield, J.A., Caps, M.T., Boyko, E.J. et al. (2002). Relationship of medial arterial
calcinosis to autonomic neuropathy and adverse outcomes in a diabetic veteran
population. J. Diabetes Complicat. 16: 165–171.
4 Armstrong, D.G., Hadi, S., Nguyen, H.C., and Harkless, L.B. (1999). Factors associated with
bone regrowth following diabetes‐related partial amputation of the foot. J. Bone Joint Surg.
Am. 81: 1561–1565.
5 Cavanagh, P.R., Vickers, K.L., Young, M.J. et al. (1994). Radiographic abnormalities in the
feet of patients with diabetic neuropathy. Diabetes Care 17: 201–209.
6 Holmes, G.B. Jr. and Hill, N. (1994). Fractures and dislocations of the foot and ankle in
diabetics associated with Charcot joint changes. Foot Ankle Int. 15: 182–185.
7 Dinh, M.T., Abad, C.L., and Safdar, N. (2008). Diagnostic accuracy of the physical
examination and imaging tests for osteomyelitis underlying diabetic foot ulcers: meta‐
analysis. Clin. Infect. Dis. 47: 519–527.
8 Aragón‐Sánchez, J., Lipsky, B.A., and Lázaro‐Martínez, J.L. (2011). Diagnosing diabetic
foot osteomyelitis: is the combination of probe‐to‐bone test and plain radiography
sufficient for high‐risk inpatients? Diabet. Med. 28: 191–194.
9 Demirag, B., Tirelioglu, A.O., Sarisözen, B., and Durak, K. (2004). (Necrotizing fasciitis in
the lower extremity secondary to diabetic wounds). Title in original lang. Bacakta diyabetik
yaralara bagli nekrozitan fasiit. Acta Orthop. Traumatol. Turc. 38: 195–199.
10 Herbst, S.A., Jones, K.B., and Saltzman, C.L. (2004). Pattern of diabetic neuropathic
arthropathy associated with the peripheral bone mineral density. J. Bone Joint Surg. Br. 86:
378–383.
11 Young, M.J., Selby, P.L., Marshall, A. et al. (1995). Osteopenia, neurological dysfunction,
and the development of Charcot neuroarthropathy. Diabetes Care 18: 34–38.
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12 Caputo, G.M., Ulbrecht, J., Cavanagh, P.R., and Juliano, P. (1998). The Charcot foot in
diabetes: six key points. Am. Fam. Physician 57: 2705–2710.
13 Pakarinen, T.K., Laine, H.J., Honkonen, S.E. et al. (2002). Charcot arthropathy of the
diabetic foot. Current concepts and review of 36 cases. Scand. J. Surg. 91: 195–201.
14 Sella, E.J. and Barrette, C. (1999). Staging of Charcot neuroarthropathy along the medial
column of the foot in the diabetic patient. J. Foot Ankle Surg. 38: 34–40.
15 Scartozzi, G. and Kanat, I.O. (1990). Diabetic neuroarthropathy of the foot and ankle. J.
Am. Podiatr. Med. Assoc. 80: 298–303.
16 Wijnands, J.M., van Durme, C.M., Driessen, J.H. et al. (2015). Individuals with type 2
diabetes mellitus are at an increased risk of gout but this is not due to diabetes: a
population‐based cohort study. Medicine (Baltimore) 94: e1358.
17 Keats, T.E. and Anderson, M.W. (eds.) (2012). Atlas of Normal Roentgen Variants that May
Simulate Disease, 9e. Elsevier.
18 Boffeli, T.J., Bean, J.K., and Natwick, J.R. (2002). Biomechanical abnormalities and ulcers
of the great toe in patients with diabetes. J. Foot Ankle Surg. 41: 359–364.
 169

10

Advanced Cross-Sectional Radiology-Ultrasound,

Computed Tomography and Magnetic Resonance
Imaging of the Diabetic Foot
Aparna Komarraju1 and Avneesh Chhabra2,3
1
Radiology, Formerly, University of Texas Southwestern Medical Center, Dallas, TX, USA
Currently, Beth Israel Deaconess Medical Center, Boston, MA
2
Radiology & Orthopedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
3
Adjunct faculty-Johns Hopkins University, MD; Walton Centre of Neurosciences, Manchester, UK

KEY POINTS
1) Ultrasound imaging is useful to diagnose fluid collections and guide minimally invasive
­interventional procedures of the foot, such as abscess drainage and injection of painful joints, etc.
2) Computed tomography (CT) imaging identifies necrotic bone and foot malalignment in the
setting of Charcot neuroarthropathy as well as bony sequestrum, cortical destruction, abscess,
and foreign body in the setting of osteomyelitis.
3) Conventional magnetic resonance (MR) imaging is the modality of choice for pedal osteomy-
elitis and accurately evaluates the deep and longitudinal extent of the infection.
4) Advanced MR imaging using diffusion weighted technique accurately identifies abscess in the
mound of soft tissue edema in lieu of the intravenous contrast imaging.
5) Emerging CT techniques, such as spectral or dual source CT are helpful in reducing the metal
artefact and may aid in bone marrow assessment on iodine contrast maps.

10.1 ­Introduction

The National Diabetes Statistics Report, a report generated by Centers for Disease Control
and Prevention (CDC) estimated that 30.3 million people, which amounts to 9.4% popula-
tion of the US population, were suffering from diabetes in 2015. In 2015, an estimated 1.5
million new cases (6.7 per 1000) were diagnosed with diabetes in the adult population aged
18 years and above. An estimate of 33.9% (84.1 million) of the North American adult popu-
lation of the age 18 years or older had pre‐diabetes in 2015 based on their fasting blood
glucose levels or HbA1C levels. The risk factors for diabetes‐related complications from
data between 2011 and 2014 included smoking (current and former smokers), overweight
and obesity, sedentary lifestyle, high blood pressure, hypercholesteremia, and hyperglyce-
mia. In 2014, a total of 7.2 million hospital discharges were reported with diabetes and

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
170 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

diabetes‐related complications including cardiovascular disease, cerebrovascular acci-

dents, lower extremity amputations, diabetic ketoacidosis, and renal failure. Diabetes was
reported as the seventh leading cause of death in 2015. The estimated total annual health
care costs in the USA in the year 2015 from direct and indirect consequences of diagnosed
diabetes was about $245 [1].

10.2 ­Pathophysiology of Diabetic Foot Disease

Diabetic foot disease can result from neuropathic, vascular, traumatic, or secondary infectious
causes [2, 3]. Diabetic neuropathy is one of the life‐threatening complications involving both
the peripheral and autonomic nerves, seen in almost half of the population suffering from
diabetes. The risk increases with duration of exposure of the patient to hyperglycaemia [2].
Diabetic Charcot osteoarthropathy results in destructive changes in the feet associated with
underlying neuropathic deficits. The incidence of Charcot foot in patients with diabetes mel-
litus is approximately 5% in their lifetime [3]. Many pathophysiologic pathways have been
proposed, which act in either isolation or combination. These include oxidative stress,
advanced glycation products, low‐grade inflammation (RANKL, receptor activator of nuclear
factor kappa‐Β ligand pathway, cytokines), neovascularization of vasa vasorum supplying the
peripheral nerves, and micro‐ and macro‐vascular trauma with underlying loss of sensitivity
to pain, temperature, and proprioception resulting in repeated injuries to the feet. Secondary
infection of such wounds result in osteomyelitis and abscess formation [4–6]. Distinguishing
destructive neuropathic foot lesions from osteomyelitis can be challenging clinically. Early and
accurate diagnosis of diabetic foot complications can reduce patient morbidity, complications,
health care costs, and limb amputations whilst potentially improving wound healing and
quality of life [7]. Imaging plays an important role in the diagnosis and follow‐up of diabetic
pedal complications. Further discussion will focus on various imaging modalities available to
supplement clinical and laboratory findings in this domain for improved patient diagnosis and
management.

10.2.1 Imaging Modalities

Multiple imaging modalities are available for the evaluation of diabetic foot including plain
radiography, ultrasound (US), computed tomography (CT), magnetic resonance imaging
(MRI), nuclear medicine scintigraphy (including white blood cell or indium labelled scan
and single photon emission computed tomography – SPECT), SPECT–CT, and positron
emission tomography (PET).
Plain radiographs are widely available, inexpensive compared to the other modalities and
are useful in demonstrating major structural abnormalities, fractures (Figure 10.1), cortical
destruction osteomyelitis, soft tissue swelling, gas, or foreign bodies [8]. Ultrasound is a
radiation free modality that can be used to image and identify fluid collection in the soft
tissues (Figure 10.2), joint effusion, foreign body and tenosynovitis as well as to guide inter-
ventions [9]. CT is more specific in identifying subtle bony erosions, osteopenia, malalign-
ments (Figure 10.3), soft tissue collections, calcifications, bony sequestrum, and foreign
bodies [10]. MRI is the current standard modality for identifying the extent of soft tissue
(a) (b)

Figure 10.1 Anteroposterior (AP) radiographs of right foot in a DM patient obtained two years
apart with complaints of increasing foot pain and swelling. Notice increasing swelling and second
metatarsal fracture (arrow) with Lisfranc subluxation in the subsequent radiograph (b) with normal
alignment in the initial radiograph (a).

(a) (b)

(c)

Figure 10.2 48 year old man with DM presenting with foot and knee swelling with pain. Grey scale (a)
and colour doppler (b) images of the anterior knee show a complex collection suggesting an abscess with
peripheral vasculairty (arrows). Frank pus was drained from the lesion. On the contrary, grey scale image
(c) of the ankle demonstrate hypoechoic oedema in the soft tissues (arrow) without a collection.
172 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

(a)

(b) (c)

Figure 10.3 59 year old man with DM and Charcot foot. Lateral radiograph (a), corresponding
sagittal CT bone window reconstruction (b) and volume rendered reconstruction (c) images show
extensive bone destruction, debris, osteopenia, and malalignments with fatty atrophy of the
muscles typical of a long standing diabetic Charcot foot.

(a) (b)

Figure 10.4 DM and Charcot foot with reactive bone marrow oedema. Lateral radiograph (a) and
corresponding sagittal fat suppressed T2-weighted (fsT2W) MR (b) image shows talar dislocation
with hyperintense reactive edema of the hindfoot and midfoot bones (arrows).

and bone marrow changes in the diabetic foot. MRI also enables differentiation of osteomy-
elitis from neuroarthropathy and reactive bone marrow edema (Figure 10.4) [11–13].
Nuclear bone scintigraphy has shown to have negative predictive value in excluding osteo-
myelitis. The accuracy and positive predictive value is at best moderate in the presence of
underlying surgery or arthropathic changes [12]. SPECT–CT can improve anatomic
 10.2 ­Pathophysiology of Diabetic Foot Diseas 173

(a) (b) (c)

(d) (e)
100

0
RLT 111-Indium RLT 99m Technetium

Figure 10.5 49 year old man with diabetes mellitus, Charcot foot, and heel ulcer with concern for
osteomyelitis. AP and lateral radiographs (a and b) with corresponding coronal CT bone window
reconstruction (c) demonstrate advanced Charcot changes of the midfoot (arrows). (d) Fused
Indium-111 images reveal a focal area of Indium-111 uptake in the subcutaneous and deep tissues
of the plantar surface of the foot overlying the calcaneus, without bony involvement, compatible
with soft tissue infection (arrow). (d) Dual isotope images demonstrate matched uptake in the
hindfoot within the areas of Charcot change, without evidence of osteomyelitis.

r­ esolution whilst adding 3D capabilities to imaging (Figure 10.5). However, due to cost and
limited spatial resolution, SPECT, and PET imaging has not gained much traction in this
area [14]. Further discussion will focus on the advantages and limitations of the commonly
employed imaging modalities for evaluation of the Diabetic foot complications.

10.2.1.1 Plain Radiographs

Plain radiography is an economical and widely available screening modality, often the
first test of choice. Findings on plain radiography may prompt additional tests for
further evaluation and better characterization, since bone marrow and soft tissue
evaluations are limited on radiography. Arthropathy and foot malalignment are easily
apparent on the plain radiographs (Figures 10.1, 10.3–10.5). Soft tissue swelling,
ulceration, and air suggesting underlying necrotizing fasciitis/gas gangrene, or the
174 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

presence of radiopaque foreign body are some of the findings that are valuable and
prompt further tests with cross‐sectional imaging modalities. Most of the radiopaque
foreign bodies like metal or glass are identified on the X‐rays, except for some wood
splinters. MRI aids in evolution of the deep extent of the soft tissue infection [15, 16].
Plain film changes of Charcot foot are periarticular cysts, ­erosions, joint destruction,
subluxations, and dislocations leading to arch collapse [17]. The neuropathic foot
changes can occur in different areas of the foot, typically more common in the mid-
foot area, e.g. Chopart and Lisfranc joints. More proximal changes in the foot, i.e. in
posterior subtalar or tibiotalar joints, are associated with greater morbidity. Resultant
complete collapse of the mid foot along with a disorganized joint with debris and
intra‐articular loose bodies’ frequently progress to perforation of the plantar fascia
resulting in a rocker bottom deformity [18]. Early changes of Charcot foot, i.e. sub-
chondral fractures are occult on the plain radiography, and MRI is a better tool to
assess these changes as focal hypointensities in the mound of bone marrow edema
(Figure 10.6). Findings demonstrating osteolysis, cortical sclerosis, and bony remodel-
ling are better appreciated on the radiographs, but these are late stage findings. Whilst
cortical destruction at the site of soft tissue ulcer or infection is a confirmatory sign of
osteomyelitis, midfoot destruction from osteomyelitis versus neuropathy can be chal-
lenging to distinguish on plain films alone. Thus, for the accurate diagnosis of deep
infection, osteomyelitis, neuropathy versus infection, extent of the devitalized tissue,
etc., additional cross‐sectional imaging is warranted [19].

(a) (b)

Figure 10.6 DM with foot pain. AP radiograph (a) shows foot swelling, Corresponding coronal
fsT2W MR (b) image shows extensive soft tissue and reactive bone marrow edema with occult
subchondral hypointense fractures (arrows).
 10.2 ­Pathophysiology of Diabetic Foot Diseas 175

10.2.1.2 Ultrasound
Ultrasonography is another in‐expensive test that can be performed at the bedside without the
risk of ionizing radiation. Soft tissue oedema and thickening with or without hyperaemia on
Doppler imaging favour cellulitis, which on ultrasound (US) demonstrates a cobblestone or
hypoechoic pattern with soft tissue stranding traversing the subcutaneous planes (Figure 10.2c)
[20]. A focal hypoechoic collection with or without floating internal debris, representing an
abscess is easily identified on US and guided aspiration can be performed real time. Ultrasound
has the advantage of real time visualization of the complete length and course of the needle
and in detecting any residual fluid pocket post‐aspiration. Other advantages of US include
portability, no claustrophobia, multiple areas in the same limb can be interrogated and probe
tenderness can be tested in the same setting. Diabetics are also prone to increased risk of devel-
oping mechanical or infectious tenosynovitis [21]. US features of tendinopathy and tenosyno-
vitis include thickened, non‐compressible tendons with circumferential fluid collection in the
tendon sheath and increased flow on Doppler imaging. Thickening of the intra‐articular syn-
ovium with increased Doppler flow and associated peri‐articular fluid collections is suggestive
of synovitis and when accompanied by appropriate clinical features, a septic joint. In the case
of an abscess, a hypo or mixed echogenic fluid collection with a thick rim of capsule and
increased Doppler flow is seen (Figure 10.2a and b) [22]. Early aspiration and treatment of
such collections are important, since sepsis in a joint can progress quickly to cartilage and joint
destruction. Pyomyositis is seen as a mixed echogenicity of the muscle with possible focal col-
lections within the muscle and increased Doppler flow. US also plays a pivotal role in identify-
ing foreign objects like wood that cannot be seen on X‐rays.
Diabetes is the highest risk factor for the development of peripheral arterial disease
(PAD) [23, 24]. The simplest way to assess PAD in longstanding diabetics is ankle brachial
index (ABI). An ABI of 0.9–1.3 is normal and less than 0.4 indicates severe arterial flow
obstruction. US plays a role in patients with abnormal ABI in assessment of severity and
location of stenosis, Doppler waveform patterns, peak systolic velocity, resistive index, pul-
satility index, intimal thickening atheromatous plaques, findings, and parameters, which
are very useful for the vascular surgeons in the evaluation and management of the diabetic
patients with PAD. The normal arteries with no PAD demonstrate triphasic Doppler wave-
forms. Mono‐ and biphasic waveforms with spectral broadening indicate severe occlusive
disease that may require intervention [25]. A quantitative analysis of the Doppler wave-
form along with the information on the resistance to the blood flow in a vessel is calculated
as the resistive index. Lower resistive index and pulsatility index plus skin changes indicate
distal limb ischemia [26]. Some studies suggest that in patients with diabetes and polyneu-
ropathy, pulsatility index might be a better indicator of ischemia than ABI [27]. Whilst
Monckeberg calcifications are common in the media of peripheral vessels in diabetes, the
narrowing is more commonly caused by atherosclerotic changes resulting in the thicken-
ing of the intima and plaque formation narrowing the vascular lumen and causing flow
disturbances with resultant stasis, clot formation, thrombosis, and occlusion [26, 27].

10.2.1.3 Computed Tomography (CT)

CT scan has the advantages of wide availability, less cost than MRI, better soft tissue reso-
lution compared to plain radiographs, however, is still limited by exposure to ionizing
radiation. Although its application in detecting marrow oedema and subchondral
176 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

f­ ractures is limited, malalignments (Figure 10.3) and cortical destruction of osteomyeli-

tis can be easily identified. Patches of medullary lucencies along with cortical break-
through and periosteal reaction at the site of ulceration are imaging signs suggestive of
acute osteomyelitis (Figure 10.7). Subacute osteomyelitis may be seen as hypodense
intramedullary collection with ill‐defined wide‐zone fading surrounding sclerosis. It is
called Brodie’s abscess similar to plain radiographs. CT imaging is also good at identify-
ing bony sequestrum and better than radiographs [28]. Contrast enhanced CT aids in
evaluation of the soft tissue details in greater depth. Differentiating cellulitis from simple
oedema is possible based on enhancement of soft tissues. A rim enhancing abscess can
be difficult to differentiate from a simple fracture related hematoma or irregular devital-
ized tissue. Clinical correlation with elevation of ESR, CRP, and white cell counts with
leftward shift and bands are helpful signs in confirming the infective nature of the collec-
tion. Cortical destruction with ESR of more than 70–75 is confirmatory of osteomyelitis.
CT scan is also more sensitive than X‐rays in recognizing early cortical erosions, soft tis-
sue air, foreign bodies and sinus tracts. The disadvantage of CT scans are use of ionizing
radiation and beam hardening artefact that can mask small fluid collections immediately
next to the bone or adjacent to a prosthesis in post‐operative cases. However, using high
KVp to obtain thinner sections and reconstruct into thicker slabs and using iterative
reconstruction software can minimize the beam hardening artefacts.
Non‐surgical interventions for Charcot foot include rest, brace, splint, and custom foot-
wear. Surgery is reserved for patients with significant deformity predisposing to ulceration,
failed conservative measures, and increased risk of infection or ulceration. If the source of
an ulcer at the plantar aspect of foot is a collapsed piece of bone that is causing constant
pressure and ulceration, osteotomy may be performed, wherein; the protruding piece of
bone is removed. If there is complete mid foot collapse, surgical procedures to realign and
stabilize the midfoot arch known as midfoot realignment arthrodesis may be performed
[29, 30]. Similarly, realignment with arthrodesis of hind foot and ankle can also be
­performed as a part of limb saving surgery in patients with severe foot instability and
deformity [31]. It is essential that the patients undergoing surgery be followed up for
­complications from surgery. Due to underlying diabetes, the infection rates are high and

(a) (b)

Figure 10.7 DM with Charcot foot, plantar ulcer and suspected deep infection. Sagittal
reconstructed CT (a) and corresponding sagittal fsT2W MR (b) images show plantar ulceration with
plantar fascial disruption and contigous erosion of the cuboid (arrow). MR image confirms
extensive midfoot and hindfoot osteomyelitis, septic arthritis and fluid collections.
 10.2 ­Pathophysiology of Diabetic Foot Diseas 177

the infection predisposes to higher surgical failure rates. Other common complications that
need to be evaluated are for prosthesis loosening, fractures of prosthesis and at the peri‐
prosthetic regions. Although, beam hardening artefact from local metal limits evaluation,
post‐operative patients must be carefully evaluated for infection, soft tissue air, sinus tract,
ulcers, periosteal reaction, lucencies around the prosthesis, peri‐prosthetic fractures or
subtle collections adjacent to the joint/hardware. Plain X‐rays can detect soft tissue swell-
ing and loosening of hardware in most cases. MRI evaluation is limited due to susceptibil-
ity artefact from metal. Ultrasound may be used for the evaluation of fluid collections
around the prosthetic joints. Combined labelled white blood cell along with 99 m
Technetium Sulphur colloid imaging is useful in identifying prosthetic infections. Sulphur
colloid accumulates in the normal marrow, whereas WBC accumulates in the normal mar-
row as well as at the sites of infection. Therefore, if there is activity of labelled WBC around
the prosthetic joints, an infection can be suspected [32].

10.2.1.4 Magnetic Resonance Imaging (MRI)

Early stages of Charcot diabetic neuroarthropathy demonstrate marrow oedema with sub-
chondral fractures (Figure 10.6) and periarticular enhancement on post‐contrast studies;
swelling of soft tissues adjacent to the joints with loss of normal fat planes, subchondral
cysts and joint effusions. No bony deformity is noted in early stages of neuroarthropathy. In
subacute stages, articular erosions and resorption of the articular surfaces of the bones is a
hallmark finding. In chronic stages, marrow oedema subsides significantly with only mini-
mal residual oedema. In chronic stages bony deformity, osteolysis with destruction, joint
subluxations, dislocations along with joint effusions are noted (Figure 10.8) [16, 17, 33–36].
American College of Radiology (ACR) recommendations suggest plain radiography as the
first line of investigation as a part of work up in patients with diabetes complaining of foot
pain [37]. On MRI, diffusely low marrow signal on all sequences with subchondral cysts,

(a) (b)

Figure 10.8 DM with Charcot foot and no osteomyelitis. Sagittal T1W (a) and corresponding
sagittal fsT2W (b) MR images show extensive destruction of talus and Chopart joints with fluid
collections and reactive bone marrow and soft tissue edema. Absence of ulceration or
communicating sinus tract virtually excludes the diagnosis of osteomyelitis.
178 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

(a) (b)

Figure 10.9 DM with neuropathic muscle denervation changes. Sagittal fsT2W (a) and axial T1W
(b) MR images show diffuse foot muscle oedema like signal (arrow in A) and complete fatty
replacement (arrow in B) without fascial oedema or haemorrhage confirming denervation changes.

bony proliferation, debris, intra‐articular loose bodies, and subluxation/dislocation of the

joints is seen in later stages of chronic neuropathic osteoarthropathy [16, 38]. The Charcot
changes are classically located in the mid‐foot and are usually bilateral. Regional plantar
muscle denervation changes are apparent with oedema like signal on fat suppressed T2
weighted (fsT2W) images with or without fatty replacement and atrophy (Figure 10.9). The
tibial and plantar nerves are also hyperintense with or without thickening on fsT2W
images. MR neurography in addition demonstrates these abnormal nerves conspicuously
along their long axis and similar neuropathic changes can also be present in the sciatic
nerve proximally in the leg [39] or in the lumbosacral plexus (lumbosacral amyotrophy).
Foot deformities caused by bony osteolysis, subluxations, dislocations, and collapse of
the arch can cause altered biomechanics, friction, and further result in ulcerations in the
mid‐foot. Nearly all infections to the underlying bones in patients with diabetes are from
contiguous spread from superficial skin infection or ulceration. Accordingly, the MR exam-
ination must be limited to the area of concern and the imaging is best performed to sepa-
rately include fore‐foot and mid‐foot, or hind‐foot and ankle, respectively with a marker
over the ulcer whenever possible. Since fsT2W imaging is highly sensitive for bone marrow
oedema, absence of oedema (bright signal) on these images virtually excludes osteomyeli-
tis. However, in the presence of bone marrow oedema on fsT2W imaging, corresponding
hypointense signal changes on T1W non‐fat suppressed sequence increases the specificity
in diagnosis of osteomyelitis. One should also look for cortical destruction (loss of dark
cortical margin), periostitis, subperiosteal fluid collection, or intra‐osseous abscess in the
vicinity of ulcer or sinus tract, multiple key signs that confirm the presence of osteomyelitis
(Figure 10.7). Oedema on fsT2W imaging with normal fatty (hyperintense) signal on T1W
imaging reflects reactive oedema due to stress or regional soft tissue infection. Technical
pitfalls, such as failure of fat suppression due to extremity curvatures or local metal in the
area are not uncommon on frequency selective fat suppression techniques. A short inver-
sion time inversion recovery (STIR) sequence can be very useful in distal extremity imaging
or on lower field MR scanners to obtain superior fat signal suppression. However, this
sequence generally exhibits lower signal to noise ratio [40]. Newer Dixon‐based MR tech-
niques exhibit high signal to noise ration and produce multiple images from the same
sequence, namely water image (similar to fsT2W image but superior and homogeneous fat
 10.2 ­Pathophysiology of Diabetic Foot Diseas 179

(a) (b) (c)

Figure 10.10 T2 Dixon MR imaging of the same case as Figure 10.8. DM with Charcot foot.
In-phase (a), water (b) and opposed-phase (c) axial MR images. Notice more sharply defined eroded
bony margins of the neuropathic joints (arrows) on the opposed-phase image (c).

suppression for identifying bone marrow edema), fat image, in‐phase image (with water
and fat in phase‐ similar to the non fat suppressed T2W image), and opposed‐phase image
(with water and fat out of phase, OP). The OP images are excellent in identifying subchon-
dral fractures and margins of the eroded bones as well as fatty infiltration of denervated
muscles (Figure 10.10). Use of multiplanar imaging tailored to the location of the ulcer aids
in better evaluation, for example, medial hindfoot lesions are seen best in the axial and
coronal planes and calcaneal lesions or distal toe lesions are best identified in the sagittal
plane. It is interesting to notice that cysts in neuropathic joints on fsT2W imaging or the
bone contour on T1W imaging disappear (Ghost sign) when there is a wave of osteomyelitis
or spreading foot infection. These cysts and bones are re‐demonstrated as the infections
heal. Intravenous gadolinium contrast is helpful in characterization of the Diabetic foot
lesions. The contrast enhancement is helpful to distinguish cellulitis (enhancing) from
bland subcutaneous oedema (non‐enhancing), osteomyelitis (marked enhancement) from
reactive oedema (minimal enhancement), and abscess (intense rim enhancement) from
haematoma, adventitial bursitis, or bland fluid collection (minimal or no peripheral
enhancement). On the contrary, non‐enhancement of a bright lesion on fsT2W imaging
indicates devitalized soft tissue or bony tissue (Figure 10.11). Contrast enhancement is also
useful in finding sinus tract, foreign body, and ulceration. However, contrast administra-
tion is to be avoided in patients with renal failure or glomerular filtration rate of <30 ml/
min/1.73 m2 [41, 42]. With new macrocyclic contrast agents, gadolinium retention in the
body, particularly nephrogenic systemic fibrosis risk has not been reported.
Another contrast mechanism without administration of exogenous gadolinium is diffusion
weighted imaging (DWI), which can help in excluding or identifying small abscesses in
patients with diffuse cellulitis in the area of concern [13] (Figures 10.11 and 10.12). DWI
detects Brownian movement of the water molecules with a ‘b’ value (diffusion moment)
characterizing the sensitivity to detect restricted diffusion. Normal random movement of
water molecules in the tissues causes opposing gradients and dephasing resulting in loss of
signal on DWI. Higher the b value, the greater is the sensitivity to detect restricted diffusion,
which can occur in the setting of high cellularity or viscous pus. Apparent diffusion coeffi-
cient (ADC) is obtained by using different (at least two) b values and quantifies the loss of
signal. Restricted diffusion is seen as bright signal on DWI and corresponding dark signal on
180 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

(a) (b) (c) (d)

(e) (f) (g)

Figure 10.11 DM with plantar ulcer and suspected deep infection. Sagittal T1W (a) and fsT2W
(b) MR images show plantar ulcer and extensive midfoot and hindfoot osteomyelitis changes.
Corresponding sagittal post-contrast fsT1W (c) and subtraction (d) images confirm intense bone
enhancement and non-enhancing devitalized tissue (arrows) underneath the ulcer. Diffusion
weighted (DWI) images-b0 (e), b600 (f) and apparent diffusion coefficient (ADC-G) similarly show
bone marrow oedema and no restricted (dark) areas to suggest a drainable abscess.

(a) (b) (c) (d)

Figure 10.12 DM with anterolateral ankle soft tissue swelling. Axial T2W (a) MR image shows
diffuse soft tissue oedema, mostly along the lateral ankle. Diffusion weighted (DWI) images-b0 (b),
b600 (c) and ADC (d) show an area of restriction (dark on ADC, arrows) confirming presence of a
drainable abscess.

ADC [43]. Simple oedema, lymphedema, and treated abscesses do not show restricted
diffusion (dark on higher b value, b = 600–800 s/mm2, and bright on ADC). Abscesses
show restricted diffusion and are bright on lower (b = 0) and brighter on higher b value
(b = 600–800s/mm2) and dark on ADC maps (Figure 10.12). Haemorrhagic fluid, reactive
marrow oedema, cellulitis, granulation tissue, wet gangrene, muscle denervation, and myo-
pathy show T2 shine through artefact (bright on lower and higher b value and ADC). Dry
gangrene, fibrosis, calcium, and fat have low water content and therefore are dark on DWI
 10.2 ­Pathophysiology of Diabetic Foot Diseas 181

and ADC. Thus, ADC provides a quantitative measure, e.g. in a soft tissue or intra‐osseous
abscess, it can be as low as 0.6–0.8. In the setting of septic arthritis, due to the admixture of
the synovial and infected fluids, it is generally higher in the range of 1.5–1.8 as opposed to the
simple joint fluid (ADC = 2.5–3.0). In addition, ADC can be followed to judge the response to
antibiotic treatment. With successful treatment, DWI signal decreases and ADC value reaches
normal range. ADC restriction also differentiates bland from infected tenosynovitis
(Figure 10.9) with restricted diffusion along the tendon sheath from the pus and viscous col-
lections confirming an infective tenosynovitis [44]. The major limiting factor, however, in
superficial infections is ghosting artefact from low signal to noise ratio and inadequate fat
suppression. Subcutaneous air droplets can also result in susceptibility artefact and image
distortion [13, 45, 46]. New multi‐segmented read‐out and spin echo type DWI is superior in
mitigating the above artefacts. However, it takes a longer time for acquisition.
Deep infections like necrotizing fasciitis can show subcutaneous gas; fascial enhance-
ment in viable tissue and DWI is useful in identifying interfascial or intramuscular
abscesses (also called pyomyositis). Again, air can cause some artefacts and image distor-
tion resulting in difficult interpretation [47, 48]. DWI is best interpreted in conjunction
with conventional MR imaging as it can supplement the diagnosis, but it does not not
replace the routine imaging. Osteomyelitis on MRI is seen as hypointense signal on T1W,
hyper intense signal on STIR/fsT2W and can be differentiated from the reactive marrow
oedema by absence of T1 hypointensity or the latter being limited to the subcortical bone
in the latter. DWI signal is dark in the normal bone and becomes hyperintense in the set-
tings of reactive marrow oedema and intraosseous or subperiosteal abscess. ADC values in
reactive marrow edema are 1.4–1.9 whilst in osteomyelitis, it is 0.6–1.1 (Figure 10.13).
Microangiopathy in diabetes can cause muscle oedema, ischemia, infectious, or inflam-
matory myositis and denervation. Muscle oedema like signal is seen in all of the conditions
on fsT2W imaging. A bright signal on DWI and corresponding dark on ADC helps differen-
tiate muscle abscess from ischemia/myositis. The imaging findings should be correlated to
the patient’s clinical condition and laboratory values including ESR, WBC, and CRP. As
opposed to the patchy intramuscular and/or fascial oedema of diabetic myositis, denerva-
tion change in muscle is diffuse with absence of fascial oedema or haemorrhage, and pres-
ence of fatty replacement and/or atrophy (Figure 10.9) [47, 48]. Diffusion tensor imaging
(DTI) in such cases can show abnormality of the neural tracts and altered quantitative
parameters of the nerve, e.g. increased ADC and decreased fractional anisotropy [49].

10.2.2 Future Directions

With widespread use of cross‐sectional imaging, accurate diagnosis of diabetic complica-
tions is being made. However, the optimal timing of discontinuing antibiotic treatment is
not established. Using surrogate imaging markers, such as T2 signal intensity ratio, degree
of contrast enhancement, ADC measurements, there is a potential to perform outcomes
analysis and determine the stopping rules of treatment. Newer modalities, such as dual
source and spectral CT are available. These scanners use multiple X‐ray energies or multi-
ple rows of radiation detectors with different attenuation properties to produce multiple
image contrasts. Thus, iodine and water maps can be created and potentially presence or
absence of marrow enhancement similar to MRI can be assessed by using low dose CT
contrast (Figure 10.14). In addition, effective Z (molecular weight) map can be created to
182 10 Advanced Cross-Sectional Radiology-Ultrasound, Computed Tomography

(a) (b)

(c) (d) (e)

Figure 10.13 47 year old woman with DM, great toe swelling and suspected osteomyelitis. Axial
T1W (a) and fsT2W (b) MR images show diffuse soft tissue oedema with bone marrow oedema of
the first metatarsal shaft and surrounding fluid collection. The patient could not receive
intravenous contrast due to poor renal function. Diffusion weighted (DWI) images- b0 (c), b600 (d)
and ADC (e) show areas of restriction (dark on ADC, arrows) confirming the presence of periosteal
and regional abscesses.

(a) (b) (c)

Figure 10.14 Plantar heel ulcer and suspected osteomyelitis. The patient couldn’t undergo MRI due
to contraindicated pacemaker. Sagittal reconstructed spectral CT image (a) in soft tissue window shows
the ulcer (arrow). Corresponding iodine only fused image (b) shows no iodine uptake in the underlying
calcaneus or the subcutaneous tissues with preserved bony cortex, thereby excluding osteomyelitis.
The fused effective Z map (c) shows no crystals or bone marrow oedema/enhancement.
  ­Reference 183

identify the crystals (monosodium urate or calcium) and calculate the weight of the miner-
als or soft tissues in question. Furthermore, in the setting of prosthesis, metal artefacts can
be reduced using this advanced imaging for improved image quality and interpretation.
To conclude, Diabetes mellitus is exceedingly prevalent multisystem disease involving
multiple organs and resulting in various musculoskeletal complications. Although imaging
of diabetes related musculoskeletal complications are challenging to interpret, use of cross‐
sectional imaging as a supplement to the plain radiography and correlation to the clinical
findings provides important diagnostic information, which is essential for timely and
appropriate management of these patients.

­Disclosures

AC receives royalties from Jaypee and Wolters. AC also serves as consultant with ICON
Medical and Treace Medical Concepts. Inc.
The authors do not report any conflict of interest.

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 187

11

Gait and Exercise Training in Diabetic Peripheral

Neuropathy
Neil D. Reeves
Research Centre for Musculoskeletal Science and Sports Medicine, Department of Life Sciences, Faculty of Science and
Engineering, Manchester Metropolitan University, Manchester, UK

11.1 ­Introduction

This chapter will discuss the movement problems that affect gait as a result of diabetic
peripheral neuropathy and how exercise may act to alleviate some of these issues. The
structural and functional changes to the diabetic foot are an important factor in how the
person with diabetes stands and moves around their environment. There are also, however,
a number of other important factors that affect walking which are altered with the onset of
diabetic peripheral neuropathy. Sensory and motor system impairments particularly affect-
ing the lower limbs occur with diabetic peripheral neuropathy and markedly affect how a
person walks, how efficient they are, and their level of unsteadiness. The way a patient
with diabetic peripheral neuropathy walks, along with a number of other factors, will also
determine the propensity for the development of diabetic foot ulcers. Although this is a
major issue, the focus of this chapter is on aspects of gait linked to unsteadiness and the
reader is directed to other reviews for a discussion on gait and foot ulceration [1–3]. The
term gait describes the manner in which a person walks and this can actually be measured
in great detail using a range of different experimental techniques that typically take place
within the gait laboratory.

11.2 ­Gait Characteristics of People with Diabetes

People with diabetes exhibit some very well-defined gait characteristics, which have
been widely described in the recent literature. People with diabetes walk more slowly
and are described as having a ‘more cautious’ approach to walking compared to their
age‐matched counterparts without diabetes [4, 5]. This slower gait and more cautious
strategy is ­characterized by taking shorter steps, having a wider stance and walking with
a ‘stiffer gait’ associated with less flexed lower limb joints. These gait alterations have

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
188 11 Gait and Exercise Training in Diabetic Peripheral Neuropathy

been noted in ­people with diabetes without measurable neuropathy, but are most
marked in people with moderate–severe diabetic peripheral neuropathy [4]. The causes
of these and other gait alterations are underpinned by the sensory–motor alterations
due to the complications of diabetes and diabetic peripheral neuropathy will be
explained in this chapter.
It may seem surprising given the regularity and automatic nature that this task occurs
within everyday life, but walking is actually a very demanding task from both a physical
and sensory perspective and this becomes very apparent when sensory and motor systems
are impaired by diabetic peripheral neuropathy.

11.3 ­Muscle Forces and the Biomechanics of Gait in Diabetes

The lower limb muscles provide the necessary force to bring about walking and these
­muscles act around our long bones to generate ‘joint torques’ that deliver the rotational
forces required to move the joints, thereby propelling and controlling the body during gait.
In relatively simple terms, it requires a given level of force from the major muscle groups to
walk and this requirement from the muscles increases as the speed of walking increases.
Therefore, by walking more slowly people with diabetes serve to reduce the demands on
their major lower limb muscle groups. This is important since people with diabetes and
particularly those with diabetic peripheral neuropathy have lower muscle strength com-
pared to their non‐diabetic counterparts [6].
Muscle weakness is particularly present in the more distal muscles of the lower limb. The
nature of diabetic peripheral neuropathy intuitively suggests that muscle atrophy will be
greater in the more distal muscles of the lower limb and foot and indeed this has been
shown to be the case [7, 8]. However, more recent research in patients with only mild dia-
betic peripheral neuropathy has shown that it is not only the distal part of the lower limbs
that is affected by muscle weakness in diabetes, but more proximal leg muscles are also
adversely affected compared to age‐matched controls without diabetes [9]. This research
has shown how the ankle plantar flexors (calf muscles) and the knee extensors (front thigh
muscles) are similarly affected by muscle weakness in people with diabetes, being ~30%
weaker than their counterparts without diabetes [9]. This weakness is likely explained not
only though a reduced muscle size, but also through an increased infiltration of non‐con-
tractile intramuscular fat and connective tissue (Figure 11.1). Diabetes itself causes muscle
weakness likely due to the effects of non‐enzymatic glycation acting on the contractile
machinery, but muscle weakness is much more pronounced with the complication of dia-
betic peripheral neuropathy [10, 11].
When walking and undertaking other activities of daily living such as walking up and
down stairs, the level of lower limb strength required for this task can be related to the
maximum strength of those same muscle groups measured using a device known as a
‘dynamometer’ (which tests the maximum strength of a specific muscle group). Using this
approach, it has been shown how patients with diabetes operate much closer to, and even
beyond the limits of their muscle strength capabilities compared to matched controls with-
out diabetes [11, 12]. This is most evident in patients with diabetic peripheral neuropathy
who actually far exceed what their muscles are capable of when measured in isolation on a
 11.3 ­Muscle Forces and the Biomechanics of Gait in Diabete 189

(a) (b)

(c) (d)

Figure 11.1 Representative lower limb magnetic resonance images from a 69-year old control
participant without diabetes (a and c) and a 67-year old patient with diabetic peripheral
neuropathy (b and d). Images are from the mid-thigh level (a and b) and mid-tibia level (c and
d). Grey areas of the image represent skeletal muscle and the white areas subcutaneous fat.
Note: the substantial increase in intramuscular non-contractile material (dark areas inside the
muscle cross-sections are connective tissue) in images from patient with diabetes. Letters in a
and c are abbreviations of muscle names: VL = vastus lateralis, VI = vastus intermedius,
VM = vastus medialis, RF = rectus femoris, BF = biceps femoris, SM = semitendinosus,
ST = semitendinosus, DF = dorsiflexors, SOL = soleus, MG = medial head of the gastrocnemius,
LG = lateral head of the gastrocnemius. The length of the scale-bar along the left side of each
image is 10 cm. Source: Reproduced from: [9].

dynamometer (Figure 11.2). Exceeding maximum muscle capabilities is explained by

­biomechanical differences between the isolated strength test and gait measurements.
Nevertheless, this highlights that patients with diabetic peripheral neuropathy operate at a
much higher proportion of their muscle strength capabilities during everyday tasks and is
likely a critical factor in explaining why patients with diabetic peripheral neuropathy are at
an increased risk of falling. These studies show that people with diabetic peripheral
­neuropathy have very little ‘strength reserves’ available in their muscles to cope with any
unexpected events during gait [11, 12]. For example, if a person tripped during walking,
they would need to produce higher levels of muscle strength in an attempt to try and
recover their balance.
190 11 Gait and Exercise Training in Diabetic Peripheral Neuropathy

(a)
[Flexor (–)/Extensor (+)]

0.5
Hip (Nm/kg)

–0.5

–1

0 10 20 30 40 50 60 70 80 90 100

(b)
1.6 220
[Flexor (–)/Extensor (+)]

Operating strength (%)

Knee Torque (Nm/kg)

1.1 165

0.6 110

0.1 55

–0.4 0
0 10 20 30 40 50 60 70 80 90 100
% of Stance

(c)
1.6 220
*
Ankle Torque (Nm/kg)
[Dorsi (–)/Plantar (+)]

Operating strength (%)

1.1 165

0.6 110

0.1 55

–0.4 0
0 10 20 30 40 50 60 70 80 90 100
% of Stance

Figure 11.2 Joint torque profiles during stance and operating strengths for healthy controls (Ctrl),
diabetic patients with no neuropathy (DM), and diabetic patients with moderate/severe neuropathy
(DPN). Graphs are for (a) hip, (b) knee and (c) ankle joints. Line graphs: joint torque profiles during
stance (mean values for Ctrl-dotted line (n = 27), DM – dashed line (n = 33), DPN – solid line
(n = 20)). Bar chart: operating strength values (mean ± SD values for Ctrl – white (n = 18), DM – black
(n = 27), DPN – grey (n = 14)), shown in the approximate area of stance where peak torque occurred
and from which operating strength was calculated. Significant differences (p < 0.05) from the Ctrl
group for the operating strengths are shown by ‘*’ above the bar. Source: Reproduced from: [11].

11.4 ­Biomechanical Strategies to Alter Gait in Diabetic

Peripheral Neuropathy

Considering the lower limb muscle weakness present in patients with diabetic periph-
eral neuropathy and the importance of adequate lower limb strength production during
gait as discussed above, any method through which the strength required to undertake
daily tasks could be minimized would be very helpful for these patients. A number of
 11.4 ­Biomechanical Strategies to Alter Gait in Diabetic Peripheral Neuropath 191

(a)

(b) (c)

GRF GRF 1 GRF 2

GRF 3

Int MA
Ext MA

Figure 11.3 Definition of internal and external moment arms and illustration of key concepts.
(a) An example sagittal plane magnetic resonance imaging scan of the lower limb showing the
measurement of the internal moment arm length (indicated by the white arrow). (b) Diagram
showing the external moment arm length (Ext MA; black dashed line) as the perpendicular distance
between the resultant GRF vector and the joint centre of rotation (●); the internal Achilles tendon
moment arm (Int MA; red dashed line) as the perpendicular distance between the tendon’s action
line and the ankle joint centre (●). The effective mechanical advantage (EMA) is calculated as:
IntMA/ExtMA. (c) Illustrative example of how the GRF can be applied on the foot in two different
ways causing a reduction in the ExtMA (dashed lines), thereby increasing the EMA and reducing the
ankle joint moment and the muscular force contribution from the plantar flexors: (i) with the point
of application closer to the ankle joint centre (GRF 2 compared to GFR 1) and/or (ii) by an altered
angle of application (GRF 3 compared to GRF 1). Source: Reproduced from: [13].

biomechanical strategies have been observed showing how people with diabetic periph-
eral neuropathy can actually reduce the demands of gait, whether they are conscious
strategies or not.
Walking more slowly as described above is one of the ways in which the strength require-
ments of gait are minimized, but also the shorter steps taken by people with diabetic
peripheral neuropathy serves to reduce the demands on the muscles. Shorter steps involve
less flexion of lower limb joints, which in turn is associated with lower ‘torques’ being
developed around these lower limb joints and a lower strength requirement from the mus-
cles around that joint.
It has recently been shown how patients with diabetic peripheral neuropathy alter the
biomechanics around their ankle joint during walking to minimize the muscle forces
192 11 Gait and Exercise Training in Diabetic Peripheral Neuropathy

from the plantar flexor muscles [13]. During walking, patients with diabetic peripheral
­neuropathy have a smaller ‘external leverage’ around their ankle. This means that they
apply force to the ground through their foot closer towards their ankle compared to
matched controls without diabetes and/or they direct the ground reaction force closer
towards their ankle joint centre (no differences in foot length existed between the
groups). This serves to increase what is known as the ‘effective mechanical advantage’
(EMA) around the ankle and lowers the muscle force requirements from the plantar
flexor muscles (Figure 11.3). All of these biomechanical strategies are helpful for the
patient with diabetic peripheral neuropathy in lowering the demands of walking for
their already weaker lower limb muscles, that are already operating closer to their maxi-
mum capabilities.
The ‘hip strategy’ is another alteration to gait seen in patients with diabetic peripheral
neuropathy. During the ‘push‐off’ phase of walking, the trailing leg is pushed‐off from
the floor and propelled into the ‘swing phase’ to then step out in front of the contralat-
eral leg. This push‐off force comes from the action of the ankle plantar flexor muscles
applying force to plantar flex the foot and provide the necessary propulsion to propel the
leg into the swing phase. Instead of forcefully plantar flexing at the ankle joint, patients
with diabetic peripheral neuropathy tend to ‘drag’ this leg forwards from the hip joint
(hence the term ‘hip strategy’). This strategy makes the hip flexor muscles do the work,
with less reliance on using the ankle plantar flexor muscles [13, 14]. This hip strategy
serves to divert demand for force production during gait away from the weak ankle
­plantar muscles and towards the less affected hip flexor muscles, where more ‘reserve
capacity’ exists.
Walking more slowly lowers the strength demands from the lower limbs as discussed
above. However, a recent study has highlighted that even when walking speeds were
matched between groups, people with diabetic peripheral neuropathy still developed
lower strength at the lower limb joints, explained by the above‐mentioned biomechanical
strategies [15].
Despite altered biomechanical strategies to lower the muscle strength demands of
walking, patients with diabetic peripheral neuropathy use more energy to walk. This
has been shown by measuring the metabolic cost of walking at speeds that are
matched between different groups [15]. Patients with diabetic peripheral neuropathy
had a higher metabolic cost of walking compared to age‐matched controls without
diabetes. This means that they are using more energy to walk at the same speed as
someone without diabetes and this is important because it will make walking feel
more difficult. This may be a reason for patients with diabetic peripheral neuropathy
engaging in less physical activity. Per step, patients with diabetic peripheral neuropa-
thy perform less work with their lower limb muscles, but because they have shorter
strides, they use more steps to walk at the same speed [15]. Cumulatively therefore,
patients with diabetic peripheral neuropathy perform more work with their lower
limb muscles because they need to take more steps compared to controls. This higher
cumulative muscle work is one of the factors believed to contribute to the
higher ­m etabolic cost of walking in people with diabetic peripheral neuropathy.
Other explanatory factors are an increased Achilles tendon stiffness and increased
muscle co‐activation.
 11.6 ­Biomechanical Factors Leading to Increased Fall Ris 193

11.5 ­Falls and Diabetic Peripheral Neuropathy

Falls in the general population are a major problem with one in every three adults over 65 years
falling every year [16]. Such falls are associated with injurious consequences and even an
increased risk of death [17]. People with diabetic peripheral neuropathy are actually up to 20‐
times more likely to fall compared to their aged‐matched counterpart without diabetes [18, 19].
Diabetic peripheral neuropathy is known to be an independent risk factor for falls [18]. Both the
sensory and motor impairments associated with diabetic peripheral neuropathy, together with
the biomechanical alterations to gait contribute to this heightened risk of falling.

11.6 ­Biomechanical Factors Leading to Increased Fall Risk

Weaker muscles and the high demands of gait places patients with diabetic peripheral neu-
ropathy closer to the limits of their muscular capability and therefore at heightened risk of
falling. Certain gait tasks present higher demands compared to normal ‘level’ walking. Walking
up and down stairs is a particularly demanding task from both a sensory and motor point of
view and is one of the most demanding tasks that people perform on a daily basis. These high
sensory and motor demands relate to the fact that the feet need to be placed within a defined
target (the step), which is not the case for normal level ground walking. Any errors in foot
placement may lead to slips, trips, and subsequent falls. Stairs also present increased motor
demands in terms of larger joint ranges of movement and an increased demand for muscle
strength since the body needs to be raised up and lowered down onto the steps [20–22]. These
high demands are underpinned by epidemiology data showing the high incidence of falls on
stairs [23, 24]. The high strength demands of stair walking present a particular difficulty for
patients with diabetic peripheral neuropathy because of weaker lower limb muscles.
It is not only how much strength muscles can produce that is important in moving and
controlling the body during gait, but also how quickly this strength can be developed. This
can be reflected by a measurement known as the speed of strength development, that
reflects how quickly strength in the relevant muscles is produced after the foot contacting
the ground or the step. This is important for controlling and steadying the body upon
ground/step contact and is also known to be an important determinant for recovering from
a trip in older adults [25, 26]. If the speed of strength development is too slow when con-
tacting the ground/step, this may lead to unsteadiness and precipitate a fall. In patients
with diabetic peripheral neuropathy the speed of strength development has been shown to
be slower when walking up and down stairs compared to matched controls without diabe-
tes [27]. Also of particular relevance, is the fact that the demands for rate of strength devel-
opment are higher when walking on the stairs compared to across level ground and
particularly for the ankle plantar flexor muscles when walking down stairs. Taken together
this means that patients with diabetic peripheral neuropathy are slower to generate the
required forces in their muscles to stabilize the body upon ground/step contact and the
very high demands for this on stairs may make this task one of the most dangerous for
patients with diabetic peripheral neuropathy. This impairment in the speed of strength
development in patients with diabetic peripheral neuropathy is one of the major factors
believed to contribute to gait unsteadiness that will be discussed in the following section.
194 11 Gait and Exercise Training in Diabetic Peripheral Neuropathy

11.7 ­Diabetic Peripheral Neuropathy and Balance during Gait

A number of studies have shown how people with diabetes are less able to balance effec-
tively during quiet standing [28]. These studies have measured how much people sway
whilst they are trying to stand still with two feet on the ground. This is typically quantified
by the magnitude of the deviation in the centre of pressure under the feet measured from
force platforms. Although this postural balance task is useful in quantifying static balance
ability, the ‘challenge’ presented by this task is relatively low (with two feet in contact with
the ground) compared to many other daily activities such as walking.
During walking the position of the body’s centre of mass is constantly moving in relation
to the base of support under the feet. This complex task requires the person to not only
propel the body forwards, but also the challenge of doing so safely by maintaining balance.
The challenge to balance presented by walking has been investigated in people with
­diabetes by measuring the separation between the body’s centre of mass and the centre of
pressure under the feet [29]. By necessity during walking, these two points (the centre of
mass and the centre of pressure) will separate and the extent to which they do so fluctuates
as the person moves through the various stages of gait (Figure 11.4). Nevertheless, a greater
separation between the centre of mass and the centre of pressure is regarded as poorer
control of balance and therefore highlighting a person with an increased level of

(a) (b)

Key
CoP position projected vertically

CoM position projected vertically

CoP position

CoM position

CoM-to-CoP separation

Figure 11.4 Graphic illustration of the measurement of the centre of mass to centre of pressure
separation in the anterior–posterior (a) and medio-lateral (b) planes. The body centre of mass
location is projected downwards, and the centre of pressure position under the feet is projected
upwards. Horizontal arrows show the centre-of-mass (CoM) to centre-of-pressure (CoP) separation.
Source: Reproduced from: [29].
 11.7 ­Diabetic Peripheral Neuropathy and Balance during Gai 195

­ nsteadiness. The greater the separation between the centre of mass and the centre of pres-
u
sure, the higher the muscle forces (joint torques) required to maintain balance. If there
comes a point when the centre of mass moves so far away from the centre of pressure,
upright posture can no longer be sustained by the lower limb muscles alone and the person
either falls over, or they need to ‘rescue’ their balance by making another point of contact
with the environment, for example through placing a hand on a wall or handrail. This sepa-
ration between the centre of mass and centre of pressure has been termed ‘dynamic sway’.
Dynamic sway has been measured in people with diabetes whilst walking up and down
stairs as well as across level ground [29]. Patients with diabetic peripheral neuropathy
had a much greater separation between their body centre of mass and centre of pressure
under the feet in the medio‐lateral direction during all activities, meaning that they had
much greater unsteadiness in the side‐to‐side direction, swaying much more than
­controls. Three groups were examined: patients with moderate–severe diabetic periph-
eral neuropathy, patients with diabetes but no neuropathy and matched controls without
diabetes. Interestingly, only the group with diabetic peripheral neuropathy showed this
marked unsteadiness, whereas the group with diabetes but without peripheral ­neuropathy
were very similar to controls without diabetes. Whilst many other aspects of gait ­discussed
above are affected by diabetes even before the onset of diabetic peripheral neuropathy,
this study clearly highlights that the link between diabetes and unsteadiness is a symp-
tom of peripheral neuropathy [29]. The deeper underlying mechanisms to explain why
peripheral neuropathy causes such marked unsteadiness is likely due to both the sensory
and the motor deficiencies associated with diabetic peripheral neuropathy. It seems very
difficult to untangle and dissociate the separate effects of sensory and motor dysfunction
because both aspects are present in patients with diabetic peripheral neuropathy and
may occur simultaneously.
Balance is challenged to the greatest extent when walking down stairs, followed by walk-
ing upstairs, with level walking posing the smallest balance challenge of these three daily
activities. This is highlighted by the highest level of side‐to‐side unsteadiness exhibited by
patients with diabetic peripheral neuropathy when walking downstairs and indicates that
this activity (stair descent) presents the greatest risk for falls with this population [29]. This
is also consistent with the highest demands for rapid speed of strength development when
walking down stairs, particularly from the ankle plantar flexor muscles [27].
A strong positive relationship has been shown between diabetic peripheral neuropathy
and unsteadiness, indicating that as the level of peripheral neuropathy increases, so does
the degree of unsteadiness during walking. Perhaps surprisingly, recent research has high-
lighted a strong positive association between step width and unsteadiness in diabetes, indi-
cating that as the person widens their stance during gait, unsteadiness also increases [29].
A wider step width during gait in people with diabetes has been a consistent finding in the
literature and the traditional interpretation has been that this wider stance provides a wider
base of support and therefore helps to give the person with diabetes more stability. However,
whilst this interpretation is true when two feet are in contact with the ground, walking
involves a cyclical transition between having one and two feet in contact with the ground
at any one time as the person continually steps out placing one foot in front of the other.
During walking, the body centre of mass shifts from side‐to‐side (in the medio‐lateral
plane), to constantly move over the stance foot, cyclically from side to side. Therefore,
196 11 Gait and Exercise Training in Diabetic Peripheral Neuropathy

­ aving a wider step width during walking actually means that the body centre of mass will
h
need to move a greater distance from one side to the other, causing a greater side‐to‐side
sway (dynamic sway) and increasing unsteadiness.
The sensory deficits associated with diabetic peripheral neuropathy undoubtedly play a
major role in gait impairments and unsteadiness leading to falls. For example, the complete
loss of sensation in the foot will lead to delays in the person accurately detecting when their
foot makes contact with the ground/step [27]. This timely understanding of when the foot
comes into contact with the ground/step is important for initiating neuromuscular control
of the limbs and stabilizing the body immediately upon ground/step contact. Indeed, this
time delay in accurately sensing the moment of foot‐ground contact due to diabetic periph-
eral neuropathy is believed to be one of the major factors contributing to the slower speed
of strength development in these patients [27]. Sensory deficits however, may be much less
adaptable to intervention compared to the associated motor deficits. The speed of strength
development, maximum muscle strength and the degree of coordination between different
joints and muscle groups are all realistic targets for exercise intervention that could improve
gait and reduce unsteadiness and this will be discussed in the following sections.

11.8 ­Exercise and Diabetic Peripheral Neuropathy

Participation in physical activity and exercise is much lower in people with diabetes com-
pared to their age‐matched counterparts without diabetes. Whilst this might be one of the
factors involved in the development of type 2 diabetes, physical activity and exercise are
very important for the management of diabetes and minimizing the effects of its complica-
tions. There may be a number of barriers to physical activity and exercise in patients with
diabetes compared to the general population, diabetic foot ulcers being one of the major
issues. Patients with an open diabetic foot ulcer or foot injury should avoid weight‐bearing
physical activity [30]. For patients with diabetic peripheral neuropathy and at high‐risk of
developing a foot ulcer, health professionals may be cautious about recommending weight‐
bearing activity. However, weight‐bearing exercise is not necessarily contraindicated for
patients at high risk of foot ulceration, particularly if appropriate footwear is used and foot
care guidelines followed [31]. Indeed, whilst emphasizing the need for appropriate ­footwear
and daily foot examination by the patient, the most recent American Diabetes Association
guidelines acknowledge that moderate intensity weight‐bearing activity (­walking) does not
necessarily lead to an increased risk for foot ulceration in patients with diabetic peripheral
neuropathy [30]. This guidance is supported by evidence from a number of recent weight‐
bearing exercise studies showing no elevated risk for diabetic foot ulceration with this
increased weight‐bearing activity [31–33].
There are relatively few exercise studies involving people with diabetic peripheral neu-
ropathy [31, 34]. Traditionally ‘aerobic’ type exercise that involves walking on a treadmill
or cycling on a stationary bicycle at moderate intensity has been investigated in patients
with diabetic neuropathy, since this type of exercise can promote improvements in glycae-
mic control. However, more recently, resistance exercise training involving a much higher
intensity, but for a much shorter duration has been successfully applied in patients with
diabetic peripheral neuropathy. This type of exercise is typically performed using machines
 11.9 ­Effects of Exercise in Patients with Diabetic Peripheral Neuropathy on Gait and Balanc 197

where the exercise load can be individually prescribed and selected from a weight‐stack.
The movement typically occurs in a single plane and involves either a single joint (e.g. the
knee joint for the leg extension exercise), or multiple joints (e.g. the hip, knee, and ankle
joints in the case of the leg press exercise). The exercise involves lifting (i.e. a concentric
muscle contraction) and lowering (i.e. an eccentric muscle contraction) a load under con-
trol a number of times, typically for between 6 and 15 repetitions. Each series of repetitions
only lasts for a very short period of time (between ~10–30 seconds) and this is repeated a
number of times interspersed by rest periods, for each muscle group being exercised.

11.9 ­Effects of Exercise in Patients with Diabetic Peripheral

Neuropathy on Gait and Balance

As discussed above, gait and balance are impaired in patients with diabetic peripheral neu-
ropathy and exercise has been applied as a therapeutic strategy with aim of mitigating
many of these aspects. Patients with diabetic peripheral neuropathy walk more slowly and
take shorter strides and exercise has been shown to at least partially mitigate these aspects
by increasing gait velocity and step length [31, 34–36]. Exercise training has also been
shown to increase the capacity of patients with diabetic peripheral neuropathy to under-
take physical activity by increasing the number of steps and distance they are able to walk
[33, 37]. These adaptations were particularly evident in patients taking part in weight‐bear-
ing compared to non‐weight‐bearing exercise, underlining the effectiveness of this type of
exercise [37].
Exercise has been applied in patients with diabetic peripheral neuropathy with the aim
of reducing unsteadiness and the associated risk of falling. A number of studies have
shown improvements in balance after exercise training, although, typically, balance in
these studies has been measured through the assessment of a static postural standing task
[31, 34]. Most studies that have been successful in improving balance and important aspects
of motor function underpinning balance, have used elements of resistance exercise and
balance‐type exercises [35, 36, 38]. Despite patients with diabetic peripheral neuropathy
being affected by motor neuropathy, their motor system remains remarkably adaptable to
exercise. This is supported by a number of studies showing how patients with diabetic
peripheral neuropathy can experience marked gains in muscle strength of up to 65% fol-
lowing resistance exercise training programmes [10]. The fact that patients with diabetic
peripheral neuropathy are capable of increasing muscle strength to such an extent has
important implications for improving gait and balance. As discussed above, patients with
diabetic peripheral neuropathy experience marked muscle weakness and as a result they
operate very close to the limits of their muscular capabilities during everyday tasks such as
walking on stairs and over level ground. An increase in their maximum muscular capabili-
ties through resistance exercise training will have the effect of reducing their level of mus-
cular capability required during daily gait tasks. Essentially, this will allow patients with
diabetic peripheral neuropathy to have a larger ‘reserve capacity’ of muscle strength during
gait. These improved muscular capabilities will enable them to be able to cope better with
the strength demands of gait and have a larger reserve capacity to respond to any ­unexpected
events such as a trip, thereby reducing the risk for falls.
198 11 Gait and Exercise Training in Diabetic Peripheral Neuropathy

As described in the above sections, it is not only the absolute level of muscle strength that
is important for maintaining stability during gait, but also how quickly strength can be
developed in the relevant muscle groups. Resistance exercise training in patients with dia-
betic peripheral neuropathy has been shown to increase the speed of strength development
upon contact with the ground/step during gait by between 27 and 78% [38]. These adapta-
tions in the ankle plantar flexor and knee extensor muscles are believed to translate to
improved balance and stability during gait and reduce the risk for falls.

11.10 ­The Case for Resistance Exercise Training

In the limited literature on exercise for patients with diabetic peripheral neuropathy, resistance
exercise training has been an important element of most if not all studies where improvements to
balance and muscular strength capabilities have been reported [10]. Whilst aerobic‐type exercise
has been acknowledged for conveying benefits for glycaemic control, resistance exercise training
also provides this benefit [10]. This is perhaps intuitive, since skeletal muscle is the largest reser-
voir for glucose in the human body and the effectiveness of resistance ­training for contributing to
improved glycaemic control is another benefit of this type of ­exercise. Also, aerobic‐type exercise
requires patients to exercise for a relatively prolonged duration, albeit at a much lower intensity
compared to resistance exercise training. However, patients with diabetic peripheral neuropathy
transitioning from a relatively sedentary lifestyle to suddenly undertake aerobic‐type exercise with
little prior physical activity/exercise experience, may lack the necessary ‘baseline’ muscular
strength as well as cardiovascular endurance to sustain the requirements of aerobic exercise.
Resistance exercise training might be considered as a good starting point to help patients develop
the necessary baseline muscular strength and endurance to then progress on to some form of
aerobic exercise. Whilst not withstanding some of the potential risks that come with using
­relatively high loads in resistance exercise training, it might ­circumvent some of the associated
risks with aerobic exercise, such as the potential for falls associated with walking activity.
Exercise prescribed in any form should adhere to best practice guidelines, understand
the dose–response relationship and the need for individually tailored exercise programmes
in patients with diabetic peripheral neuropathy [39]. Despite the relative merits and limita-
tions of one form of exercise over another, we still have very limited evidence in patients
with diabetic peripheral neuropathy, but the available evidence is positive in terms of its
effect on improving gait and balance.

­References

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bearing exercise for persons with diabetes and peripheral neuropathy: a randomized
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 201

12

Smart Technology for the Diabetic Foot in Remission

Bijan Najafi1 and David G. Armstrong2
1
Interdisciplinary Consortium for Advanced Motion Performance (iCAMP), Division of Vascular Surgery and Endovascular
Therapy, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA
2
Southwestern Academic Limb Salvage Alliance (SALSA), Department of Surgery, Keck School of Medicine of University of
Southern California, Los Angeles, CA, USA

12.1 ­Background

Diabetes and other non-communicable diseases of decay are now the leading cause of
global mortality in the developed and developing world [1]. Whilst not many people might
realize it, if the diabetes were a country, it would be the third largest in the world with a
population exceeding 425 million (Figure 12.1) [2]. The financial burden of this disease is
also well worth considering, given that the estimated direct annual cost related to diabetes
globally is more than US$ 827 billion [3, 4]. This figure would rank it as 18th amongst the
world’s largest economies [5] (Figure 12.2).
Diabetes foot care costs represent the single largest category of excess medical costs asso-
ciated with diabetes. It is estimated that one-third of all diabetes related costs are spent on
diabetic foot care in United States, with two thirds of these costs incurred in the inpatient
settings, constituting a substantial cost to society [6, 7].
The lifetime incidence of diabetic foot ulcers (DFU) has been estimated to be between
19 and 34% amongst people with diabetes [8]. Ulcers requiring acute care can result in
treatment costs of up to US$28 000 per event, varying with the severity of the wound [9].
Unfortunately, even after the resolution of a foot ulcer, recurrence is common and is
estimated to be 40% within one year after ulcer healing, almost 60% within three years,
and 65% within five years [8]. Perhaps no subsequent complication of DFU is more
­significant than its associated 10–20% rate of lower extremity amputation (LEA)
per event. Indeed, at least 70% of such amputations are potentially preventable [10]. The
consequences of DFU are not limited to amputation. In particular DFUs may put people
at risk for other adverse events such as falls, fractures, reduced mobility, frailty, and mor-
tality [11–13]. For example, mortality after amputation because of diabetes is estimated
to be 70% at five years, which exceeds many common cancers such as breast cancer and
prostate cancer [14].

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
202 12 Smart Technology for the Diabetic Foot in Remission

Millions
1st 2nd

1,387 1,324

3rd
3rd
4th
425
326
262

China India Diabetes United States Indonesia

Figure 12.1 If Diabetes were a country, it would be the world third most populous (International
Diabetes Federation, Diabetes Atlas – 9th Edition http://www.diabetesatlas.org).

US$ billions
14th
1205 15th
16th
1045 17th 18th 18th
932
857 825 19th 20th
770
660 646

Australlia Mexico Indonesia Turkey Diabetes Netherlands Switzerland Saudi Arabia

Figure 12.2 Cost of Diabetes Compared to National Economies. If diabetes were a country, it would
be 18th amongst the world’s top economies with gross domestic product (GDP) of 825 billion per
year. Data Source for the direct cost of diabetes (2017): Harvard T.H. Chan School of Public Health,
https://www.hsph.harvard.edu/news/press-releases/diabetes-cost-825-billion-a-year/. The data
source for GDP was based on World Bank report in 2016.

In light of the impending diabetes epidemic and high provenance of DFU and its associ-
ated complications, the need for enhanced prevention of DFUs is clear. Thanks to new
‘smart’ sensors and communications technology available today, new opportunities have
opened to smartly manage DFUs with personalized screening and timely intervention.
With the help of automation, patients can even be prompted to check their feet, glucose
level, or weight, and enter results into mobile patient portals. Even better: They can trans-
mit the results to their doctors in real time. These fast growing, low cost, and widely avail-
able resources, can help predict one’s risk for foot ulcers, infections, peripheral arterial
disease, frailty, and other diabetes associated complications, ultimately saving limbs and
prolonging lifespan and healthspan.
 12.2 ­Technologies to Guide the Prescription of Footwear-Related Offloading Treatment 203

12.2 ­Technologies to Guide the Prescription of

Footwear-Related Offloading Treatments

Loss of protective sensation [15], impaired blood supply or ischemia accompanying periph-
eral artery disease [16], and abnormal plantar tissue stress (PTS) associated with altered
gait characteristics [17], musculoskeletal foot deformities [18–22], limited joint mobility
[23, 24], and plantar tissue deterioration [18, 25, 26], are key risk factors involved in the
development of foot ulcers. Whilst some of these risk factors such as neuropathy and
peripheral artery disease are hard to be managed, other risk factors such as PTS are man-
ageable and could effectively reduce the risk of DFUs.
PTS is predominantly made up of an interplay of individual mechanical factors: plan-
tar pressure or vertical pressure, shear stress or horizontal pressure, and daily weight
bearing condition (e.g. walking and standing), which defined the frequency of these pres-
sures. Although DFU can form in response to acute trauma such as stepping on a sharp
object, they typically form in response to repetitive stress produced by weight bearing
activity (e.g. walking and standing) conducted by individuals with diabetic peripheral
neuropathy [27]. Reparative stress and shear applied to the surface of the foot as a result
of physical activity could lead to inflammation and eventually damage of the soft tissue,
which is often unnoticed by patients with insensate foot and consequently could lead to
foot ulcer. Similarly, in those with active DFU, excessive foot loading could cause a delay
with healing of DFU because of repetitive moderate stress.
Clinicians and researchers have been
attempting to reduce these mechanical fac-
tors for decades now, to prevent and heal
DFUs. Historically, this was based on sub-
jective clinical judgements to guide ‘off-
loading’ treatments to try and reduce PTS
and in turn prevent or heal DFUs. Recent
advances in wearable technologies now
enable objective assessment of gait abnor-
mality, postural stability, and plantar pres-
sure during routine clinic visit and outside
of a gait laboratory (Figure 12.3). This in
turn may facilitate optimization of offload-
ing prescription. For instance, objective
measurement of plantar pressure in clinic,
could provide immediate verification of
offloading devices to reduce harmful plan-
tar pressure under regions of interest and
if needed to readjust the offloading to max-
imize its efficacy. Recent studies have sug-
gested that these objective measurements
Figure 12.3 Wearable technologies enable
can be used to successfully guide the pre-
measuring gait, balance, and plantar pressure
scription of footwear-related offloading during routine clinic visits and outside of gait
treatments to prevent DFUs [28, 29]. It laboratories.
204 12 Smart Technology for the Diabetic Foot in Remission

could also assist in quick verification of magnitude of alteration in gait and balance because
of offloading and choose a compromised offloading prescription to have sufficient suppres-
sion of harmful plantar pressure with minimum alteration in gait and balance. The latter is
essential to boost adherence to offloading and prevent ­consequence of offloading devices
such as reduction in mobility and falls [30–32].

12.3 ­Technologies to Facilitate Triaging those at High

Risk of DFU
Diabetes requires treatment and everyday preventive strategies to control it. In particular
people with diabetes and loss of protective sensation are faced with the task of continuous
monitoring and managing a number of lifestyle factors including dosage of weight bearing
activities, type of footwear use, and regular screening of feet.
Many health care quality improvement experts recommend improving the process of
high risk foot care through use of stratified foot risk exams [33]. These exams have been
shown to be useful to prevent DFU up to 70% [34], but currently available technologies
remain insufficient to be used on a routine basis by non-expert clinical staff or care givers.
Unfortunately, the reality is that it has been difficult to translate conventional multifacto-
rial risk stratification models from largely private, tertiary care academic centres to com-
munity clinics, which provide care to low-income populations. The centralized centre ‘last
resort’ referral model is also inherently flawed because central multidisciplinary diabetic
foot and wound clinics become easily overloaded when already over-taxed staff and
resources become inundated with critically ill patients. This overflow produces scheduling
backlogs, increases Emergency Department visits and hospitalizations, and leads to
untimely LEA due to lack of coordinated outpatient risk stratification and prevention of
DFU where intervention is likely to be simpler, effective, and low cost. To fill the gap, new
technologies assisting in better risk stratifications without the need of installation of costly
infrastructure or training dedicated staff to use technology and interpret results is desper-
ately needed. This is in particular of key importance for prevention of recurring ulcers.
Unfortunately, caring for the patient in remission following a DFU episode has proven
challenging under standard practice. Numerous prospective studies have explored how
ulcer-free survival is impacted not only by underlying comorbidities, but also by the dura-
tion since the patient most recently healed from a DFU episode [35, 36]. These investiga-
tions suggest that between 30 and 40% of patients experience a recurrent DFU in the year
after healing. Contrast this with the baseline incidence amongst all patients with diabetes,
which has been measured between 3.6 and 5.8% [36]. Thus, a better approach focused on
predicting DFU to enable targeted preventative therapies during this critical period may
significantly improve patient outcomes and reduce DFU-related costs.
Skin temperature measurement and plantar pressure assessments offer objective and
reproducible measurement to identify pathologic processes before they result in ulcers [37].
However, a critical issue in implementing these objective assessments for the purpose of
routine foot screening application is competing comorbidities for consultant time. Besides
clinically based risk classification systems, the addition of sophisticated gait lab measures
(e.g. plantar foot pressure and thermometry) have been identified as high-leverage areas for
 12.3 ­Technologies to Facilitate Triaging those at High Risk of DF 205

Textile-based sensors to
monitor plantar pressure Inertial sensor to monitor physical activities

Figure 12.4 Sensoria Socks (Sensoria Inc., Redmond, WA, USA) which enables monitoring plantar
pressure under three plantar regions of interest including heel, first metatarsal head, and fifth
metatarsal head. In addition, it includes a three axial inertial sensor attached on shin which may be
used for monitoring daily physical activities.

DFU prevention [38–42]. At first glance, the practicality of using these measures under the
current constraints of the US health care delivery system appears ambitious at best.
Recently, new technologies have been developed to address the limitation of previous
methods of assessing risk factors associated with DFU. In particular, new features such as
real-time estimation of risk factors, using telecommunication means such as smartphone
and smartwatch to interact with users and/or caregivers/care providers, and enhancing
form factors to improve the level of comfort as well as daily use capability (e.g. using highly
flexible sensors, smart textile, etc.) were added to improve ease of measurement of DFU
risk factors for the purpose of daily foot monitoring. In 2017, Raviglione et al. [43], pro-
posed the concept of daily monitoring of plantar pressure in people at risk of DFU using a
smart textile (Sensoria socks, Sensoria Inc., Redmond, WA, USA, Figure 12.4). Their
system contained a textile pressure sensor attached to a stretchable band, hardware
that collects data and transmits them via Bluetooth to a phone, an app that gathers the data
and stores them in the cloud, and a web dashboard that displays the data to the clinician.
Their study was however limited to in vitro testing. Other developed wearable technolo-
gies claiming to be capable of measuring plantar pressure using thin or highly flexible
sensors and identified by our systematic search are Walking Sense® proposed by Deschamps
and Messier in 2015 [44]; smart shoes based on a microstrip patch antenna and able to
measure pressure and horizontal force (shear) proposed by Sheibani and colleagues in
2014 [45]; a multiplexed inductive force sensor which enables measuring plantar pres-
sure and shear forces distribution proposed by Du et al. in 2015 [46]; a highly flexible
pressure-measuring system based on Fibre Bragg Grating (FBG) and the lead zirconate
titanate (PZT) piezoceramic sensors, proposed by Suresh et al. in 2015 [47], which enables
measuring plantar pressure during walking at low and high speeds; Sawacha [48] and
Ferber et al. suggested an in-shoe plantar sensory replacement unit to provide alert-based
feedback derived from analyzing plantar pressure threshold measurement in real-time;
Dabiri et al. [49] suggested an electronic orthotic shoe which enables the monitoring of
foot motion and pressure distribution beneath the feet in real time and of providing
continuous feedback (via a text message to the patient and the patient’s caregiver) in the
case where an undesired behaviour was detected; a similar concept was proposed by
206 12 Smart Technology for the Diabetic Foot in Remission

Femery et al. [50] in which a biofeedback device (auditory and visual signals) was used to
notify excessive, insufficient, or correct foot offloading. However, all of these studies were
conducted in vitro or using healthy subjects, thus their capability to predict or prevent DFU
still needs to be examined.
In addition to the measurement of plantar pressure, several technologies have been
designed to identify pre-ulceration damage to the plantar tissue of the feet via the assess-
ment of plantar temperature [39, 41, 51, 52] or the assessment of thermal stress response
(TSR) [53, 54]. The rational for measuring plantar temperature is built on the notion that
the foot heats up before it breaks down into ulcers. The isolated plantar regions with
increased heat are mainly due to inflammation response of near damaged or damaged tis-
sue and originally was suggested by Paul Brand and his team in 1975 as an effective method
to predict foot ulcer prior skin breakdown [55]. Almost two decades later in 1997,
Armstrong, Lavery, and their colleagues [51] have proposed the use of a portable hand-
held infrared skin temperature probe as an effective technique to predict foot injury as well
as foot complications because of Charcot’s arthropathy. Later on, in 2007, Lavery et al. [41]
suggested that using thermography as a self-assessment tool is effective to prevent recur-
rence of DFU. In their study, physician-blinded, randomized, 15-month, multicentre trial
was designed in which 172 subjects with a previous history of diabetic foot ulceration were
assigned to standard therapy, structured foot examination, or enhanced therapy groups.
Each group received therapeutic footwear, diabetic foot education, and regular foot care.
Subjects in the structured foot examination group performed a structured foot inspection
daily and recorded their findings in a logbook. If standard therapy or structured foot exam-
inations identified any foot abnormalities, subjects were instructed to contact the study
nurse immediately. Subjects in the enhanced therapy group used an infrared skin ther-
mometer to measure temperatures on six foot sites each day. Temperature differences
>4 °F (>2.2 °C) between left and right corresponding sites triggered patients to contact the
study nurse and reduce activity until temperatures normalized. Their results revealed that
patients in the standard therapy and structured foot examination groups were 4.37 and
4.71 times more likely to develop ulcers than patients in the enhanced therapy group.
Thus, the study concluded that home monitoring of plantar temperature assessment is a
simple and useful tool for prevention of recurrence of ulcers. In 2014, van Netten et al. [56]
reconfirmed the value of skin temperature assessment for prediction of DFU. They moni-
tored plantar skin temperature using an infrared camera in 54 patients with diabetes visit-
ing the outpatient foot clinic. Nine (17%) patients had complications requiring immediate
treatment, 25 (46%) patients had complications requiring non-immediate treatment, and
20 (37%) patients had no complications requiring treatment. They have suggested a 2.2 °C
difference between contralateral spots could discriminate cases with urgent care need
with sensitivity and specificity of 76%, and 40%, respectively. Using a cut off of 1.35 °C
could improve sensitivity to 89% and specificity to 78%. Despite these studies and clear
evidence on the benefits of plantar temperature assessment, to date, plantar temperature
monitoring is still not part of standard of care and/or preventive care for managing the
diabetic foot. This could be partially because of the form factor of initial thermography
tool, which is dependent on patient adherence in daily use of handheld thermography as
well as their ability to perform the test, see the visualized temperature, and the ability to
interpret the temperature difference (e.g., only the difference between two identical spots
 12.3 ­Technologies to Facilitate Triaging those at High Risk of DF 207

17°C 20°C
A typical case with asymmetry of
plantar temperature captured by the mat
Figure 12.5 Podimetrics Mat (Podimetrics Mat, MA, USA) enables predicting foot ulceration by
facilitating home measurement of plantar temperature. The present algorithm can now identify
people with 97% accuracy and an average lead time of 37 days [57].

from left and right feet beyond of approximately 2.2°C is clinically meaningful). Almost
two decades later in 2017, Frykberg et al. [57] proposed a smart mat based on the tele-
health concept, which could address the limitations of previous thermography tools.
Specifically, they studied a novel in-home connected foot mat (Podimetrics Mat™, MA,
USA, Figure 12.5) to predict the risk of DFU and better stratify those who need an urgent
foot care. This simple-to-use system was designed to require no configuration or setup by
the users who simply had to step on the mat with both feet for 20 seconds. The system then
compared the temperature profile of the two feet. Using a threshold of 2.22 °C difference
between corresponding sites on opposite feet, the mat correctly predicted 97% of DFUs
with an average lead time of 37 days. Adherence to the mat was high with 86% of partici-
pants using the mat at least three times per week, and average use was five times per week.
Whilst this accuracy and 37 days lead time could be sufficient to better target those who
need urgent care, the technology still suffers from an important limitation. The threshold
of 2.22 °C, which provided 97% sensitivity, yielded only 43% specificity. Increasing the
threshold value increases specificity but decreases sensitivity. Under the standard inter-
vention paradigm for monitoring temperatures of the feet, false positives would result in a
user being unnecessarily advised to reduce their physical activity level or overwhelm the
podiatry clinic with unnecessary patient visits.
Whilst the Podimetrics mat enables the daily monitoring of plantar temperature, it
provides however a snapshot of plantar temperature irrespective of daily physical activi-
ties. Whilst a single snapshot of temperature could be sufficient to determine the sign of
inflammation before breakdown of skin or foot ulcers, continuous monitoring of plantar
temperature could provide additional information, which also may be useful for reduc-
ing false positives, increasing sensitivity, and monitoring other risk factors like shear
stress [53, 54, 58]. In an effort to address this limitation, Najafi et al. [58] studied a smart-
textile device (SmartSox, Novinoor LLC, IL, USA, Figure 12.6), which enable simultane-
ous and continuous measurement of plantar temperature, pressure, and joint angles by
measuring changes in light wavelengths circulating in a thin and highly flexible fibre optic
weaved in a standard sock. To demonstrate the validity of this device and determine
risk factors associated with DFU, they have recruited 33 patients with diabetes and neu-
ropathy from an outpatient podiatry clinic. All participants were asked to walk a distance
208 12 Smart Technology for the Diabetic Foot in Remission

Figure 12.6 SmartSox (Novinoor LLC, IL, USA) is a smart textile device based on fibre optics
enables simultaneous and continuous measurement of plantar pressure, plantar temperature and
lower extremities joint angles (e.g. hallux flexion-extension).

of 20 m with their regular shoes at their habitual speed whilst wearing a pair of SmartSox.
To validate the device, results from TSR [53, 54] using thermography and peak pressure
measured by computerized pressure insoles (F-scan, TekScan, MA, USA) were used as
gold standards. They reported a significant correlation for pressure profile under different
anatomical regions of interest between SmartSox and F-scan (r = 0.67, p < 0.050) as well as
between thermography and SmartSox (r = 0.55, p < 0.050). In laboratory- controlled condi-
tions, the agreements for parameters of interest were excellent (r > 0.98, p = 0.000) and no
noticeable contradiction between measurements of temperature, angle, and pressure was
observed. Whilst, their results are promising and their proposed form factor (using socks
instead of insoles) enables monitoring major biomechanical risk factors associated with
DFU irrespective of type of footwear including sandals, offloading, and shoes, it is still
unclear whether the proposed measurements are sensitive enough to predict DFU and
whether simultaneous measurements of temperature, pressure, and lower extremity joints
angles could reduce false prediction of DFU. The technology is however not suitable for home
 12.3 ­Technologies to Facilitate Triaging those at High Risk of DF 209

Figure 12.7 Siren Socks enables continuous home temperature monitoring, which may be used as
an early warning system, to provide people with objective feedback so they can modify their
activity and protect their foot before ulcers develop.

assessment since associated electronics including laser light amplifier are bulky and power
consuming, thus unsuitable for long term remote monitoring including home applications.
In 2018, Reyzelman and co-workers proposed a simpler solution, which could be more
appropriate for continuous monitoring of plantar temperature at home and during daily
physical activities. The technology called Siren Socks (Siren Diabetic Socks, Neurofabric,
Siren Care Inc., San Francisco, CA, Figure 12.7) are made of smart textile with microsen-
sors woven into fabric of socks. These virtually invisible sensors are seamlessly integrated
into the socks to monitor temperature changes on the bottom of the feet and under five
plantar regions of interest including hallux, metatarsal points 1, 3, and 5, midfoot, and
heel. The sensor-embedded socks are designed to be reusable and are machine washable
and dryable. The device also enables recording lower extremities motion thanks to its tri-
axial inertial sensor integrated in the sock. Using a mobile application, the plantar tem-
perature could be visualized on a daily basis. A warning sign is generated based on
changes in the pattern of plantar temperature. The socks are wirelessly connected with the
mobile phone via Bluetooth. In a pilot study, authors examined accuracy of the device in
35 people with DPN within three groups: Group 1 included subjects with DPN and no
210 12 Smart Technology for the Diabetic Foot in Remission

previous history of ulcers (n = 11); Group 2 included subjects with DPN and a previous
history of ulcers (n = 13); and Group 3 included subjects with DPN and a current pre-ulcer
as determined by the investigators (n = 11). Participants were provided with the socks and
were given an Android mobile phone with the app needed for temperature monitoring.
They were instructed to wear the socks continuously for six hours, after which the socks
could be removed. The recording was continued for seven days plus or minus two days.
Participants were then requested to grade their experience including usability of the sen-
sor-embedded socks using a questionnaire. Before implementation, the measured temper-
ature by socks were compared to the reference standard, a high-precision thermostatic
water bath in the range 20–40 °C. Their results suggest that the temperatures measured by
the sensors woven into the socks were within 0.2 °C of the reference standard with high
agreement with the reference system, when the temperature changed between 20 and
40 °C. Patients reported that the socks were easy to use and comfortable, ranking them at
a median score of 9 or 10 for comfort and ease of use on a 10-point scale. This study was
however limited to feasibility study, and accuracy of the socks to predict foot ulcers needs
to be validated in future studies.
There are also a number of technologies that enable temperature measurement between
insole and shoes, which may also assist in the prevention of DFU by indirect measurement
of shear stress and generated sweating during daily physical activities. In 2016, Sandoval-
Palomares and colleagues [59], suggested a continuous monitoring portable device that
monitors the micro-climate temperature and humidity of areas between the insole and sole
of the footwear. The monitoring system consisted of an array of 10 sensors that take read-
ings of relative humidity within the range of 100% ± 2% and temperature within the range
of −40 to 123.8 ± 0.3 °C. For assessment of their study, two healthy subjects were recruited
and were asked to wear a pair of insoles with 1 cm of thickness, which included five sensors
integrated in circular holes. The holes created an air channel of microclimate area between
the plantar surface-insole and the sensor, which enables reading the plantar surface tem-
perature and humidity data. They have been able to continuously monitor temperature and
humidity data without any technical difficulties. However, no gold standard was used to
examine the accuracy of reading.
Shear stress is another important risk factor associated with DFU, which was hard to
measure until recently [37]. DFU may occur at locations of hyperkeratosis tissue, which
itself is caused by friction (shear) on the foot [60]. Yavuz et al. [61] suggested that in 60% of
subjects with DPN, peak shear, and peak pressure sites are different and ulcers were often
occurring at peak shear only locations, not overlapping with peak pressure location. Most of
the technologies for assessing shear were based on discrete tri-axial force transducers in the
shoes or purpose-built platforms with an array of small force sensors as discussed in the
­section of plantar pressure assessments. However, recently some researchers suggested
assessing TSR as a surrogate to measure shear force. This idea was first introduced in 2012 by
Najafi et al. [53] in which changes in plantar temperature in response to 50 and 150 steps
were examined in 15 individuals with Acute Charcot neuroarthropathy (CN) and 17 non-CN
participants with type 2 diabetes and peripheral neuropathy. Their results suggest that vari-
ability in thermal response to the graduated walking activity is a useful metric to discrimi-
nate high risk patients and could provide further insight into the correlation between thermal
response and ulcer/Charcot development. Later in 2014, Yavuz et al. [62] ­demonstrated an
 12.4 ­Technologies to Manage Dose of Physical Activities in People with Diabetes and Insensate Foo 211

association between TSR and shear force. They recruited 13 healthy ­subjects and monitored
plantar temperature using a thermal camera pre and after 10 minutes walking on a treadmill.
As a reference system, they used a custom-built stress plate, which enables measuring
­plantar triaxial stresses. The results suggested a relatively high correlation (r = 0.78) between
peak shear stress and temperature increase in response to 10 minutes treadmill walking. The
correlation was weaker between a change in temperature and peak pressure (r = 0.46),
­suggesting that TSR is mainly as a result of shear stress. A few other studies have also
­indirectly linked the association between TSR and shear stress.
In 2014 Wrobel et al. [63] examined the effect of a shear-reducing insole on the TSR.
Twenty-seven diabetes peripheral neuropathy patients were enrolled and asked to take 200
steps in both intervention (walking with shear reducing insoles) and standard insoles (walk-
ing with similar insoles without shear reducing component). Using thermography, changes
in plantar temperature in response to 200 steps walking were measured. After walking in
both insole conditions, foot temperatures increased significantly in standard insoles.
However, the shear reducing insoles significantly reduced forefoot and midfoot temperature
increases, compared to standard insoles on average by 64% and 48%, respectively.
In 2017, Rahemi et al. [53], tested the impact of shoe closure on plantar TSR. Fifteen
eligible subjects were enrolled. The left foot was used as a reference and fitted to a self-
adjusted and habitual lace-tightening method by each subject. The right foot was used as a
test closure and fitted into three lace closure conditions: loose, tight, and preset optimal
closure (reel clutch, BOA technology). Whilst, it could be assumed that walking condition
was identical between right and left foot, the TSR for the right foot, when the shoelace was
loosed was significantly higher on average by 70% compared to the left foot, which shoe
lace was tightened appropriately. This increase in temperature in the side with loose shoe-
lace was linked with higher shear stress. They results however have suggested that making
shoelace too tight will also increase TSR on average by 67%. The authors speculated that
poor skin perfusion because of too tight shoelaces, may reduce foot acclimatization and
thus contribute to increasing plantar temperature. Therefore, TSR is not only in response to
shear stress but also could be in response to poor skin perfusion.

12.4 ­Technologies to Manage Dose of Physical Activities

in People with Diabetes and Insensate Foot

Identification of specific thresholds for volume of foot stress (e.g. daily number of steps or
time spent in standing) that the diabetic foot can tolerate is poorly understood [12, 64].
Repetitive pressure and shear stress applied to the surface of the foot as a result of physical
activity could lead to inflammation and eventually damage of the soft tissue, which is often
unnoticed by patients with insensate foot and consequently could lead to foot ulcer. Similarly,
in those with active DFU, excessive foot loading could cause a delay with healing of DFU
because of repetitive moderate stress. Therefore, clinicians are often cautious about advising
extra activity to their patients with DFU or at risk of DFU [12]. However, several studies
have shown that the individuals that ulcerated had lower physical activity levels than those
that did not ulcerate [65, 66]. Furthermore, whilst walking on an unprotected wound may
be plausibly detrimental to healing, the role of exercise and daily physical ­activities on
212 12 Smart Technology for the Diabetic Foot in Remission

health benefits cannot be ignored, even in patients with DFU. On the other hand, prolong
immobilization of foot may lead to deconditioning, muscle atrophy and weakness increas-
ing likelihood of frailty and long-term complication for patients [12, 67, 68].
Armstrong and Boulton [69] suggested that it might be possible to prescribe physical
activity ‘dosages’ to at-risk patients. Whilst standardized physical activity recommenda-
tions to reduce DFU risk that are based on cumulative tissue stress remain elusive due to
individual differences in stress tolerance, there are opportunities to incorporate technolo-
gies into offloading footwear to monitor and/or prescribe personalized modifications to
physical activity [64, 68, 70, 71]. Efforts are currently underway to commercialize smart
footwear with capability of real-time plantar pressure screening (smart insoles or smart
textile) during both static (e.g. standing or sustained pressure) [71] and dynamic (e.g.
walking) [43, 72] stress applied to the feet and providing this information to both patients
and care providers. Some recent efforts have also added a real-time feedback from plantar
pressure during activities of daily living that could notify patients about harmful activities.
For instance, Raviglione and colleagues [43], introduced a smart textile-based system
(Sensoria Inc., Redmond, WA, USA, Figure 12.4) capable of continuously measuring the
pressure and notified high pressure instance via a smartphone. They concluded that this
technology could determine optimal off-loading in the community setting and assist with
prevention of DFU. However, their study was limited to a proof of concept design and no
clinical study was conducted to support the conclusion. In another effort, Najafi et al. [71]
introduced smart insoles to prevent recurrence of ulcers. In their study, 17 patients in dia-
betic foot remission (history of neuropathic ulceration) were instructed to wear a smart
insole system (the SurroSense Rx, Orpyx Medical Technologies Inc., Calgary, Canada,
Figure 12.8) over a three-month period. This device is designed to cue offloading to manage

Smart Insoles to screen sustained Smart watch to assist patients to avoid physical
plantar pressure (15 min or longer) activities (e.g. prolong standing) leading to sustained
plantar pressure

Figure 12.8 Recent advances in wearables enables providing timely and real-time feedback to
patients to protect their feet against conditions that may increase risk of diabetic foot ulcer. The
SurroSense Rx (Orpyx Medical Technologies Inc., Calgary, Canada) is an example of such
technologies that enables continuous screening plantar pressure through smart insoles and
notifying the patient in case of a sustained plantar pressure beyond a pre-defined threshold was
observed. This technology could be used to educate patient to avoid conditions leading to
sustained plantar pressure (e.g. unbroken and prolonged standing), which in turn could assist with
prevention of diabetic foot ulcers.
 12.4 ­Technologies to Manage Dose of Physical Activities in People with Diabetes and Insensate Foo 213

unprotected sustained plantar pressures in an effort to prevent foot ulceration. The focus of
this study was mainly towards the activities that could generate sustained (e.g. greater than
15 minutes) but not necessary high pressure such as foot loading during sitting and stand-
ing, which could be caused by inappropriate footwear, foreign objects inside of shoes, pres-
ence of callus, or prolonged standing. A successful response to an alert was defined as
pressure offloading, which occurred within 20 minutes of the alert onset. Patient adher-
ence, defined as daily hours of device wear, was determined using sensor data and patient
questionnaires. Changes in these parameters were assessed monthly. Whilst no reoccur-
rence of ulcers was observed in their study, which may suggest that the system was effective
to prevent reoccurrence of study, the results need to be confirmed in a level one evidence
with larger sample size and over ample period of follow up (e.g. one year). However, an
interesting observation in this study is the benefit of real-time alert to improve patient
engagement and adherence to prescribed footwear. Specifically, they found out that ­alerting
patients at least once every two hours could significantly improve adherence to prescribed
footwear over time.
In addition, some recent researches postulated harmful physical activities that
could increase the likelihood of foot ulcers. For example, a 2010 study by Najafi et al.
[73] found that patients at risk of DFU spent three times longer on standing posture
compared to walking. Standing period, often neglected in previous studies focused on
managing plantar pressure [12], could be even more risky than walking in people
with risk of DFU because of reduced hyperemic response under the diabetic neuro-
pathic foot [37]. Newrick and colleagues [74] have demonstrated that the time for
blood flow return to baseline (resting flow) following three minutes standing is almost
twice as long in neuropaths compared to healthy subjects, which could lead to local
ischemia and development of callus and consequently an ulcer. Thus, it could be pos-
tulated that a prolonged standing period (e.g. longer than three minutes) could be
harmful for neuropathic patients and should be avoided. This threshold could be used
by new interactive technologies to alert patients when such harmful activities has be
occurred.
Armstrong et al. [75] has revealed another potential harmful activity behaviour, which
could increase risk of DFU. The group utilized computerized activity monitors to prospec-
tively monitor the physical activity patterns of 100 patients at risk of DFU. They revealed
that those who ulcerated had lower average daily activity levels as well as greater day-to-
day variability in their activity level. Based on these studies, in a review paper, Crews et al.
[64] concluded that low physical activity levels paired with ‘periodic bursts’ in activity
could lead to DFU formation. To reach this conclusion, they drew inspiration from the
­tissue stress theory suggested by Kluding et al. [76] in which it was suggested that the skin
and soft tissue of the feet develop ‘decreased stress tolerance’ in individuals at risk of DFU
who maintain low daily activity levels. Thus, when those individuals subsequently have a
spike in activity (increased variability), their foot is unable to tolerate the increased stress
and a DFU forms. In contrast, individuals who maintain consistently higher levels of phys-
ical activity have tissue that is conditioned to tolerate a higher level of stress. Under the
theory, individuals who gradually increase their physical activity should benefit from grad-
ually increased stress tolerance. However, individuals who excessively exceed their normal
physical stress levels will encounter tissue injury or death. Smart shoes, smart insoles,
214 12 Smart Technology for the Diabetic Foot in Remission

smart socks, or new generation of activity monitoring could assist patients with DFU to
maintain a steady activity patterns and avoid an activity burst, which may increase risk of
DFU formation.
Management of dose of activities, when patients have active foot ulcers could be also
important to avoid delay in wound healing. However, the current literatures are unclear on
this topic. Conventional wisdom dictates that once an individual exceeds their tissue’s tol-
erance level and develops a DFU, they should limit activity as much as possible to allow the
DFU to heal. However, Vileikyte et al. [77] found that daily step count and offloading
adherence level were each positively associated with wound healing in subjects with DFU,
whilst the adherence was stronger predictor of wound healing. This observation is contra-
dictory with observation in Najafi et al., in which 49 patients with active DFU was rand-
omized to receive either a removable cast walker (RCW: with uncertain adherence to
offloading during everyday activities) or the same cast walker rendered irremovable (iTCC:
with 100% adherence to offloading during day and night time) for the offloading of their
wounds. They found negative associations between daily number of taken steps and speed
of weekly wound healing irrespective of level of adherence to offloading (RCW or iTCC).
They have also reported that the association between low pressure activities (e.g. standing)
and speed of wound healing is highly depending on the type of offloading. For instance,
those who are using RCW with uncertainly in adherence, a relatively high negative correla-
tion (r = −0.60) was observed between duration of standing and weekly speed of wound
healing. However, in those who are using iTCC, which reinforced adherence during day
and night, no correlation was found between standing and wound healing speed.
Interestingly, when they look at the success of wound healing at 12 weeks in a multiple
variable model, only standing duration, type of offloading, and initial wound size were
intendent predictors of success of wound healing, suggesting the importance of managing
prolonged and unbroken standing bouts irrespective of type of offloading.

12.5 ­Using Technology to Improve Patient Education

for Effective Prevention of Diabetic Foot Ulcers

Disease education with patients at risk of DFU is a long advocated component of DFU
prevention and critical intervention to benefit outcomes [78]. The role of ulcer prevention
education is of particular importance for the prevention of ulcer recurrence immediately
after healing of the ulcer, in whom the recurrence rates is estimated to be approximately
40% during the first year [8]. Several reviews and systematic reviews have provided evi-
dence for the effectiveness of diabetic education programmes in reducing diabetic foot
ulceration, amputation, and generate cost-effective reduction in lower extremity complica-
tions [78–81].
One of the important component of any patient education programmes for prevention of
DFU is patient adherence to diabetic footwear designed for improving wound healing and/
or prevention of DFU. Clinical care for diabetic ulceration focuses on external offloading of
the foot or shifting plantar pressure during gait from the wound area to an unaffected area.
However, clinical footwear trials are equivocal and approximately 40% of these patients
still re-ulcerate within one year [8]. A lack of adherence leads to the majority of these
 12.6 ­Mobile Health (mHealth) to Manage Diabetic Foot Ulcer 215

r­ e-ulcerations. Specifically, despite taking over 50% of their steps at home, patients view
their home as a ‘safe zone’ where they do not feel the need to wear their prescribed foot-
wear [82]. As a result, high-risk patients wear their prescribed footwear only 15–28% of the
time. Advances in technology allows for the implementation of a timely alert, notification,
or auto-reminder programme to improve adherence.
In 2017, Najafi et al. [71] tested the effectiveness of a real-time alerting system to improve
adherence to predicted diabetic shoes over time. They recruited 17 patients in diabetic foot
remission (history of neuropathic ulceration). Participants were asked to wear a pair of
diabetic shoes equipment with a thin (<0.5 mm) smart insole system (the SurroSense Rx,
Orpyx Medical Technologies Inc., Calgary, Canada, Figure 12.8) on a daily basis over a
three-month period. This device is designed to cue in real-time unprotected sustained plan-
tar pressures (continuous pressure above 35 mmHg for more than 15-minute). A smart-
watch was used to notify in real-time detected sustained pressure. The feedback was
provided via watch vibration as well as visual indication of high pressure plantar spots
(with red colour) via colourful interface of the smartwatch. Adherence was defined by daily
hours of device wear measured objectively by the system. Overall daily adherence was aver-
aged on a monthly basis. They reported that those who received at least one alert every two
hours had significant improvement in adherence in the month 3 compared to the first
month of monitoring. In addition, those who received frequent alerts, improved their suc-
cess of response to alert, which was defined as successful offloading within 20 minutes of
the alert onset. They concluded that a real-time and comprehensive alert method with a
minimum number of alerts (one every two hours) are effective to optimally respond to
offloading cues from a smart insole system and improving adherence to prescribed diabetic
shoes over time.

12.6 ­Mobile Health (mHealth) to Manage Diabetic Foot Ulcers

Cell phones and other consumer digital technologies have emerged as potentially powerful
tools to empower patients to take care of their own chronic condition from accurate diag-
nosis to patient education, engaging them in their own care, monitoring the risk of DFU,
and determining any complication associated with wound healing. However, many of
these technologies are still in infancy stage. In 2015, Parmanto et al. [83] proposed a mobile
app to support self-skincare tasks, skin condition monitoring, adherence to self-care regi-
mens, skincare consultation, and secure two-way communications between patients and
clinicians. The system may help in supporting self-care and adherence to care manage-
ment, whilst facilitating communication between patients and clinicians. Wang et al. [84]
developed an app for analysing wound images. The developed app enables capturing
wound image with the assistance of an image capture box. The software allows detecting
wound boundary and determine healing status. Mammas et al. [85] proposed the smart
phone as a mobile-telemedicine platform. They evaluated the feasibility and reliability of
the platform based on simulating experimentation by 10 specialists, who remotely exam-
ined a diabetic foot using the proposed mobile platform. They demonstrated that this plat-
form allows remote classification of the wound as well as the risk of amputation with
accuracy of 89% on average. In addition, the acceptability of the platform was in range of
216 12 Smart Technology for the Diabetic Foot in Remission

89–100% amongst specialists. A similar concept was proposed by Foltynski et al. [86] in
which an app was designed to measure wound area and sends the data to a clinical data-
base and creates a graph of the wound area change over time. The team has also suggested
an elliptical method [87] to improve wound size estimation from 16 different wound shape.
Sanger et al. [88] proposed a mobile app to engage patients in wound tracking, which in
turn could assist in identifying wound infection. However, their study was limited to design
concept with no clinical study. An interesting application of mHealth was proposed by
Quinn et al. [89] to improve patient referral strategy from tertiary centres. Specifically, they
proposed utilizing mobile phone technology to decentralize care from tertiary centres to
the community, improving efficiency and patient satisfaction, whilst maintaining patient
safety. Their designed app enables remote collection of patient wound images prospectively
and their transmission with clinical queries, from the primary healthcare team to the ter-
tiary centre. They tested this platform in five public health nurses in geographically remote
areas of the region. They demonstrated that images could be transmitted securely, is safe
and reliable and could be used for remote wound bed assessment and determine skin integ-
rity/colour. They concluded that with minor adjustments, this application could be used
across the community to reduce patient attendances at vascular outpatient clinics whilst
still maintaining active tertiary specialist input to their care.

12.7 ­Internet of Things and Remote Management

of Diabetic Foot Ulcers

One of the fast developing infrastructures promising to revolutionize the diabetic foot care
industry is the Internet of Things (IoT) [90]. It is expected that 50% of healthcare over the
next few years will be delivered through virtual platforms. This has accelerated develop-
ment of a new market named ‘digital wellness’, which combines digital technology and
health care [90]. Digital technology-based health care is regarded as a natural and ultimate
choice for remote, home-based, and long-term care of patients with chronic conditions due
to its low cost, high accuracy, and continuous monitoring and tracking capabilities. IoT
involves a system of devices, machines, or anything with the ability to transfer data without
the need for a human to implement the communication [91]. Fueled by the recent adapta-
tion of a variety of enabling wireless technologies such as RFID tags and wearable sensor
and actuator nodes, the IoT has stepped out of its infancy and is the next revolutionary
technology in transforming the Internet into a fully integrated ‘Future Internet’ [91]. As we
move from www (static pages web) to web2 (social networking web) to web3 (ubiquitous
computing web), the need for data-on-demand using sophisticated intuitive queries
increases significantly. What has made IoT the next big thing is not just its machine-to-
machine component, but the potential of sensor-to-machine interaction. With the increas-
ing development of health sensors, there is a growing opportunity to utilize IoT for medical
data collection and analysis. It is expected that integration of these tools into the healthcare
model has the potential of lowering annual costs of chronic disease management by close
to one-third [92]. The use of IoT for medical applications and is however still in infancy. In
particular, our systematic search didn’t identify any study related to application of IOT for
management of DFUs. But significant business decisions have been taken recently by
major information and communication technology (ICT) players like Google, Apple, Cisco,
 12.8 ­Technologies to Facilitate Delivering of Therapy at Home and Reduce Risk of DF 217

and Amazon to position themselves in the IoT landscape. For example, in 2014 Novartis is
working with Google on sensor-technologies, such as the smart lens, and a wearable device
to measure blood glucose levels [93]. In 2017, Amazon teamed up with Merck and Luminary
Labs on an effort called the Alexa Diabetes Challenge, with the goal of finding the ultimate
way to monitor diabetes using voice-enabled solutions [94]. As the IoT continuous to
develop, further potential is estimated to develop to facilitate management of chronic con-
ditions at home including effective and timely management of diabetic foot at risk as well
as facilitating the delivery of care for speed up wound healing.

12.8 ­Technologies to Facilitate Delivering of Therapy at

Home and Reduce Risk of DFU

Wearable technologies are not limited to monitoring. These technologies also enable daily
intervention outside of clinic [95]. For instance, few studies have suggested that delivering
regular electrical stimulation or pulsed radio frequency energy via wearable technologies
could be potentially effective to prevent DFU, reduce risk factors associated with DFU, or
speed up wound healing [95–98]. In 2017, Najafi et al. [99] have demonstrated that daily
home use of wearable technology that enables delivery electrical stimulation under plantar
regions of interest (e.g. forefoot and hind foot, Figure 12.9) is feasible, highly acceptable,
and effective to improve plantar sensation as quantified by vibratory plantar threshold
(VPT) amongst people with diabetes and loss of plantar protective sensation. In addition,
their study suggests that vascular health could be improved in the subgroup with high
ankle brachial index (ABI > 1.20). Other significant improvements observed compared to

Figure 12.9 Najafi et al. (2017) has demonstrated that by daily use of plantar electrical stimulation
at the heel and forefoot area using a wearable plantar electrical stimulation device, some of the risk
factors associated with diabetic foot ulcers could be reduced. More specifically, six weeks daily use
of plantar sensation led to significant improvement in plantar sensation, gait, and balance whilst
reducing pain and increasing skin perfusion in the sub-sample who had high ankle brachial index
(ABI > 1.20). https://pubmed.ncbi.nlm.nih.gov/28627217-using-plantar-electrical-stimulation-to-
improve-postural-balance-and-plantar-sensation-among-patients-with-diabetic-peripheral-
neuropathy-a-randomized-double-blinded-study/?from_term=najafi+stimulation+foot&from_pos=2.
218 12 Smart Technology for the Diabetic Foot in Remission

the control group were gait, balance, and overall pain. In their study, they used an off the
shelf wearable technology (SENSUS, Neurometrix Inc., Waltham, MA, USA), which is
transcutaneous electrical nerve stimulator (TENS) system. However, they modified the sys-
tem to provide electrical stimulation (~30 milliamps) to plantar area via two electrodes
placed on hind and forefoot area instead of leg. Considering the lack of plantar sensation
in people with DPN, this configuration seems to be more acceptable and less inconvenient
as suggested by near 100% compliance to daily use therapy according to their survey. The
study consisted of a six-week treatment phase of daily use of plantar electrical stimulations
and the outcomes were assessed every two weeks.
In 2012, Rawe et al. [100] has developed a lightweight battery-powered wearable device,
which provide pulsed radio frequency energy for duration of six to eight hours. They
­suggested that daily use of this device for a period of six weeks could be effective to speed
up wound healing. However, only four patients were tested using the mechanism and no
control group was used as a comparator. Later on, in 2016, Kadry et al. [101], investigated
the efficacy of pulsed radio frequency energy as physical therapy modality in the treatment
of chronic lower limb ulcers. Forty patients who had chronic unhealed lower limb ulcers
(DFU) for longer than three months participated in this study. Then, they randomly
assigned to two groups. One group (intervention) received pulsed radio frequency with
pulse width 400 ms, 70 pulses per second with average power of 23 w for 30 minutes, three
sessions per week for six weeks and medical care. The other group (control), received
­medical care only. Their results suggest that magnitude of wound area reduction in the
intervention group is significantly higher than control group.

12.9 ­Conclusion

We live in a world where technology is increasingly being integrated into every aspect of
our lives. With the miniaturization of processors, advancements in sensing technologies,
consistent availability of electrical power, ubiquity of access to the Internet, and significant
strides in machine learning and artificial intelligence, new emerging solutions have been
developed to improve health care delivery, patient satisfaction, and population health
across different disciplines whilst reducing the cost of care.
The emergence of ‘smart’ technologies and wearable electronics paves the way for the
integration of both in the context of providing patients and clinicians with objective data
about patient health that is easily accessible. Physicians no longer need to rely on the sub-
jective history given by neuropathic patients who lack the ability to sense the deterioration
of their own bodies [102].
Technologies such as IoT and wearables enable cutting down on in-person visits and
allow physicians to remotely check in on patients, track patient adherence to the therapy,
and detect the early stages of serious medical conditions (e.g. sign of plantar inflammation
before breakdown of skin) and triage those who need an immediate supervised care.
Technology can be used to supplement healthcare provider diabetic foot care by providing
both educational and motivational support (e.g. gamification and real-time notification
systems). The advances in sensing technologies enables the collection of valuable objective
data from plantar pressure, plantar temperature, sustained plantar loading (e.g. unbroken
 ­Reference 219

prolonged standing), dosage of weight bearing activities (e.g. standing and walking), and
many more indicators to provide timely intervention to prevent DFUs, whilst promoting
safe mobility. Whilst, the application of such technology for effectiveness of diabetic foot
care is still in infancy and its cost effectiveness is still debated, by exponential speed of
technology development and exponential increase in technology investment for health
care application, it is anticipated that healthcare and care delivery for chronic conditions
such as diabetic foot will be dramatically changed in a near future.

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 225

13

How to Assess the Quality of Clinical Trials for Diabetic

Foot Ulcer Therapies
Fran Game1 and William Jeffcoate2
1
Department of Diabetes and Endocrinology, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK
2
Nottingham University Hospitals NHS Trust, Nottingham, UK

13.1 ­Introduction

It is well established that across the world the number of people developing diabetes is now
becoming a global health crisis. It is also well recognized that the number of people suffering
as a consequence of complications of diabetes is equally threatening. In particular the per-
sonal and financial consequences of people developing foot disease as a result of diabetes is
increasingly recognized. Data from both the USA and the UK have recently described the
financial scale of the problem. It is estimated in the USA that the management of diabetic
foot disease may add an additional $9–$13 billion annual cost above the costs associated with
diabetes itself [1]. A recent publication from the UK similarly highlighted the enormous
financial burden to the NHS estimating spending of £972 m. – £1.13bn. on healthcare related
to foot ulceration and amputation in diabetes in 2014–2015; equivalent to 0.72–0.83% of the
entire NHS budget [2] and approximately 10% of the total diabetes budget [3]. However,
despite these high clinical costs it appears that published research on diabetic foot ulcers and
their management is disproportionately low (Figure 13.1); in 2016 only 1.3% of the total peer
reviewed diabetes publications [4] was related to the diabetic foot.
However, it is not just the number of the publications in this field that is of concern, but
also the quality. Successive systematic reviews of the International Working Group of the
Diabetic Foot (IWGDF) have highlighted the limited number of quality papers published
[5–8], and that therefore the evidence to support many management decisions is scarce.
Given that there is no shortage of guidance available on the general principles of trial
design, this lack of good evidence is puzzling. However, these guidelines are generic in
nature and are not sufficiently specific to the complex clinical area of foot ulcers in diabe-
tes. Generic guidelines include the CONSORT statement for randomized trials [9], STROBE
for epidemiological studies [10], and PRISMA for systemic reviews and meta‐analyses [11].
There also already exist systems for scoring studies of different design [12] and guidance on
the evaluation of published evidence – notably the GRADE system [13]. The application of
these principles for studies of chronic wounds has been embraced in two guidance

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
226 13 How to Assess the Quality of Clinical Trials for Diabetic Foot Ulcer Therapies

Publications
40000

DFUs
35000 600
500

30000 400
300
200
25000
100
0
20000 1985 1990 1995 2000 2005 2010 2015 2020

15000

10000

DFU Diabetes

5000

0
87
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
03
04
05
06
07
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09
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12
13
14
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20
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19
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19
19
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19
20

20
20
20
20
20
20
20
20

Figure 13.1 Data extracted from PubMed up to 2016 showing the disporportionately low
numbers of publications related to diabetic foot ulcers compared to all of diabetes.

­ ocuments published by the European Wound Management Association (EWMA) [14, 15]
d
but none have been produced to date that are specific for studies in this field. Part of the
reason for this lies in the large number of variously overlapping processes involved in the
development and presentation of foot ulcers – as well as in their protracted healing – and
the effect these have on all aspects of trial design.
It is for these reasons that members of the IWGDF and EWMA came to together to pro-
duce guidance specifically to support researchers and readers of trials relating to wound
healing of diabetic foot wounds in establishing the quality of the trial design and conduct
[16]. Whilst that article also considered studies looking at prevention of foot ulcers in
patients with diabetes, this chapter considers only the patient who has an ulcer, and
­considers only the assessment of trials to improve wound healing.

13.2 ­Hierarchy of Evidence

There exists a hierarchy of the quality of evidence for interventions intended to improve a
clinical condition, traditionally represented as a pyramid (Figure 13.2). Case reports and
case series are seen at the bottom of the pyramid, as in themselves they provide no evidence
that the intervention applied was actually the cause of any improvement seen, although
they can provide safety information. Randomized controlled trials (RCTs) and systematic
review/meta‐analyses are usually seen at the top. Some have argued, however, that this
pyramid should not be portrayed as rigidly as this image depicts [17]. For example an RCT
 13.4 ­The Populatio 227

Systematic
reviews
meta-
analyses

Randomised
controlled trials

Cohort studies

Case control studies

Case series/reports

Figure 13.2 The traditional representation of the hierarchy of quality of evidence.

may be of such poor quality with such a high risk of bias, that the quality of evidence it
supports may be worse than a well conducted and relevant cohort study. They also suggest
that systematic reviews and meta‐analyses should be removed from the top of the pyramid
as they are not evidence themselves, are subject to the same influences of poor quality and
bias in their design and conduct, and should therefore be considered a lens through which
the evidence can be viewed rather than evidence in themselves [17].
The following discusses the evaluation of studies other than case reports and series.

13.3 ­Items to Be Considered in Assessing Trials of Diabetic

Foot Ulcer Therapies

It is important that when a trial of a specific therapy is being considered, that other inter-
ventions already well established as influencing the outcome of the diabetic foot ulcers are
identified, described and, as far as possible, matched between all groups involved in a study.
These can be divided into population factors, person and limb factors, and ulcer factors.

13.4 ­The Population

The first question to be asked is that of the relevance of the population to which the inter-
vention is being applied. Is the population generally that seen in a diabetic foot clinic? Are
the patients of an age and gender that is usually seen in a diabetic foot clinic? For example,
it would be unusual for a study to have a majority of female patients under the age of 50
and this should raise suspicions about bias in patient selection. Is it a population for which
228 13 How to Assess the Quality of Clinical Trials for Diabetic Foot Ulcer Therapies

a new treatment would be of benefit (e.g. ‘hard to heal’ ulcers), and is the population
­sufficiently well‐described to make this judgement? If, for example, the population is a
mixed one of leg ulcers and foot ulcers, the pathogenesis of which is quite different, then is
sufficient information given to be able to evaluate the populations separately? The setting
of the population is also important: what sort of environment was required for the inter-
vention, a specialist hospital setting, a community setting or the patient’s own home? The
generalisability of an intervention and standard of usual care (see later) will depend on
these details and need to be available.

13.5 ­The Person and Limb

There are a number of clinical and pathological entities which are known to affect healing
of diabetic foot ulcers, and which must be therefore well described in any study of diabetic
foot ulcers.
Features of the person that have been shown to be associated with the outcome of dia-
betic foot disease include: age, duration of diabetes, immobility, other complications of
diabetes such as heart failure, visual failure [18, 19] and renal disease, particularly con-
comitant renal replacement therapy [20].
Looking at the features of the limb which will affect outcome of foot ulcers in diabetes,
then that with the strongest influence by far is the presence of peripheral arterial disease
(PAD), although this may be less apparent in areas of the world where arterial disease is
less prevalent [21]. Its definition in trials of interventions of diabetic foot ulcer therapies
therefore needs careful consideration. Whether or not peripheral pulses are palpable
should be considered a minimal requirement, however more detail may be needed in many
circumstances. In particular, a more detailed assessment will be expected if the trial is pri-
marily of an intervention to improve peripheral perfusion and thereby wound healing,
rather than an intervention aimed directly at the wound. If the latter, then it would still be
important for there to be greater detail than simple pulse palpation to define the presence
of PAD, as this is known to be poorly reproducible in clinical practice [22]. Although it is
well recognized that bedside measures of PAD such as transcutaneous pressure of oxygen
(TcPO2) and ankle brachial pressure index (ABPI) are affected by the presence of neuropa-
thy in diabetes either directly or indirectly through arterial calcification, and therefore their
utility in clinical practice may be less than ideal, they are an important adjunct in defining
a population beyond pulse palpation. However, if the study is looking at an intervention for
improving perfusion then much more detail would be expected including measures such as
TcPO2, ABPI, and toe brachial pressure index (TBI), smoking history, previous vascular
surgery, the presence of symptoms of PAD, details of the anatomy of the arterial disease,
and the mobility of the patient [16].
A description of the presence of peripheral sensory neuropathy will also be expected at
baseline in intervention studies, not least because its presence would necessitate appropri-
ate offloading as a standard of usual care should the ulcers be on the plantar surface of the
foot. It is not sufficient, however, for there to be a simple statement of the presence or
absence of this complication of diabetes, but the tests used to define it, and how they are
 13.6 ­The Ulce 229

interpreted need to be stated, to ensure reproducibility of the study in the future. As a bare
minimum neuropathy should be defined by the presence or absence of sensation of, for
example, a 10 g monofilament, but also the sites at which this was tested and at how many
of these the patient failed to feel the monofilament need to be stated.

13.6 ­The Ulcer
The ulcer needs to be described, particularly those features which are associated with
delayed healing, e.g. size (area), depth, duration, site on the foot [18, 19, 21]. Many classifi-
cation systems exist for definition of a diabetic foot ulcer [23] but few have the level of
detail required to fully describe the important features of ulcers in a trial population. If
there are multiple ulcers (which in itself should be described as it conveys an adverse prog-
nosis) then one, usually the largest or most clinically significant, should be chosen as the
‘index ulcer’ if the outcome is ulcer healing. If, however the outcome of choice is being
ulcer free then all must be considered.

13.6.1 Area and Depth

Both are important as prognostic features, and both should be described, as should the
methods of measurement. Whether the area was measured pre‐or post debridement
should be stated. Depth can be defined by absolute measurement (e.g. in mm), but is more
frequently defined anatomically (e.g. superficial, down to tendon or joint capsule, or down
to bone) as this is the feature that is associated with healing outcome of diabetic foot
ulcers [21, 24].

13.6.2 Site
Site is important as it is known that heel ulcers take longer to heal than forefoot ulcers [19, 25],
and should therefore always be defined.

13.6.3 Infection
The presence of clinical infection is also an adverse prognostic factor. If present, it needs
to be stated, as do the definitions used for its diagnosis. Studies of infection fall into two
broad types: those in which prevention or eradication of infection is the primary outcome
measure and those in which infection is treated as part of overall care – in which case,
healing might be the primary outcome, and the level of detail required for each will be
different. If the first, then additional details required would include the history of antimi-
crobial use including route, detail of the severity of infection (for example using the
Infectious Diseases Society of America (IDSA) Criteria [26]), depth of infection and how
defined (e.g. the diagnosis of osteomyelitis) microbiological sampling, how they were
taken, and results [16].
230 13 How to Assess the Quality of Clinical Trials for Diabetic Foot Ulcer Therapies

13.7 ­The Therapy

The therapy or intervention which is the subject of the clinical trial needs to be described
in sufficient detail, such that others can reproduce the trial should confirmation be
required, and also so that it can be reproduced and rapidly adopted into clinical practice
should the trial be successful.
However, what would be important for a new therapy or intervention to be introduced
into clinical practice post trial would be that the therapy was shown to be beneficial above
and beyond what should be considered current best practice according to national and
international guidance [27, 28]. Thus, it is important that the management of the com-
parator group is defined and should be according to current best practice. The only differ-
ence between the intervention and comparator groups should be the application of the
investigational therapy or intervention.
The principles of good standard of usual care which should be defined include:
●● Formal assessment of the ulcer and surrounding skin at each clinic review
●● Provision of any necessary off‐loading, with detailed description of the type
●● Debridement of the wound surface which may be surgical/’sharp’ or non‐surgical
●● Selection of appropriate dressing products
●● Appropriate antibiotic therapy (for clinically infected wounds)
●● Optimal glycaemic control
●● Assessment for PAD, with consideration of revascularisation where appropriate
●● Continued close observation with appropriate adjustment of management

13.8 ­Outcomes

As with the baseline characteristics, outcomes need to be carefully defined and can be
grouped into person, limb, and ulcer‐related.

13.8.1 ­Person Outcomes
Depending on the length of the study then, unfortunately, there may be significant ­mortality
[29] of patients included in trials of patients with ulcers of the foot in diabetes, and this
needs to be documented. Quality of life may also be an important outcome, but the tools
used to capture this, and that they are directed towards the outcome of interest need to be
appropriate for patients with this disorder.
Increasing interest has been recently directed towards person centred outcomes which
encompass mortality, limb salvage, and ulcer healing, and which are of direct importance
to the patient [30]. One longitudinal single centre study [31] noted that although 66% of
patients’ ulcers had healed within a 12 month period only 49% of patients were alive,
amputation and ulcer free in the same period. This is of clear importance, not just to
patients, but to health care providers and funders.
 13.10 ­21 Point Checklis 231

13.8.2 ­Limb Outcomes
Obviously if a patient loses part or the whole of the index limb surgically then that surgical
procedure needs to have been captured. It is not enough just to count ‘lower extremity
amputations’.
Such surgery should be defined as:
●● surgical debridement with/without local intervention such as grafting
●● minor amputation (which is usually defined as transverse removal of part of the lower
limb below the ankle joint)
●● major amputation (transtibial, through knee, transfemoral) [32].

13.8.3 ­Ulcer-Related Outcomes
13.8.3.1 Healing
Ulcer healing is the usual primary outcome for most trials of therapies or interventions,
however it is poorly defined in many [5]. It is usually defined as complete epithelialisation
after removal of callus, without discharge, and which is maintained for a minimum of two
weeks [33]. However, it is also important to know if healing occurred as a result of surgical
closure, primary or skin grafting, or whether by secondary intention.
The time at which healing is assessed also needs careful definition, whether this be at a
fixed time point (which ought to be appropriate for the type of ulcer being followed) or the
time to healing of those that have healed. Change in ulcer area is often used as a surrogate
marker for eventual healing but the measurement of ulcer area, and hence any change in
area, may be problematic, as the contour of the foot underlying an ulcer is nearly always
curved which means that measurements taken from 2D digital images will not be precise.
The methods used to measure cross‐sectional area, and volume if this is an outcome there-
fore need to have been documented.

13.9 ­Adverse Events

All intervention studies, should report adverse events, particularly serious adverse events.
There may be adverse events of particular interest which may also be recorded as secondary
outcome in addition and are related to the type of therapy/intervention, for example falls or
new ulceration with a new offloading device, or new infection with an antimicrobial.

13.10 ­21 Point Checklist

In order to make decision making about the quality of trials of therapies or interventions
of the diabetic foot more transparent, a 21 point checklist (Table 13.1) has been devised by
representatives of the IWGDF and EWMA [16]. In publishing this list the authors
232 13 How to Assess the Quality of Clinical Trials for Diabetic Foot Ulcer Therapies

Table 13.1 Source: 21-point check list-reproduced with permission The Lancet, Endocrinology
and Diabetes.

Panel: 21‐point scoring system for reports of clinical studies of the prevention and
management of disease of the foot in diabetes
The desired answer for each question is intended to be ‘yes’, and each scores one point.

Study design
1) A re appropriate definitions included for the terms ‘ulcer’, ‘healing’, and all other required
aspects of the population and the outcomes?
2) Was the choice of study population appropriate for the chosen intervention and the stated
conclusions?
3) Was there a control population that was managed at the same time as those in the intervention
group or groups?
4) Is the intervention sufficiently well described to enable another researcher to replicate the study?
5) Are the components of other aspects of care described for the intervention and comparator
groups?
6) Were the participants randomised into intervention and comparator groups?
7) Were the participants randomised by an independent person or agency?
8) Was the number of participants studied in the trial based on an appropriate sample size
calculation?
9) Was the chosen primary outcome of direct clinical relevance?
10) Was the person who assessed the primary outcome or outcomes blinded to group allocation?
11) Were either the clinical researcher who cared for the wound at research visits or the
participants blinded to group allocation?

Study conduct
12) Did the study complete recruitment?
13) Was it possible to document the primary outcome in 75% or more of those recruited?
14) Were the results analysed primarily by intention‐to‐treat analysis?
15) Were appropriate statistical methods used throughout?

Outcomes
16) W as the performance in the control group of the order that would be expected in routine
clinical practice?
17) Are the results from all participating centres comparable? Answer ‘yes’ if the study was done
in only one centre.

Study reporting
18) I s the report free from errors of reporting – e.g. discrepancies between data reported in
different parts of the report?
19) Are the important strengths and weaknesses of the study discussed in a balanced way?
20) Are the conclusions supported by the findings?
21) Is the report free from any suggestion that the analysis or the conclusions could have been
substantially influenced by people with commercial or other personal interests in the
findings?
   ­Reference 233

acknowledge that it is intended as a template and, as above, one that needs further details
for certain studies, e.g. infection and PAD.
However, it is hoped that in publishing this list it will enable readers, researchers, and
policy makers in the future to make valued judgments about the quality of the evidence
they are being asked to assess.

­References
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18 Gershater, M.A., Löndahl, M., Nyberg, P. et al. (2009). Complexity of factors related to
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classification system. The contribution of depth, infection, and ischemia to risk of
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 235

14a

Bypass in Diabetic Peripheral Artery Disease

Neal R. Barshes and Joseph L. Mills
Division of Vascular Surgery and Endovascular Therapy, Michael E. DeBakey Department of Surgery, Houston, TX, USA

For nearly 50 of the first 60 years since its inception, infrainguinal bypass was the only
viable revascularization option for patients with extensive infrainguinal peripheral artery
disease (PAD). It still remains the most effective and durable means of leg revascularization
[1–3]. This chapter will describe the identification of patients who may benefit from bypass
surgery, some important aspects of these operations, and post-operative care of leg bypass
patients.

14a.1 ­Identifying Significant PAD Amongst Patients

Presenting with Foot Ulcers

The Society for Vascular Surgery, the European Society of Cardiology and the European
Society for Vascular Surgery have endorsed the Lower Extremity Threatened Limb
Classification System – also known by the acronym of ‘WIfI’ (for the components of
Wound, Ischemia, and foot Infection) as a tool to estimate risk of limb loss and benefit of
revascularization in patients with chronic limb-threatening ischemia (CLTI) [4]
(Table 14a.1). One of the most important aspects of this classification tool is its utility in
identifying PAD in patients presenting with foot ulcers, and aspects of the ‘ischemia’ com-
ponent of this tool are worth mentioning here. First, toe pressures, skin perfusion pressures
or transcutaneous oximetry are the preferred non-invasive modalities because of a higher
sensitivity in detecting PAD compared to pulse palpation, ankle pressures or ankle-brachial
indices. Second, the surgeon should strongly consider revascularization for the majority of
functional patients with non-healing wounds who have toe pressures, skin perfusion pres-
sures, or transcutaneous oximetry measurements of <30 mmHg. Revascularization should
also be considered for those with measurements ranging from 30 to 60 mmHg, with the
extent of the wound, the degree of infection, patient comorbidities, and patient preferences
being amongst the many factors that are incorporated in the shared decision-making
­process that occurs between the surgeon and the patient.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
236 14a Bypass in Diabetic Peripheral Artery Disease

Table 14a.1 Wound, Ischemia, and foot Infection grading in the Society for Vascular Surgery
Threatened Limb Classification System (also known as the WifI score) [4].

WOUND
W 0: No open lesions at this time (patient must have rest pain to have CLTI with no wound)
W 1: Small, shallow ulcer without exposed metatarsal/midfoot bone; no gangrene
W 2: Deeper ulcer with exposed bone, joint, or tendon; gangrene limited to digits
W 3: Extensive deep ulcer or gangrene of forefoot or midfoot, or deep heel ulcer with calcaneal
involvement

ISCHEMIA (note: toe pressures are preferred for perfusion assessment in patients with diabetes)
I 0: Adequate arterial perfusion ( 100 mmHg ankle or 60 mmHg at toe)
I 1: Moderately impaired arterial perfusion (ankle 70–99 or toe 40–59)
I 2: Severely impaired arterial perfusion (ankle 50–69 or 30–39 toe)
I 3: Extremely impaired arterial circulation (ankle <50 or < 30 toe)
I U: (Unknown) Cannot assess adequately at this time.

FOOT INFECTION
fI 0: No symptoms or signs of infection at this time
fI 1: Infection present involving skin +/− subcutaneous tissue only with 2+ of:
___ local swelling or induration
___ erythema >0.5 cm to 2 cm around ulcer
___ local tenderness or pain
___ local warmth
___ purulent discharge
fI 2: Erythema >2 cm or deep infection, incl. Abscess, osteomyelitis, septic arthritis, fasciitis
fI 3: Any of the above (fI1–3) with signs of SIRS response:
___ temperature > 38 °C or < 36 °C
___ pulse rate > 90/min
___ respiratory rate > 20/min
___ PaCO2 < 32 mmHg
___ WBC >12 K or < 4 K/microL
___ or > 10% bands

Our group has used formal decision analyses to evaluate strategies used to identify sig-
nificant PAD in patients [5]. These analyses have identified two strategies as being best to
identify PAD. The two best strategies share a common characteristic: assuming PAD is pre-
sent until excluded by at least one test. In the best (highest sensitivity) strategy, the clini-
cian first palpates for pedal pulses. In general, angiography should be performed if pulses
are weak, absent, or otherwise not readily palpable. If at least one pedal pulse is palpable,
this physical exam finding is corroborated with non-invasive testing (toe pressures, skin per-
fusion pressures or transcutaneous oximetry) to confidently rule out PAD. Solely relying on
 14a.2 ­Relative Benefits and Risks: Identifying Patients Who May Benefit from a Leg Bypass Operatio 237

palpation of pedal pulses is prone to error; this additional step of corroborating findings
with non-invasive testing increases the overall sensitivity of this approach to 92%.
The second best strategy is testing all foot ulcer patients with toe pressures, skin perfusion
pressures or transcutaneous oximetry. This approach, a component of WIfI, has an esti-
mated sensitivity of 83% but offers other advantages. Because all patients uniformly get
testing, no decision making on the ordering of non-invasive testing is needed in the field, an
advantage in health care systems with a wide variety of providers (including trainees) seeing
foot ulcer patients. Also, baseline quantitative measures are obtained in all patients, and the
number of angiograms without significant PAD findings is reduced [5].
Revascularization is generally not indicated if toe pressures, skin perfusion pressures, or
transcutaneous oximetry levels are above 60 mmHg. That said, angiography should be con-
sidered for patients with wounds that are not healing despite having had infection and
offloading addressed. This recommendation is based on the fact that whilst toe pressures,
skin perfusion pressures, and transcutaneous oximetry testing have negative predictive val-
ues in the range of 86–93% [5], about one in 10 patients with significant PAD will therefore
not be identified by these tests.

14a.2 ­Relative Benefits and Risks: Identifying Patients

Who May Benefit from a Leg Bypass Operation

There are several reasons to justify a liberal approach to offering leg bypass operations.
First, as mentioned initially, these operations are effective, as 85–90% of patients who have
undergone an infrainguinal bypass for a foot ulcer or for gangrene should still have their
foot one year after the operation. These operations are also durable, with five-year second-
ary patency rates of 60–70% and five-year limb preservation rates of 70–80%. Although the
long-term survival of foot ulcer patients is often reported as approximately 50% at 5 years,
this is mainly due to comorbidities: the 30-day perioperative mortality associated with
infrainguinal bypass in foot ulcer patients is only 2.6% (see review [6]). Finally, surgical
bypass seems to be a cost-effective treatment option for patients with significant PAD and
non-healing foot ulcers. Specifically, when compared to wound care alone, an initial bypass
with subsequent endovascular ­revisions has an incremental cost-effectiveness ratio of
approximately 50 000 U.S. dollars per quality-adjusted life-year [7].
The term ‘critical limb ischemia (CLI)’ has lately been inappropriately applied to patients
with diabetes – a group that was specifically excluded from the original definition. The
Society for Vascular Surgery and other societies across the globe have recently advised tran-
sitioning to using the term CLTI to include a broader, more representative, real world group
of patients who have threatened limbs but do not meet the classic haemodynamic definition
of CLI. Whereas CLI implied a poor outcome in the absence of revascularization, a signifi-
cant proportion of patients in the CLTI spectrum can achieve limb salvage with close follow-
up and proper wound care even when revascularization is either not possible or
contraindicated due to frailty. For example, Marston and colleagues reported a series of 142
patients with wounds and severe limb ischemia (ankle-brachial index [ABI] <0.7 or TP
<50 mmHg) who were treated at a comprehensive wound care centre with meticulous
wound care but without revascularization [8]. The amputation rates were 19% at 6 months
238 14a Bypass in Diabetic Peripheral Artery Disease

and 23% at 12 months. Wound healing with conservative management was reported in 52%
of patients at 12 months [6]. Another study by Elgzyri and colleagues evaluated 602 patients
with diabetic foot ulcers who had either a systolic TP < 45 mmHg or an AP < 80 mmHg who
were not revascularized and reported that 50% healed primarily with wound care or only minor
amputation; 17% healed after requiring a major amputation; and 33% died with their affected
limbs intact but with unhealed wounds. The authors concluded that ‘diabetic patients with
ischemic foot ulcers not available for revascularization are not excluded from healing with-
out major amputation. Our findings reinforce the need for a classification system consider-
ing these factors at decision’ [9]. These observations highlight the challenges in interpreting
limb salvage and amputation-free survival outcomes in the literature, especially when mak-
ing comparisons between different reports or non-randomized groups. Such observations
have been factored into the development of the SVS WifI threatened limb classification.
In addition, recent data suggest that WIfI may also assist in predicting which patients
might fare better with bypass as opposed to endovascular therapy. Kobayashi and col-
leagues reported that when endovascular therapy alone was applied to Clinical Stage 4
WIfI patients, results were worse than in lower stage patients. Specifically, the wound heal-
ing rate was only 44%, the major limb amputation rate was 20 and 46% of patients required
multiple endovascular procedures by one year. In a non-randomized comparison in WIfI
Clinical Stage 4 patients, Ramanan et al. found that freedom from major limb amputation
was superior in patients who underwent bypass compared to those who underwent endo-
vascular therapy [9]. If these results can be confirmed, WIfI may prove to be a useful limb
staging tool to select endovascular therapy or open bypass in patients with CLTI.
It also is worth discussing groups of patients who may not benefit from revascularization.
The most obvious of these groups would be patients who have absolutely no function in the
affected limb and are completely non-ambulatory. Neurologic conditions, especially com-
plete spinal cord injury or debilitating stroke with severe residual deficit, are amongst the
most common reasons why someone may have no limb function. In these patients, the
degree of disability is obvious, and through-knee amputation or minor amputation with
palliative wound care may be the better options for many in this group [10].
In patients who present with severe frailty or deconditioning, assessment is more chal-
lenging because the degree of disability is relative. In this group, patients may have been
bedridden whilst recovering from a severe pneumonia, coronary event, or other medical
illness, resulting in a decrease in function from baseline lasting more than two weeks.
Muscular contractures that limit full joint extension may be present. The surgeon should
discuss revascularization based on the rehabilitation potential of patients in this group
rather than based on current functional status or any particular number measured with a
goniometer. Herein, though, lies a challenge, as individual-level predictions have very lim-
ited accuracy. The authors would therefore suggest a liberal offer of revascularization here
too. As discussed above, it is important to distinguish between the patients with no limb
function and those who have low baseline function but do use the affected limb for trans-
fers, short distance walking, or other important daily activities, as these latter patients
would often benefit from revascularization.
Indeed, formal cost-utility analyses done with probabilistic Markov models suggest that
revascularization of frail, marginal patients may have more potential for cost-savings (that is,
better outcomes and lower cost than other treatment strategies) than revascularization of
 14a.3 ­Evaluating Relevant Vascular Anatomy for Planning a Bypass Operatio 239

patients with higher baseline function [11]. This may seem counterintuitive, but it is based
on the fact that the difference in functional outcomes between limb salvage and leg amputa-
tion strategies is greater in more marginal patients. In other words, patients who are rela-
tively younger and more active at baseline do well with limb salvage efforts, but would also
have reasonable functional outcomes with leg amputation. In contrast, elderly frail patients
who have very marginal baseline function are barely functioning with their own limb.
Whereas limb preservation can effectively maintain this marginal functional status, previous
reports have suggested that these patients are at a much higher risk of suffering significant
decreases in functional status when leg amputation is performed. So although the outcomes
of limb salvage in these patients may be poorer than that of younger patients when meas-
ured in absolute terms, the relative benefit may actually be greater when compared to the
outcomes of leg amputation within the same patient cohort [11]. See Figure 14a.2.
As with all management decisions, the surgeon should weigh the patient’s preferences in
the revascularization decision-making. That said, the surgeon should refrain from enticing
the patient with the promise that a leg amputation operation would be a safer choice or the
‘one-and-done’ choice for a faster recovery. When compared to infrainguinal bypass in a risk-
adjusted propensity analysis, patients with significant comorbidities have a higher 30-day
perioperative mortality with leg amputation [12]. It is estimated that about 20–25% of those
undergoing major (above-ankle) amputation will return to the operating room for wound
healing complications, and 16% of leg amputation incisions will remain unhealed at one year
(see review [6]). Whereas foot debridement or minor (toe or partial foot) amputations can
almost uniformly be done with ankle block anaesthesia, revision of a leg amputation will
more often require epidural, spinal, or general anaesthesia. Finally, the surgeon must give
patients a realistic expectation of function following leg amputation: amongst ambulatory
patients living in the community, only about half will remain ambulatory with a prosthesis
following leg amputation, and about 20% will require support in a nursing home [6].
In summary, weighing the relative benefits and risks of revascularization is more calcu-
lus than arithmetic. All of the aforementioned factors and others should all be incorpo-
rated into a qualitative process that should be biased towards revascularisation in the large
proportion of patients in whom this is anatomically possible. Palliative wound care – with
minor amputations, drainage, or debridement as needed – should be offered to most other
patients who are not considered candidates for revascularization. Leg amputation should
most often be reserved for the uncommon situation of a patient who is not a candidate for
revascularization and whose function may actually improve following this operation,
though it may be reasonable to consider this option for patients with ongoing or recurrent
infection, large open wounds, or extensive areas of gangrene.

14a.3 ­Evaluating Relevant Vascular Anatomy for Planning

a Bypass Operation

The surgeon does need to ensure some basic anatomic requirements prior to a leg bypass
operation. The first requirement is the presence of a suitable ‘target’ vessel: a patent seg-
ment of artery distal to the occluded segments that is expected to adequately reperfuse the
foot. It is preferable that this artery be in continuity with either the dorsalis pedis artery and
240 14a Bypass in Diabetic Peripheral Artery Disease

Figure 14a.1 Digital subtraction

angiography showing reconstitution of the
dorsalis pedis artery in a patient with
occlusion of all three named tibial vessels.
This vessel would be an adequate distal
target for revascularization.

its branches or the lateral plantar artery and its branches. This is not an absolute require-
ment, as surgeons have reported acceptable limb salvage results with bypasses to both iso-
lated tibial segments [13] (that is, segments that are not in direct continuity with pedal
vessels) and to pedal artery branches [14, 15]. Good quality angiograms performed with
digital subtraction (Figure 14a.1) or magnetic resonance imaging are the best imaging
modalities to identify an adequate distal target. These studies should include AP (antero-
posterior) and lateral views of the foot itself. With good imaging and an aggressive approach
to identifying an acceptable target, no more than one in 10 patients evaluated should be
excluded from a leg bypass operation solely on the basis of poor distal targets.
The patient should also be examined for the presence of an adequate autologous venous
conduit, either by the surgeon or by an experienced sonographer. A vein that is at least
3.5 mm in diameter and compressible throughout its length is generally considered ade-
quate. Examination should start with the ipsilateral great saphenous vein, then go to the
contralateral great saphenous vein, then arm veins (upper arm and forearm cephalic and
basilic veins), then the small saphenous veins in the posterior calf. The length of available
vein can be measured using a tape measure, a silk tie, or an umbilical tape. As a rule of
thumb, the length of a person’s lower extremity is just under half his height. The femur and
the tibia are about equal in length. The required length of arm veins for common femoral
 14a.4 ­The Operation and Early In-Hospital Recover 241

consider limb preservation efforts

100%
Probability of post-operative ambulation

consider consider minor

consider major
major amputation &

on
amputation vs.
amputation

a ti
palliative limb preservation

ion
80%

er v
wound care

ta t
res

pu
bp

am
lim

jor
60%

ith

ma
gw

r
fte
tin
Benefit derived from

ga
la
limb preservation

bu

tin
40%

am

la
bu
of

am
ity

of
bil

20%
ba

ity
Pro

bil
ba
Pro
0%
Baseline (pre-operative) function

Figure 14a.2 The relative benefit of limb preservation as a function of baseline functional status.

to dorsalis pedis artery bypass in a 5 ft, 10 in. (178 cm) man would therefore be at least 35 in.
(89 cm), whilst a bypass from the popliteal artery to the dorsalis pedis artery would require
at least 18 in. (46 cm).
Finally, the patient should be evaluated by anesthesiologists and/or physicians prior to
elective operations as per local protocols. Infrainguinal operations are not associated with
large fluid shifts or fluid losses, aortic cross-clamping, or other significant physiologic per-
turbations. An evaluation for coronary artery disease need not therefore be considered
mandatory.

14a.4 ­The Operation and Early In-Hospital Recovery

Leg bypass operations are typically performed under general or spinal anaesthesia. Their
duration ranges from two to six hours, depending on bypass conduit (prosthetic vs. ipsilat-
eral vein vs. bilateral arm vein harvesting or small saphenous vein harvesting in the poste-
rior calf), scar from previous arterial operations, and the need for femoral endarterectomy
or any concomitant endovascular or surgical procedures to address aortoiliac disease.
The operation should typically start with the first steps of vein harvesting if the ipsilateral
great saphenous is the chosen conduit. When paired with ultrasound mapping and mark-
ing of the vein in the pre-operative holding area, starting with vein harvesting has the
advantage of centering the incision precisely over the vein. This approach minimizes tissue
trauma, the number of tracts created to identify the vein, and avoids the creation of exces-
sively thin soft tissue flaps that could compromise incisional healing. Additionally, the vein
is protected when the same incisions are used for arterial exposure, avoiding inadvertent
thermal injury from electrocautery or sharp injury from scissors. Vein harvesting can be
initiated concomitantly with arterial exposure when upper extremity or contralateral great
saphenous vein is used and multiple surgeons are available. Once exposed, side branches
should be ligated, circumferentially isolating the vein. It should be left in situ until ready for
use, unless it is planned to be used in the reversed or non-reversed configuration and placed
242 14a Bypass in Diabetic Peripheral Artery Disease

in an anatomic tunnel. In the event that one or both small (lesser) saphenous veins are to
be used, two options exist: either the vein is harvested in supine position with an assistant
lifting the leg; or it is harvested and excised with the patient prone, then the patient is repo-
sitioned to complete the bypass operation. Both authors (NRB and JLM) favour the latter
approach to minimize trauma to the vein and allow careful reapproximation of the incision.
Fewer vascular than cardiac surgeons utilize endoscopic vein harvesting, probably because
of the impaired graft patency that has been shown in many studies [16].
There is no established advantage of using the vein in a reversed versus a non-reversed
direction. A reversed vein graft avoids the use of a valvulotome, which could potentially
induce intimal damage. A non-reversed vein graft, on the other hand, fully utilizes the
proximal (larger-calibre) end of the graft and better matches the calibre of the involved
arteries (i.e. large calibre end connected to the larger inflow artery, small calibre end
­connected to the smaller-calibre distal target artery).
For situations in which adequate autogenous vein is truly not available for an infrap-
opliteal bypass, polytetrafluoroethylene (PTFE) prosthetic conduit is preferred. It can also
be a suitable and cost-effective alternative to spliced vein when great saphenous vein is not
available [17, 18]. A distal vein patch or a pre-cuffed PTFE graft should generally be used
when prosthetic conduit is used for tibial targets. The use of cryopreserved allografts should
be reserved for very select circumstances, as the long-term patency of these grafts is poor
[19]. Some such circumstances may include a pedal target in patients without adequate
autogenous conduit or ongoing infection or gangrene at or near a proposed incision.
The approach to graft tunnelling should consider several factors. Anatomic tunnelling is
typically the shortest distance between the inflow and outflow sites; this therefore affords
an advantage for a slightly shorter vein graft. This is especially true for grafts originating
from the mid- or distal superficial femoral artery or from the popliteal artery. Subcutaneous
tunnelling allows for easier monitoring, both via palpation by the surgeon and the patient
and via ultrasound surveillance by the sonographer. Because nearly 50% of spliced vein
conduits merit re-intervention (endovascular or open) during follow-up [20], subcutane-
ous tunnelling should be favoured for most spliced vein conduits. Except for bypasses to
the anterior tibial artery, PTFE grafts should generally be tunnelled in an anatomic fashion
since the aforementioned benefits of subcutaneous tunnelling of vein grafts are not rele-
vant to ­prosthetic conduits.
Wound healing complications do occur in up to 30% of leg incisions, even in contempo-
rary reports [21]. Early observational studies of negative pressure wound therapy dressings
for closed vascular surgical incisions appeared promising [22], but a subsequent trial has
failed to show significant benefit [23]. The authors strongly favour subcuticular suture clo-
sure of all incisions, strict avoidance of skin staples in the groin, avoidance of hospitalization
prior to surgery, and a pre-operative decontamination protocol for colonization of methicil-
lin-resistant Staphylococcus aureus based on an analysis demonstrating these factors have
significantly decreased wound complications at his centre [24].
Patients remain in the hospital for four to seven days after an uncomplicated case. Initial
monitoring over a 12–24 hours is sometimes done in the intensive care unit if significant
comorbidities are present, and the remainder of the hospital time is in a regular inpatient
unit. The hospital stay focuses on pain control, physical therapy, and continuing or initiat-
ing a management plan for the instigating foot wound and any associated infection. Many
 ­Reference 243

surgeons use a gentle elastic wrap on the leg to minimize postoperative swelling. The
patient is instructed to not bear weight on the foot with an open plantar foot wound.

14a.5 ­Follow-Up After a Leg Bypass Operation

Patients return to the clinic within one to two weeks and again at four to six weeks from
discharge from the hospital, unless they need to be seen sooner for wound care. The leg
edema that is common early after the operation should be greatly improved by the six week
visit. There should also be unequivocal improvement in the wound (generally, a 50%
decrease in the depth and/or surface area) by four weeks. Failure of the index wound to
improve should prompt repeat staging using the WIfI classification system to include an
evaluation for residual infection, adequacy of offloading and reassessment of the perfusion
(graft duplex imaging and toe pressures and waveforms).
It is important that the surgeon personally direct or work closely with others to accom-
plish the goal of achieving complete wound healing, ideally within the first year from the
time of the bypass operation. Indeed, this should be done as expeditiously as possible.
Several studies suggest that if complete one healing can be achieved-especially soon after
the operation – then the risk of recurrence infections and the risk of leg infections go down
significantly.
Leg bypass grafts in the United States often receive Duplex ultrasound surveillance, espe-
cially those done using autogenous vein. This is most often performed at 3-month intervals
for the first 12–18 months, then yearly thereafter. It may be reasonable to get an initial,
early ultrasound at sometime ranging between one and three months after bypass opera-
tion for patients who have spliced vein or other high risk conduits [25]; otherwise, the first
ultrasound should be done at three months after surgery [26, 27].

R
­ eferences

1 Donaldson, M.C., Mannick, J.A., and Whittemore, A.D. (1991). Femoral-distal bypass with
in situ greater saphenous vein. Long-term results using the Mills valvulotome. Ann. Surg.
213 (5): 457–464; discussion 464-465.
2 Albers, M., Romiti, M., De Luccia, N. et al. (2007). An updated meta-analysis of
infrainguinal arterial reconstruction in patients with end-stage renal disease. J. Vasc. Surg.
45 (3): 536–542.
3 Pomposelli, F.B., Kansal, N., Hamdan, A.D. et al. (2003). A decade of experience with
dorsalis pedis artery bypass: analysis of outcome in more than 1000 cases. J. Vasc. Surg. 37
(2): 307–315.
4 Mills, J.L. Sr., Conte, M.S., Armstrong, D.G. et al. (2014). The Society for Vascular Surgery
Lower Extremity Threatened Limb Classification System: risk stratification based on wound,
ischemia, and foot infection (WIfI). J. Vasc. Surg. 59 (1): 220–234.e1-2.
5 Barshes, N.R., Flores, E., Belkin, M. et al. (2016). The accuracy and cost-effectiveness of
strategies used to identify peripheral artery disease among patients with diabetic foot ulcers.
J. Vasc. Surg. 64 (6): 1682–1690.e3.
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6 Barshes, N.R. and Belkin, M. (2011). A framework for the evaluation of “value” and
cost-effectiveness in the management of critical limb ischemia. J. Am. Coll. Surg. 213 (4):
552–566.e5.
7 Barshes, N.R., Chambers, J.D., Cohen, J., and Belkin, M. (2012). Cost-effectiveness in the
contemporary management of critical limb ischemia with tissue loss. J. Vasc. Surg. 56 (4):
1015–1024.e1.
8 Kobayashi, N., Hirano, K., Yamawaki, M. et al. (2017). Characteristics and clinical
outcomes of repeat endovascular therapy after infrapopliteal balloon angioplasty in
patients with critical limb ischemia. Catheter. Cardiovasc. Interv.: 11.
9 Elgzyri, T., Larsson, J., Thörne, J. et al. (2013). Outcome of ischemic foot ulcer in diabetic
patients who had no invasive vascular intervention. Eur. J. Vasc. Endovasc. Surg. 46 (1):
110–117.
10 Barshes, N.R., Gold, B., Garcia, A. et al. (2014). Minor amputation and palliative wound
care as a strategy to avoid major amputation in patients with foot infections and severe
peripheral arterial disease. Int. J. Low Extrem. Wounds 13 (3): 211–219.
11 Barshes, N.R., Kougias, P., Ozaki, C.K. et al. (2014). Cost-effectiveness of revascularization
for limb preservation in patients with marginal functional status. Ann. Vasc. Surg. 28 (1):
10–17.
12 Barshes, N.R., Menard, M.T., Nguyen, L.L. et al. (2011). Infrainguinal bypass is associated
with lower perioperative mortality than major amputation in high-risk surgical candidates.
J. Vasc. Surg. 53 (5): 1251–1259.e1.
13 Brewster, D.C., Charlesworth, P.M., Monahan, J.E. et al. (1984 Jul). Isolated popliteal
segment v tibial bypass. Comparison of hemodynamic and clinical results. Arch. Surg. Chic
Ill 1960 119 (7): 775–779.
14 Saarinen, E., Kauhanen, P., Söderström, M. et al. (2016). Long-term results of
Inframalleolar bypass for critical limb Ischaemia. Eur. J. Vasc. Endovasc. Surg. 52 (6):
815–822.
15 Brochado-Neto, F.C., Cury, M.V.M., Bonadiman, S.S.T. et al. (2012). Vein bypasses to
branches of pedal arteries. J. Vasc. Surg. 55 (3): 746–752.
16 Jauhari, Y.A., Hughes, C.O., Black, S.A. et al. (2014). Endoscopic vein harvesting in lower
extremity arterial bypass: a systematic review. Eur. J. Vasc. Endovasc. Surg. 47 (6): 621–639.
17 Barshes, N.R., Ozaki, C.K., Kougias, P., and Belkin, M. (2013). A cost-effectiveness analysis
of infrainguinal bypass in the absence of great saphenous vein conduit. J. Vasc. Surg. 57 (6):
1466–1470.
18 McPhee, J.T., Barshes, N.R., Ozaki, C.K. et al. (2012). Optimal conduit choice in the
absence of single-segment great saphenous vein for below-knee popliteal bypass. J. Vasc.
Surg. 55 (4): 1008–1014.
19 Albers, M., Romiti, M., Pereira, C.A.B. et al. (2004). Meta-analysis of allograft bypass
grafting to infrapopliteal arteries. Eur. J. Vasc. Endovasc. Surg. 28 (5): 462–472.
20 Albers, M., Romiti, M., Brochado-Neto, F.C., and Pereira, C.A.B. (2005). Meta-analysis of
alternate autologous vein bypass grafts to infrapopliteal arteries. J. Vasc. Surg. 42 (3):
449–455.
21 Ozaki, C.K., Hamdan, A.D., Barshes, N.R. et al. (2015). Prospective, randomized, multi-
institutional clinical trial of a silver alginate dressing to reduce lower extremity vascular
surgery wound complications. J. Vasc. Surg. 61 (2): 419–427.e1.
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22 Matatov, T., Reddy, K.N., Doucet, L.D. et al. (2013). Experience with a new negative
pressure incision management system in prevention of groin wound infection in vascular
surgery patients. J. Vasc. Surg. 57 (3): 791–795.
23 Lee, K., Murphy, P.B., Ingves, M.V. et al. (2017). Randomized clinical trial of negative
pressure wound therapy for high-risk groin wounds in lower extremity revascularization.
J. Vasc. Surg. 66 (6): 1814–1819.
24 Zamani, N., Sharath, S.E., Vo, E. et al. (2018). A multi-component strategy to decrease
wound complications after open infra-inguinal re-vascularization. Surg. Infect. 19 (1):
87–94.
25 Ferris, B.L., Mills, J.L., Hughes, J.D. et al. (2003). Is early postoperative duplex scan
surveillance of leg bypass grafts clinically important? J. Vasc. Surg. 37 (3): 495–500.
26 Ihnat, D.M., Mills, J.L., Dawson, D.L. et al. (1999). The correlation of early flow
disturbances with the development of infrainguinal graft stenosis: a 10-year study of 341
autogenous vein grafts. J. Vasc. Surg. 30 (1): 8–15.
27 Mills, J.L., Harris, E.J., Taylor, L.M. et al. (1990). The importance of routine surveillance of
distal bypass grafts with duplex scanning: a study of 379 reversed vein grafts. J. Vasc. Surg.
12 (4): 379–386; discussion 387-389.
 247

14b

Surgery or Endovascular Intervention in Diabetic

Peripheral Vascular Disease
Edward Y. Woo and Misaki M. Kiguchi
Department of Vascular Surgery, MedStar Washington Hospital Center, Washington, DC, USA

14b.1 ­Introduction

The incidence of peripheral arterial disease (PAD) from atherosclerosis is markedly

increased in individuals with diabetes mellitus (DM). Unfortunately, atherosclerosis
and its clinical consequences cause significant morbidity and mortality in diabetic
patients, affecting all vascular beds, but in particular the lower extremity arteries [1, 2].
Although many diabetic patients are asymptomatic from their PAD, a smaller but still
significant number of patients with DM progress towards critical limb ischemia. In this
symptomatic population, the incidences of non-traumatic lower extremity amputations
and hospitalizations for chronic foot wounds are much higher than in patients without
DM [3].
Healing these wounds not only requires optimization of glycemic control, but also often
requires debridement of soft tissue infection and surgical revascularization. Open surgical
bypass has historically been the mainstay of treatment to re-establish blood flow to the
lower extremity in patients with and without DM. However, in the past decade, percutane-
ous endovascular techniques have been shown to be effective in achieving successful revas-
cularization for the purposes of wound healing. This more minimally invasive alternative
is often advantageous in a DM population already prone to infection, poor wound healing,
and cardiovascular events.

14b.2 ­Background

The true incidence of PAD within the diabetic population is difficult to measure. The con-
dition is often asymptomatic or masked by peripheral neuropathy, a common complication
of poorly controlled DM. In a population study of diabetic patients, PAD (defined as ankle-
brachial index <0.90) was identified in 20–30% of screened individuals [4]. In addition, the

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
248 14b Surgery or Endovascular Intervention in Diabetic Peripheral Vascular Disease

duration and severity of DM correlated with the increased incidence and progression of
PAD. Selvin et al. [5] report that every 1% increase in glycosylated haemoglobin (HbA1C)
increases the risk of PAD by 28%.
The pathophysiology of PAD within the diabetic population is similar in mechanism
but accelerated in severity compared to the non-diabetic population. The abnormal
­metabolic state of DM contributes to the vascular inflammation and alterations in multi-
ple cell types (e.g. endothelial cells, vascular smooth cells, platelets, etc.) that ultimately
cause deregulation of coagulation cycles and inhibit effective fibrinolysis – both of which
contribute directly to atherosclerotic development. The distribution of peripheral athero-
sclerotic disease in DM, for still unclear reasons, tends to concentrate in the tibial vessels,
often necessitating infra-popliteal revascularization [6]. Lastly, diabetic patients have a
significantly increased calcium burden found in the media of the artery wall, making
surgical management of arterial lesions more difficult in terms of risk of embolization,
treatment of primary lesions as well as re-stenosis, and decreasing the utility of non-inva-
sive vascular lab imaging.

14b.3 ­Diagnosis

Early diagnosis of PAD allows risk modification and management of existing disease
­processes. A careful history and physical exam focusing on peripheral vascular circulation
is important.
In addition, a thorough foot exam is essential. Diabetic patients have foot deformities
associated with vulnerable areas for wounds due to high pressure mechanical pressure
points. Due to inevitable peripheral neuropathy, diabetic patients often do not realise
when a wound occurs. The ankle-brachial index (ABI) is an accurate and non-invasive
method of diagnosing PAD (ABI < 0.9) in non-calcified vessels. Other, noninvasive
studies, such as pulse volume recordings and duplex ultrasonography can be very use-
ful. It is important to recognise that calcification of the arteries may cause non-com-
pressibility and result in unreliable values or readings (Figure 14b.1). Under these
conditions, toe pressures (<30 mmHg for rest pain; <50 mmHg for tissue loss) and toe-
brachial pressures (<0.70 for PAD) can be useful adjunctive diagnostic tools to diagnose
arterial insufficiency [7]. Transcutaneous oxygen tests can assess tissue perfusion if an
ankle-brachial index/toe-brachial index (ABI/TBI) cannot be performed (<40 mmHg is
associated with impaired healing) [8]. The American Diabetes Association (ADA)
­consensus statement recommends that a screening ABI be performed in diabetic indi-
viduals greater than 50 years of age and with at least one other risk factor (e.g. smoking,
hypertension, hyperlipidemia, or duration of diabetes >10 years) and in any patient
with symptoms of PAD [9].
More detailed imaging can be obtained via magnetic resonance angiography and com-
puted tomography angiography. Diagnostic angiography is the gold standard and most
accurate modality for defining PAD. Ultimately, even with acceptable non-invasive vascu-
lar lab values for wound healing, any patient with a nonhealing foot wound or rest pain,
without palpable pedal pulses should be assumed to have PAD, and thus, warrants further
work-up with a referral to vascular surgery.
 14b.3 ­Diagnosi 249

History
Smoke: Never Hypertension: Yes Diabetic: Yes
Gangrene: Left Vascular Ulcers: Both Skin Color Chg: Both
Prev Vasc Surg: Yes
Segmental BP
Right Left
Brachial: Index Brachial: 133 Index
Ankle (PT): 60 0.45 Ankle (PT): 186 1.40
Ankle (DP): 106 0.85 Ankle (DP): 166 1.25
Doppler
Right Left
Post Tibial: Monophasic Post Tibial: Triphasic
Dors. Pedis: Biphasic Dors. Pedis: Triphasic

Segmental BP
Segment/Brachial Index
R L

Brachial 133

R) Ankle L) Ankle

Gain:21% Gain:21%
60 (PT) (PT) 186
0.45 1.40
106 (DP) (DP) 166
0.80 1.25

0.80 Ankle/Brachial Index 1.40

Figure 14b.1 ABI in diabetic patient with non-compressible calcified left tibial arteries.
250 14b Surgery or Endovascular Intervention in Diabetic Peripheral Vascular Disease

14b.4 ­Management

Aggressive risk factor modification is the mainstay of medical management. Smoking

cessation, HgbA1C below 7%, low-density lipoprotein (LDL) below 100 mg/dl and blood
pressure below 130/80 mmHg are recommended treatment goals for patients with diabe-
tes and PAD. In addition, the risk of cardiovascular morbidity and mortality from PAD in
diabetic patients related to increased platelet activity can be modified by antiplatelet ther-
apy. The ADA likewise recommends that patients with DM receive antiplatelet therapy
and, moreover, those with diagnosed PAD will likely benefit more by taking clopidogrel
than aspirin [10].
Diabetic patients with PAD, especially individuals with rest pain and non-healing
wounds, often do not experience improvement in symptoms from medical therapy
alone. If a wound is infected, source control is imperative. This may involve drainage,
debridement, and at times, amputation depending on the severity of the infection.
Revascularization is critical for preventing limb loss. Any patient with a non-healing
wound and/or rest pain with abnormal non-invasive testing, including non-palpable
pedal pulses, should be considered for an angiogram. The TransAtlantic Inter-Society
Consensus (TASC) II guidelines provide a consensus statement to guide decision-mak-
ing based on disease anatomy. These guidelines, however, do not take into account tib-
ial and multilevel disease, especially in the context of patient-level factors, including
diabetes [11]. Open surgical revascularization has been the gold standard. However, in
diabetic patients who already have increased cardiovascular risk, increased wound
healing complications, and lack of vein conduit – the primary determinant of success-
ful open bypass – endovascular interventions have often become the first-line therapy
for revascularization.

14b.5 ­Endovascular Revascularization

Wound healing requires direct inline pulsatile blood flow. Proximal revascularization may
alleviate rest pain, but in diabetic patients with wounds, in whom PAD manifests often as
tibial disease, treatment of more distal arteries is also necessary for uninterrupted arterial
blood flow. Thus, in addition to treating proximal stenotic/occlusive lesions in the aorto-
iliac or femoro-popliteal arteries, the tibial arteries need to be addressed in this cohort with
PAD for optimal wound healing.

14b.5.1 Technique
After local is infiltrated into the subcutaneous skin over the femoral pulse, the Seldinger
technique is used to gain access into the common femoral artery, using a micropuncture
needle. Ultrasound should be used to guide accurate access and minimise complications.
Once the micropuncture is within the arterial lumen, the microwire is gently inserted
through the needle into the lumen of the artery. The needle is then removed over the wire
and a microsheath is inserted over the wire into the needle. A Bentson or standard J wire is
inserted through the microsheath into the lumen of the aorta. If the stenotic lesion involves
 14b.5 ­Endovascular Revascularizatio 251

the iliac artery, some maneuvering with a torque device may be necessary to traverse the
lesion. A left anterior oblique is useful to image the right iliac bifurcation or vice versa for
the other side. The microsheath is then substituted over the wire for a larger sheath, often
a 5Fr or 6Fr. A pigtail catheter is inserted through the sheath over the wire into the aorta,
and after removing the wire, an aortogram is performed to identify the iliac lesion.
To treat the contralateral limb infrainguinal lesion, a floppy glidewire or J wire is used,
in conjunction with the pigtail, to gain access to the contralateral side. A multipurpose or
glide catheter is exchanged over the wire, and parked over the contralateral femoral
head. A formal femoral arteriogram is performed with an ipsi-lateral projection to splay
out the profunda and superficial femoral artery (SFA) (i.e. for the left femoral, use a Left
Anterior Oblique (LAO) projection; for the right femoral, use a Right Anterior Oblique
(RAO) projection). The rest of the leg is also imaged with contrast to determine the extent
of disease.
Once the contrast injection identifies the lesion, a stiffer guidewire is ‘buried’ into the
contralateral leg, and once the patient is heparinised systemically, a longer sheath (5Fr or
6Fr) is inserted and parked into the contralateral femoral artery. This gives support to any
subsequent sheath/wire use. A guidewire traverses the stenosis, often with the aid of a
guiding catheter through this longer sheath.
An appropriately-sized balloon is placed across the lesion and dilated to a desired pres-
sure to reopen the stenotic lesion by compression the atherosclerotic lesion into the wall of
the artery. Repeat inflation or stenting is appropriate for residual stenosis or flow-limiting
dissection.
The predominant atherosclerotic disease burden in diabetic patients involves the distal
tibial arteries, which are often occluded. Sub-intimal angioplasty is well-described in treat-
ing long tibial occlusions in multiple vessels. A controlled arterial dissection is deliberately
created in a disease-free plane, creating a new ‘lumen’ for blood flow. This sub-intimal
plane is often created by a loop in a hydrophilic guidewire, with the support of a catheter.
After ensuring re-entry into the true lumen by angiography, the dissection plane is angio-
plastied, creating a disease-free lumen, and if necessary, stented.
The tibial vessels require stiffer, steerable 0.14 and 0.18 wires. In addition, low-profile
support catheters and over-the-wire balloons of various sizes need to be available. Complete
total occlusion re-entry devices often need to be used. Drug-eluting balloons are also an
option to prevent restenosis in certain target lesions (Figure 14b.2).
Conventional methods of crossing lesions, especially in the tibial arteries, fail in approxi-
mately 10–20% of attempts. In 1990, Iyer et al. [12] described the pedal access technique
where attempts to recanalise the occlusion is made from direct pedal access. The groins and
the entire affected leg should be circumferentially prepped. The tibial vessel in question is
visualised by duplex, and using the Seldinger technique, the vessel is accessed retrograde
using a micropuncture technique. Fluroscopy and roadmapping may offer better visualiza-
tion in calcified vessels. Once the wire is threaded, a 4Fr microsheath is passed over the wire.
Cook Medical Inc. (Bloomington, IN) has a dedicated pedal access kit. The patient should be
fully heparinised. Using a catheter and wire (most often a 0.018-in such as the V-18
ControlWire), attempts at crossing the occlusion is made. The wire then needs to be snared
from the CONTRALATERAL common femoral artery access proximally. All interventions
can be made over this ‘body-floss’ wire in the standard technique after the wire is snared.
252 14b Surgery or Endovascular Intervention in Diabetic Peripheral Vascular Disease

below-knee popliteal artery

Posterior tibial artery

peroneal artery

Anterior tibial artery

Figure 14b.2 (a) Tibial disease in a diabetic patient with non-healing ulcers of the foot and
(b) Post-anterior tibial artery angioplasty with a 4 mm balloon.

14b.5.2 Advantages
Endovascular techniques have afforded treatment options to diabetic patients who have
little to no open surgical options due to lack of saphenous vein bypass conduit, comorbid
conditions precluding open surgery, or previously failed open revascularizations. It often
provides simultaneous diagnosis evaluation and therapeutic intervention. Furthermore,
both proximal and distal disease can be treated at the same time, including multiple
tibial vessels, optimizing pulsatile flow to the foot. More importantly, endovascular tech-
niques offer a minimally invasive approach to revascularization which has significant
benefits.
In some situations, endovascular revascularization can be combined with open surgery
as a hybrid technique to optimise restoration of blood flow to the lower extremity. For
example, if a patient has limited venous conduit, a shorter bypass can be performed whilst
an inflow or outflow lesion is treated with an endovascular approach.
 14b.6 ­Result 253

14b.6 ­Results

14b.6.1 Open Vs. Endovascular Revascularizations

The pivotal Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial remains
the only randomised trial comparing open bypass surgery to endovascular revasculariza-
tions for PAD [13]. The large-scale UK study included 452 patients, randomised to either
angioplasty with possible stenting or open surgical bypass. Only 42% of the cohort had DM,
and therefore, most of the interventions were not concentrated within the tibial arteries.
Early limb salvage rates were equivalent across the two groups, but early failures and
repeated interventions were more common in the endovascular group.
Similarly, Dick et al. [14] reported limb salvage rates to be similar across the endovascu-
lar and open surgery group amongst diabetic patients, but the diabetic population required
more frequent re-interventions [15]. A meta-analysis demonstrated primary patency was
superior with bypass (72% vs. 49%, at 3-years) but ultimately, limb salvage rates were no
different at 3-years (82%) [16]. Registries have demonstrated improvement of endovascu-
lar technology including atherectomy, drug eluting stents, etc., that show promise in
increasing patency rates, and ultimately, wound healing, but no randomised trials have
currently validated this [17, 18]. Vein bypass has continued to maintain a high amputa-
tion-free survival rate, even in high-risk patients [19]. Disease severity, diabetes, and tissue
loss consistently portend poorer endovascular outcomes [20, 21].

14b.6.2 Superficial Femoral Artery/Popliteal Artery Revascularization

The SFA and popliteal arteries are frequent targets of endovascular intervention PAD in
DM. Lazaris et al. [22] found a technical success rate of 81% vs. 93% (P = 0.05%) in patients
with diabetes and non-diabetes, respectively. Other studies, in contrast, did not find any
association between diabetes and restenosis rates [23, 24]. Various techniques, including
angioplasty with drug coated balloons, newer atherectomy devices, various types of stents,
etc. have pushed the envelope to treating more extensive disease. Whilst technically doable,
treatment of more advanced disease leads to poorer results. Baril et al. [25] report a 52%
primary and 88% secondary one year patency rates to endovascularly treated occluded SFAs,
revealing a high restenosis rate requiring reinterventions to maintain patency in highly-
diseased segments. Various self-expanding, balloon-expandable, covered and non-covered
stents are available to treat residual stenosis or flow-limiting dissections after angioplasty.

14b.6.3 Tibial Revascularization

Technical success rates for endovascular interventions are worse for tibial arteries [26]
compared to femoropopliteal arteries [27]. In addition, heavily calcified arteries in any
location impede technical success with endovascular techniques. Unfortunately, tibial ste-
nosis and occlusions in calcified arteries are the primary cause of non-healing wounds in
diabetic patients. Werneck et al. [28] demonstrated a 50% recurrence rate of angioplasty-
treated tibial stenosis at 1-year in this vulnerable population, with a yearly limb loss rate of
254 14b Surgery or Endovascular Intervention in Diabetic Peripheral Vascular Disease

approximately 25%. Similarly, another review showed 46% primary patency and 84% limb
salvage rate at 1-year after endovascular tibial intervention [20]. Faglia et al. [29] focused
on over 200 diabetic patients with ischemic foot wounds. Treatment of infrapopliteal angi-
oplasty resulted in a 5.2% amputation rate at 30-days. Sadek et al. [30] treated tibial disease
and found improved secondary patency in patients who underwent multi-level interven-
tions compared to isolated tibial interventions. However, limb salvage rates were compara-
ble between the two groups. Ferraresi et al. [31] studied long-term outcomes of isolated
tibial angioplasty in diabetic patients with critical limb ischemia, resulting in restenosis
rates of 42% at 1-year. As expected, repeat endovascular interventions do not have the same
patency rates as primary intervention, regardless of the vascular bed [32].

14b.7 ­Complications

All interventions, including endovascular, have risk that should always be taken into
­consideration prior to deciding upon direction of management. Open peripheral bypass
morbidity and mortality stem mainly from the risk of general anaesthesia: myocardial
infarction, post-operative stroke, respiratory complications, etc. [33] Access site hemato-
mas, pseuodaneurysms, arteriovenous fistulas, retroperitoneal hematomas, distal emboli-
zation, flow-limiting dissections, and arterial wall perforation are risks in all patients
undergoing arterial endovascular intervention. A review of literature suggests that 4–18%
of patients undergoing angioplasty for PAD will suffer a complication [34, 35].
The diabetic population, moreover, often has a very high incidence of chronic kidney
disease due to diabetic nephropathy, and thus, specific care must be taken to prevent
nephrotoxicity with contrast usage. In addition, diabetic drugs such as metformin react
with contrast to create lactic acidosis and should be held prior to any angiogram for at least
48 hours prior and 48 hours after.
Performing endovascular interventions prior to open surgical bypass can significantly
alter the course of limb salvage strategies. For example, the distal target of a bypass after a
failed endovascular option may shift to a more distal target, lowering long-term patency
[36]. In addition, cross-over to bypass surgery from a prior endovascular primary interven-
tion in the BASIL trial demonstrated poorer outcomes than patients who did not have prior
endovascular interventions [37]. This finding can be attributed to more advanced disease
that could not be safely treated by endovascular means in the first place, and other studies
show no influence of clinical success in limb salvage by the choice of initial revasculariza-
tion [14], but still this caveat warrants consideration to the ‘endovascular first’ paradigm.

14b.8 ­Conclusion

PAD affects a significant number of patients suffering from DM, causing profound
morbidity, increased mortality, and significant health care cost. The infrapopliteal pat-
tern of atherosclerosis in diabetic patients has historically been treated with surgical
bypass. The modern era of endovascular surgery now offers a minimally invasive
­alternative to open surgical revascularization – a particularly attractive option in this
  ­Reference 255

population at high-risk for cardiovascular events, poor wound-healing, and dysfunc-

tional status of limbs. Although endovascular interventions may result in limb salvage
rates that are similar to open bypass, high re-intervention rates are often required to
maintain patency. A case-by-case ­revascularization strategy is recommended, incorpo-
rating knowledge of both types of interventions, based on a patient’s individual risk
profile. Diabetic patients with PAD gain the most benefit, not only from technical suc-
cess of surgical intervention, but from mitigating all of their systemic risks from a
multi-disciplinary approach [38].

R
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 259

15

Inpatient Diabetic Foot Care

A UK Perspective
Gerry Rayman
The Diabetes Centre, Ipswich Hospital, Ipswich, UK; University of East Anglia, Norwich, UK and University of Suffolk, Ipswich UK

KEY POINTS
1) Foot complications are the commonest diabetes specific reason for admission to hospital.
2) In England, one quarter of the total cost of diabetes foot disease relates to hospital
admissions.
3) Foot ulceration accounts for 85 % of inpatient spend on foot disease and amputation only 15 %.
4) In England and Wales, the NaDIA, DiabetesUK ‘Putting Feet First’ and NICE guidelines have
been instrumental in setting standards and benchmarking hospitals inpatient diabetes foot
services.
5) The key standards are the presence of Multidisciplinary Diabetes Foot Services in all acute
hospital settings, referral of foot disease to this service within 24 hours, and foot screening of
all admissions with diabetes.
6) In England and Wales, the NaDIA has been instrumental in raising the awareness of inpatient
diabetic foot disease, identified hospitals where there is need for investment into
Multidisciplinary Diabetes Foot Services, and has been associated with a significant improve-
ments in standards of care and reductions in hospital acquired foot lesions.

15.1 ­Introduction

Diabetic foot disease is one of the most feared complications of diabetes because of its
impact on quality of life, family, and socio-economic status. For health care systems, there
is high financial impact, the extent of which being increasingly recognised. Within the
hospital setting diabetic foot disease is the commonest reason for a diabetes specific admis-
sion and the most costly, partly because of the associated excessive length of inpatient stay.
This Chapter, which largely draws from United Kingdom experience, considers the bur-
den and cost of inpatient diabetes foot disease and using nationally collected data reviews
the progress towards achieving recommended standards of inpatient foot service provision
and the impact of initiatives to improve inpatient foot care. The surgical care of inpatients
with foot disease is not considered as this is addressed in other chapters.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
260 15 Inpatient Diabetic Foot Care

15.2 ­The Burden of Inpatient Diabetes

Although there is increasing awareness in many countries of the importance of robust data
to inform decisions on the allocation of finite healthcare budgets, until relatively recently
the burden of inpatient care of patients with diabetes has received little attention. In the
world’s first National Diabetes Inpatient Audit (NaDIA), in England in 2010 it was a sur-
prise to find that people with diabetes occupied 14.9% of inpatient beds; three times the
prevalence of the condition in the general population [1, 2]. This proportion has increased
year upon year and by 2017 the audit reported that more than one in six beds (17.9%) were
occupied by a person with diabetes. Given this rate of increase, by 2030 the occupancy will
exceed one in four. This has major cost and staffing implications for health care systems.

15.3 ­The Burden of Inpatient Diabetic Foot Disease

The NaDIA has also given us new and valuable insights into the specific burden of diabetic
foot disease and its management in English and Welsh hospitals. Of the 17.9% of hospital
beds occupied by people with diabetes, less than 10% are occupied by patients admitted
specifically for acute or chronic complications of diabetes; the vast majority are occupied by
people with diabetes admitted for other conditions such as fractures, pneumonia, elective
surgery etc. Of diabetes specific admissions, diabetic foot complications are by far the
majority. In England in 2010 it accounted for 44% of such admissions; increasing every year
to 51% in 2017. In the USA, Hicks et al. reported a 20% increase in hospitalisations between
2005 and 2010, and attributed this to a change in practice with there being increasing rec-
ognition of the success of the multidisciplinary foot team and benefits of revascularization
in limb salvage [3]. The same reasons will account for the increase seen in England and
Wales but the ageing population with the associated greater prevalence of peripheral
­arterial disease are also likely to be important factors.
In terms of actual bed numbers, Public Health England (PHE) estimated that in the three
year period between 2014/2015 and 2016/2017, in England with a population of 53 million
and 3.8 million people living with diabetes there were 132 114 inpatient spells for diabetic
foot disease, accounting for 1 730 072 bed days [4]. However, this is a considerable underes-
timate as only those where the primary admission diagnosis was diabetic foot disease were
included. Kerr, using Hospital Episodes Statistics data found 96 497 inpatient admissions
with diabetes and foot ulcer or amputation codes in the single year of 2014–2015 [5]. In
2017 the NaDIA, found that patients admitted for diabetic foot disease accounted for 4.3%
of all diabetes related beds, 4.9% were admitted for other conditions but also had active foot
disease, and another 3.1% did not have active foot disease but had a history of previous foot
disease. Thus, over 13% of all the inpatients with diabetes have active foot disease or a
­history of previous foot disease and require either prompt input from specialists in diabetic
foot disease and/or interventions to protect their feet from injury whilst in hospital. Of note
in some countries, admissions for foot disease far exceed these figures. In Barbados where
there is a high prevalence of diabetes, Taylor reported that 42.5% of all inpatient beds were
occupied by people with diabetes, 30% of whom had been admitted for a specific diabetes
complication with foot disease accounting for 89% of these admissions [6].
 15.4 ­Recommended Foot Care for Inpatients with Diabete 261

In Chapter 2, Kerr, estimates the total cost of diabetic foot disease in 2015 to be £1.3 ­billion
($1.7 billion) of which approximately a quarter is related to hospital admissions for diabetic
foot disease; £322 million ($429 million) per year. PHE estimated that during the three year
period previously referred to there were 7300 major amputations in England, giving an age
and ethnicity standardized rate of 8.2 major amputations per 10 000 population-years.
Although amputation is high in the minds of patients and clinical staff, Kerr found that it
only accounted one eight of the inpatient cost, £44 million ($59 million); the predominant
inpatient cost being for ulceration, £278 million ($370 million). The figures from England
contrast strongly with those from a recent Brazilian study [7]. For a population of 210 million,
almost four times greater than England, the estimated total costs for all diabetic foot disease
in 2014 was $361 million, one twentieth of the cost per head of population compared with
England. Furthermore, hospitalisations for diabetic foot disease was estimated at only
$27 721 039; one sixtieth of the cost per head of population in England. The authors believe
that hospital costs were underestimated by a factor of at least 10 but it is also very likely that
there are very significant differences in costings for outpatient and inpatient attendances and
procedures, which may account also for some of the difference. Nevertheless, the fact that a
quarter of the cost of diabetic foot disease in England is for inpatient care and only a 7% in
Brazil suggests there are also likely to be very significant differences in practices.

15.4 ­Recommended Foot Care for Inpatients with Diabetes

15.4.1 Multidisciplinary Foot Services

In 2010 NaDIA found that 39% of acute hospitals did not have a multidisciplinary foot
­service (MDFS) for inpatients with diabetic foot disease and 34% did not even have a podi-
atrist for inpatients with diabetes. Recognizing the rapidity at which diabetic foot disease
can progress, the charity DiabetesUK in their ‘Putting Feet First’ document recommended
that all patients admitted with diabetic foot disease be assessed within 24 hours of admis-
sion by a member of the MDFS for a management plan to be promptly put in place [8].
The National Institute for Health and Care Excellence in England endorsed this in their
guideline document CG119 in 2012 and in a more comprehensive updated guideline
NG19 in 2015 [9]. The management plan should ensure that those needing one or more of
a combination of rapid access to vascular services, immediate antibiotic treatment, and
prompt surgical drainage and debridement are fast tracked to these services.
In the 2010 NaDIA only 50% of patient were seen within 24 hours of admission by the
MDFS. In the 2017 NaDIA, this had increased fractionally to 58%, despite the ‘Putting Feet
First’ campaign and NICE guidance. Furthermore 20% of acute hospitals were still without
a MDFS, and 32% were without an inpatient podiatric service.

15.4.2 Simple Foot Examination on Admission

The ‘Putting feet first’ and NICE guidelines also recommend that every patient with ­diabetes
admitted to hospital irrespective of the reason for admission should have a foot examination
on admission. The purpose being severalfold. Firstly, to detect new or existing foot lesions to
262 15 Inpatient Diabetic Foot Care

ensure prompt referral to the MDFS, and secondly to detect lesions that may be relevant to the
presenting medical condition. For example, it is not unknown for patients to present with septic
shock, endocarditis, spinal, or a cerebral abscesses as a complication of a undetected foot infec-
tion such as osteomyelitis in a toe. A visual inspection is also essential in patients unable to give
a foot history such as those who are confused, or those unaware that they have foot ulceration/
infection as a result sensory loss and/or impaired vision to ensure are prompt attention.
Hospital-acquired pressure ulcers are associated with significant morbidity and mortality
and are a major financial burden. People with diabetes are known to be at increased risk of
pressure ulceration and a recent meta-analysis reported the relative risk ratio at all skin
sites combined to be 1.17 (95% CI 1.02 to 1.36) [10]. Given the frequency of neuropathy and
peripheral arterial disease, it is reasonably assumed that the feet are at even greater risk, but
only recently has this been demonstrated. In a large inpatient population, Wensley et al.
found that compared to those without diabetes the relative risk ratio, after adjusting for
major risk factors and confounders, was 2.24 (CI 1.80 to 2.69) [11]. This is almost double
that at all skin sites reported in the previously mentioned meta-analysis [10]. Given these
risks, it is surprising that diabetes receives little mention in the latest guidance on preven-
tion of pressure ulceration from the National Institute for Health and Care Excellence (CG
179) and from the American College of Physicians [12, 13]. Furthermore, none of the com-
mon generic risk scoring systems which include the Barlow, Braden, Norton, and Waterlow,
specifically includes diabetes as a risk factor [14–16]. The ‘Waterlow’ Score, the most widely
used, lists neurological deficit as a risk factor and mentions diabetes only in this limited
context. Since nurses do not usually examine for neuropathy or peripheral vascular disease,
the detection and protection of those at risk relies on admitting doctors undertaking a foot
examination and the nurses scrutinizing the notes for documentation of those with absent
pulses or loss of protective foot sensation. In reality, this seldom happens.
The actual extent of this harm was for the first time fully appreciated in the 2010 NaDIA
when it was found that 2.2%, more than 1 in 50 of the inpatient population with diabetes
had developed a foot lesion whilst in hospital. As a result ‘Putting feet First’ and NICE
guidelines on diabetic foot disease recommend that all patients should have a simple foot
examination on admission to detect those at risk so that preventative measures can be tar-
geted at them. Unfortunately, despite guidance, in the 2017 NaDIA only 36.8% of patients
notes had documented evidence of a foot examination having been performed. Although
an improvement from the dismal figure of 27.2% in 2010 this remains disappointingly poor.
On the positive side the NaDIA findings have undoubtedly increased the awareness of the
risk and in 2017, 86.3% of hospitals had reported introducing some form of admission dia-
betic foot screening. Furthermore, there has been a very significant reduction in hospital
acquired foot ulceration from 2.2% in 2010 to 1.0% in NaDIA 2017. It is quite possible that
more foot inspections and examinations are being performed but not being recorded.

15.5 ­Summary

As described in this chapter, there has been a concerted effort to improve the outcomes of
people with diabetic foot disease in the United Kingdom. Understanding the economic
burden, and identifying the variations in resources, structures of care and outcomes of
 ­Reference 263

those with diabetic foot disease has been instrumental in making the case for change and
for influencing the development of guidance and standards of care. Having a national
health system and in England and Wales with established systems for auditing has been
essential to this. Benchmarking against others and oneself in yearly audit cycle is an impor-
tant driver for change. Only through such a national audit process can the success of
nationwide programmes be evaluated.
Although there have improvements in service delivery and outcomes, including greater
number of hospitals with MDFS and reductions in harm related to hospital acquired foot
lesions, there is still significant variation in care across the nations. Recognizing this, in
2017, NHS England released ‘transformation’ funds to support the staffing of MDFS in
those hospitals without these services. The provision of such services in other countries is
unknown.

­Disclosures

The author does not report any conflict of interest.

­References

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2 Public Health England: Diabetes Prevalence Model. https://assets.publishing.service.gov.
uk/government/uploads/system/uploads/attachment_data/file/612306/
Diabetesprevalencemodelbriefing.pdf.
3 Hicks, C.W., Selvarajah, S., Mathioudakis, N. et al. (2014 Nov). Trends and determinants of
costs associated with the inpatient care of diabetic foot ulcers. J. Vasc. Surg. 60 (5):
1247–1254.
4 Public Health England: Diabetes. https://fingertips.phe.org.uk/profile/diabetes-ft.
5 Kerr, M.; Chapter 2.
6 Taylor, C.G. Jr., Krimholtz, M., Belgrave, K.C. et al. (2014 Aug). The extensive inpatient
burden of diabetes and diabetes-related foot disease in Barbados. Clin. Med. (Lond.) 14 (4):
367–370.
7 Toscano, C.M., Sugita, T.H., Rosa, M.Q.M. et al. (2018 Jan). Annual direct medical costs of
diabetic foot disease in Brazil: a cost of illness study. Int. J. Environ. Res. Public Health 15
(1): 89.
8 DiabetesUK. Putting Feet First. Commissioning specialist services for the management and
prevention of diabetic foot disease in hospital. http://www.footindiabetes.org/media/
FDUK/PuttingfeetfirstJun09FINAL.pdf.
9 NICE ng19. Diabetic Foot Problems: prevention and management www.nice.org.uk/
guidance/ng19.
10 Liang, M., Chen, Q., Zhang, Y. et al. (2017). Impact of diabetes on the risk of bedsore in
patients undergoing surgery: an updated quantitative analysis of cohort studies. Oncotarget
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11 Wensley, F., Kerry, C., and Rayman, G. (2018 Jul 9). Increased risk of hospital-acquired
foot ulcers in people with diabetes: large prospective study and implications for practice.
BMJ Open Diabetes Res. Care 6 (1): e000510.
12 (2014). Pressure ulcers: prevention and management of pressure ulcers [article online].
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management-of-pressure-ulcers-pdf (accessed 14 Jun 2017).
13 Qaseem, A., Mir, T.P., Starkey, M., and Denberg, T.D. (2015). Risk assessment and
prevention of pressure ulcers: a clinical practice guideline from the American College of
Physicians. Ann. Intern. Med. 162: 359–369.
14 Pancorbo-Hidalgo, P.L., Garcia-Fernandez, F.P., Lopez-Medina, I.M., and Alvarez-Nieto, C.
(2006). Risk assessment scales for pressure ulcer prevention: a systematic review. J. Adv.
Nurs. 54: 94–110.
15 Braden, B.J. and Bergstrom, N. (1994). Predictive validity of the braden scale for pressure
sore risk in a nursing home population. Res. Nurs. Health 17: 459–470.
16 Waterlow, J. (1985). Pressure sores: a risk assessment card. Nurs. Times 81: 49–55.
 265

16

Diagnosis and Management of Infection

in the Diabetic Foot
Edgar J.G. Peters1 and Benjamin A. Lipsky2,3
1
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Internal Medicine, Amsterdam Infection & Immunity
Institute, Amsterdam, The Netherlands
2
Department of Medicine, University of Washington, Seattle, WA USA
3
Green Templeton College, University of Oxford, Oxford, UK

16.1 ­Introduction

Infections of the foot are common in persons with diabetes mellitus, occurring in up to 7%
yearly in tertiary foot clinics [1, 2]. Of note, the incidence of diabetic foot infections (DFI)
appears to have decreased in hospitalized persons with diabetes in the last two decades [3].
A foot ulcer usually serves as a point of entry for the pathogens that cause DFI. Infection
can spread contiguously to involve underlying tissues, including bone, especially if some
degree of peripheral arterial disease is present. Thus, a DFI often triggers a cascade that
eventuates in lower extremity amputation (LEA) [4]. It is important that clinicians
­recognize DFI as soon as possible, as unchecked infections are responsible for about 60% of
all LEAs in developed countries [5]. Appropriate management of DFI will not only spare
limbs, but can reduce financial costs as well [3, 6, 7]. There have recently been a number of
guidelines and systematic reviews that serve as a basis for this chapter [8–11].

16.2 ­Pathophysiology of Infections in Persons

with Diabetes Mellitus
The reasons for the documented increased risk and severity of infections in persons with
diabetes are unclear. In‐vitro studies have demonstrated adverse effects of metabolic distur‑
bances, including hyperglycemia, on the immune system. Diabetes appears to have multi‑
factorial effects on various parts of the immune system, especially on the cells that mediate
innate immunity. This response consists of local vasoactive and (pro)‐inflammatory
cytokines, the complement system, and cells capable of phagocytosis, i.e., ­polymorphonuclear
cells (PMN) and monocytes.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
266 16 Diagnosis and Management of Infection in the Diabetic Foot

Locally vasoactive cytokines (e.g., bradykinins) cause vasodilatation through the nitric‐
oxide (NO) response. In hyperglycemia, however, the dysregulation of the NO response can
instead lead to vasoconstriction, which in turn can result in hypoxia and to impaired influx
of phagocytes [12, 13]. Pro‐inflammatory cytokines are elevated in hyperglycemia, which
can result in increased insulin resistance, leading to further elevations of pro‐inflammatory
cytokines [14]. In the presence of hyperglycemia, the complement system can be either
activated or inhibited [15–17].
In persons with diabetes, PMNs and monocytes appear to have multiple impairments,
including in chemotaxis, adherence, phagocytosis, and intracellular killing [18]. In vivo
tests have shown that these functions can be normalized by insulin treatment [19]. While a
systematic review of controlled trials on the effectiveness of granulocyte colony stimulat‑
ing factor (G‐CSF) in DFI reported that it had no apparent effect on resolution of infection
or healing of the foot ulcer, there was a modest reduction in the need for surgical interven‑
tions (including LEAs) and a shorter duration of hospitalization [20].
The adaptive immune system, i.e., T‐cells and immunoglobulins, seems less affected by
diabetes than the innate system. Nevertheless, vaccination studies have demonstrated
some specific defects in the cellular adaptive immune system in patients with type 1 diabetes,
regardless of glycemic control [21, 22].

16.3 ­Risk Factors for DFI

Risk factors for DFI have been examined in a few studies. A prospective, multicenter study
of persons with diabetes compared 150 patients with a foot infection (including osteomy‑
elitis in 20% of cases) with 97 who did not develop a foot infection [23]. Factors associated
with developing a foot infection were a: wound that extended to bone (based on a positive
probe‐to‐bone test, odds ratio [OR] 6.7); foot ulcer with a duration >30 days (OR 4.7); his‑
tory of recurrent foot ulcers (OR 2.4); wound of traumatic etiology (OR 2.4); and, the pres‑
ence of peripheral vascular disease (OR 1.9). Only one infection occurred in a patient
without a previous or concomitant foot ulcer.
A multivariable regression analysis from a population‐based retrospective cohort study of
over a million discharges for DFI (including 15% with osteomyelitis) found that peripheral
vascular disease (OR 2.9), peripheral neuropathy (OR 2.6), male sex (OR 1.7), hospital
discharge from the Midwest region in the USA (OR 1.3), and undergoing renal dialysis (OR
1.3) had the strongest associations with DFI [3]. Another retrospective review of 112 patients
with a severe DFI found by multivariate analysis that associated factors were: a previous
amputation (OR 19.9); peripheral vascular disease (OR 5.5); or, peripheral sensory
neuropathy (OR 3.4) [24]. Other non‐controlled studies have identified renal insufficiency
and renal transplantation [25] and walking barefoot as risk factor for DFI [26].

16.4 ­Clinical Signs and Symptoms

Both the International Working Group on the Diabetic Foot (IWGDF) and of the
Infectious Diseases Society of America (IDSA) recommend basing the diagnosis of
DFI on clinical findings [8, 11]. Although classical clinical signs and symptoms of
 16.5 ­Classificatio 267

i­ nflammation, i.e., ­redness, warmth, induration, pain/tenderness, and loss of function,

are somewhat subjective, both clinical experience and some published data support
their usefulness (see Table 30d.1). Of note, the presence of peripheral neuropathy, limb
ischemia or the immunological ­perturbations noted above may reduce the clinical
­evidence of inflammation [27]. Because of these limitations, some authorities have sug‑
gested adding the presence of alternative findings to the diagnosis of infection, e.g.,
purulent or non‐purulent discharge, fetid odor, necrosis, undermining of wound edges,
poor granulation tissue and lack of wound healing [28, 29].
Even in severe infections, systemic inflammatory signs of sepsis (e.g., fever, hypotension,
delirium, leukocytosis) are often absent. When present, however, these findings indicate
that the infection is severe [8, 11, 30, 31]. The presence of clinically significant ischemia to
the affected foot often increases the severity of the infection [29]. Since all open wounds are
colonized with bacteria, microbiological data by themselves do not contribute to the
­diagnosis of infection. Microbiological data are, however, necessary to determine the
appropriate selection of antimicrobial therapy.

16.5 ­Classification

Several classification schemes are available to help assess the diabetic foot ulcers (DFU).
These typically have a subsection of describing infection, but in almost all it merely states
its presence or absence. Examples of DFU classification schemes include the Meggit‐
Wagner, [32], SAD/SAD and SINBAD [33, 34], University of Texas (UT), [34–36] Wound
Severity Score, [37] the DUSS and MAID [38, 39], the Diabetic Foot Infection (DFI) Wound
Score [40, 41] and Wound, Ischemia and foot Infection WIfI [42]. While there is no clear
evidence that any of these classification systems or wound scores is better than another,
WIfI is becoming the most used. The only systems that attempt to quantify the severity of
infection are PEDIS (IWGDF), IDSA, and S(AD)/SAD; these offer more detail to describe
infection and provide a semi‐quantitative four point severity scale.
Adequate assessment of infection severity helps to determine appropriate empirical ther‑
apy. The schemes developed by the IDSA and the IWGDF more clearly define infection and
levels of severity, thus helping guide therapy [8, 11]. The PEDIS ulcer classification (which
stands for perfusion, extent [size], depth [tissue loss], infection, and sensation [neuropathy])
[8] was originally developed by the IWGDF for research purposes, but can be used for clinical
practice as well. [43] The infection part of PEDIS and the IDSA classification both have a
semi‐quantitative gradation of ulcer severity and differ mostly in minor details (see Table 30d.1)
[11]. One substantial difference is that 2019 update of the IWGDF infection classification
moved “osteomyelitis” as a separate category (designated [O]), rather than part of grade 3.
A major advantage of both classifications is that their analogy with classifications of other
infections makes them easy for clinicians to understand and remember. Importantly, the sys‑
tem has been validated by use in prospective studies of diabetic patients [44–46], significantly
predicting the need for and duration of hospitalization and likelihood of LEA [44].
Because the full PEDIS classification was designed to include all types of foot ulcers, it
was relatively complicated and hard to remember. In one study, the system was used for
a comparative audit among 14 European diabetic foot centers [45]. Another study investi‑
gating procalcitonin and C‐reactive protein found that they may be useful in distinguishing
268 16 Diagnosis and Management of Infection in the Diabetic Foot

mildly infected from non‐infected diabetic foot ulcers [46]. Classification of DFI into
moderate versus severe has shown this distinction to be correlated with important
clinical outcomes [47].

16.6 ­Microbiology

As with other infections, the results of microbiological tests from diabetic foot wound
­specimens must be interpreted with reference to the clinical situation. All open wounds
are to some extent colonized with bacteria. The results of any microbiological analysis
­technique can be misleading, including Gram‐stain smear, phenotyping with classic
­cultures, or genotyping with modern molecular methods. Identified organisms often
­represent colonizing (transient or resident) flora, but may also include potentially path‑
ogenic agents. Treating a patient with a colonized wound without clinical infection with
antimicrobials has not been shown to either prevent infection or to improve ulcer heal‑
ing [48, 49]. It can, however, lead to adverse effects, including hastening development of
antimicrobial resistance, Clostridioides difficile associated diarrhea, and increased
financial costs.
Selecting an optimal antibiotic regimen is best determined by obtaining appropriate
specimens for microbiological analysis. The use of proper sampling techniques (after
debridement, from deep, non‐necrotic, tissue taken through non‐colonized surround‑
ings, or of pus) is critically important for identifying the true pathogens and helping to
avoid colonizing organisms. Superficial cultures obtained with swabs may be easily col‑
lected, but are less reliable than cultures of tissue obtained by biopsy or curettage [50].
Results of a large, well‐designed trial found that for infected DFU, cultures of tissue spec‑
imens are both more sensitive and specific than those of swabs. Most previous studies
found swab specimens grow more isolates (likely contaminating or colonizing flora) than
aseptically obtained deep tissue specimens [7]. In particular, studies of patients with dia‑
betic foot osteomyelitis have generally found that cultures of bone specimens do not cor‑
relate well with those of superficial swabs, [51, 52]. Although they correlate better with
cultures of deep wound specimens, [53] cultures of bone remain the best source of micro‑
biological information.
In patients not recently exposed to antimicrobial treatment, mild infections are usually
caused by aerobic gram‐positive cocci, predominantly Staphylococcus aureus and, to a lesser
degree, beta‐hemolytic streptococci [54, 55]. Coagulase‐negative staphylococci are common
isolates; while they are most often colonizers or contaminants, they may be true pathogens,
especially when isolated from tissue or bone specimens. Recent studies from developing
countries have reported isolation of S. aureus less commonly than in developed countries
(30% vs. 75%) [56, 57]. Deep wounds with more severe infections, especially in previously
antibiotic‐treated patients, usually grow polymicrobial flora with mixed gram‐positive cocci,
Enterobacteriaceae, sometimes non‐fermentative gram‐negative rods (e.g., Pseudomonas)
and obligate anaerobes (e.g., Peptostreptococcus, Finegoldia, Bacteroides) [54, 58]. In Western
countries, infection with Pseudomonas aeruginosa is relatively uncommon, except in those
treated with antibiotics, in cases of deep puncture wounds, in warmer climates, or in
patients whose feet are frequently exposed to water [54]. Obligate anaerobes, when isolated,
 16.7 ­Treatmen 269

are almost always part of a mixed infection with aerobes and typically found in ischemic or
necrotic wounds [59]. The most commonly isolated microorganisms from DFIs in selected
clinical circumstances are summarized in Table 16.1.
Infections caused by unusual and resistant flora may not respond to empirically selected
antimicrobial therapy [60, 61], which may not cover multidrug‐resistant organisms (MDROs),
e.g., methicillin‐resistant S. aureus (MRSA), vancomycin‐resistant Enterococcus (VRE),
extended‐spectrum β‐lactamase (ESBL) producing Enterobacteriaceae [62]. Identified risk fac‑
tors for antibiotic‐resistant bacteria in DFI include: previous antibiotic therapy, especially of
long duration; recurrent hospitalizations for the same ulcer; longer duration of hospital stay;
and, the presence of underlying osteomyelitis [60, 63]. Studies of the outcome of ulcers infected
with MDROs have produced conflicting results [56, 60, 64, 65]. Worse outcomes can some‑
times be explained by confounding factors, such as patients colonized with MRSA have more
often had previous unsuccessful treatments or hospitalizations that led to the colonization
with resistant organisms. Furthermore, most specimens for culture in studies reporting a poor
outcome with MRSA in were superficial swabs, rather than tissue. This might also explain why
most of the patients whose infection resolved despite cultures with MDROs healed without
antimicrobial drugs specifically targeted at these bacteria [66]. A review that posed the ques‑
tion of whether DFI with MRSA differ from those of other pathogens concluded that, notwith‑
standing the substantial limitations of the available literature, there did not appear to be a need
for any special treatment for DFI caused by MRSA [67].
The incidence of MRSA DFI, while increasing in the past couple of decades, now seems
to be decreasing [61, 65, 68]. However, the increase in the past decades of MRSA isolates
with reduced susceptibility to vancomycin is a further concern. ESBL‐producing and
­carbapenemase‐producing Enterobacteriaceae are an emerging international problem,
including in DFI [56].

16.7 ­Treatment

16.7.1 Uninfected Ulcers

Published trials have not found that systemic antibiotic treatment of a wound without
clinical infection is effective in either improving healing of ulcers or as prophylaxis against
infections [49]. Some favor providing antibiotic treatment for clinically uninfected wounds
in the belief that high levels of surface colonization (‘bacterial bioburden’) may inhibit
healing or that overt signs of infection are obscured in persons with diabetes [48, 69].
Given the lack of evidence of efficacy and the known potentially adverse clinical,
microbiological and financial effects of antibiotic therapy, current guidelines discourage
prescribing systemic antibiotics for clinically uninfected wounds [8, 11, 70]. These
wounds, of course, do need other forms of treatment, such as careful debridement,
appropriate offloading and sometimes revascularization.

16.7.2 Infected Ulcers

Systemic antimicrobial therapy is necessary, but by itself not sufficient, to cure most infections.
Antibiotics must be combined with appropriate debridement, pressure off‐loading, and
Table 16.1 Suggestions for empiric antibiotic regimens for DFIs, based on the IDSA guidelines [8, 10, 11].
Infection severity
Mild (usually treated with
oral antibiotics)
Moderate (oral, or initial
parenteral antibiotics) or
severe (usually treated with
parenteral antibiotics)
Likely pathogen Antimicrobial agent Comment
S. aureus (MSSA), Dicloxacillin or flucloxacillin QID dosing; narrow spectrum, inexpensive
Streptococcus spp. Clindamycin Most gram‐positives, anaerobes. Usually active against
community acquired MRSA (but consider ordering a D‐test
before using). Inhibits protein synthesis of some toxins
Cephalexin QID dosing; inexpensive
Levofloxacin Once‐daily dosing; suboptimal against S. aureus
Amoxicillin/clavulanate Relatively broad‐spectrum oral agent, includes
anaerobic coverage
MRSA Doxycycline Active against many MRSA and some gram‐negative
organisms; uncertain against Streptococcus spp.
Trimethoprim/sulfamethoxazole Active against MRSA and some gram‐negatives.
Uncertain activity against Streptococcus spp.
MSSA, Streptococcus spp., Levofloxacin Once‐daily dosing, suboptimal against S. aureus
Enterobacteriaceae,
obligate anaerobes
Cefoxitin Second‐generation cephalosporin with anaerobic
coverage
Ceftriaxone Once‐daily dosing, third generation cephalosporin
Ampicillin‐sulbactam Adequate if low suspicion of P. aeruginosa
Moxifloxacin Once‐daily oral dosing. Relatively broad‐spectrum,
including most
obligate anaerobic organisms (but not Pseudomonas).
Ertapenem Once‐daily dosing. Relatively broad‐spectrum including
anaerobes, but not active against P. aeruginosa or enterococci
 Tigecycline Active against MRSA. Spectrum may be excessively broad
(but no coverage of P. aeruginosa). High rates of nausea and
vomiting, worse outcomes than comparators and increased
mortality warning make this a lower choice agent
Levofloxacin or ciprofloxacin Limited evidence supporting clindamycin for severe
with clindamycin S. aureus infections; PO & IV formulations available for
both drugs
Imipenem‐cilastatin Very broad‐spectrum (but not against MRSA); use only
(meropenem; doripenem) when this is required. Consider when ESBL‐producing
pathogens suspected

MRSA Linezolid (tedezolid) Increased risk of toxicities when used for >2 weeks
Daptomycin Once‐daily dosing. Requires serial monitoring of CPK
Vancomycin Vancomycin MICs for MRSA are gradually increasing;
required serum level monitoring

Pseudomonas Piperacillin‐tazobactam TID/QID dosing problematic. Useful for broad‐spectrum

aeruginosa coverage. P. aeruginosa is an uncommon pathogen in
diabetic foot infections except in special circumstances

MRSA, Vancomycina, ceftazidime, Very broad‐spectrum coverage. Usually only used for empiric
Enterobacteriaceae, cefepime, piperacillin/ therapy of severe infection. Consider addition of obligate
Pseudomonas, and tazobactam, aztreonam, or a anaerobe coverage if ceftazidime, cefepime, or aztreonam
obligate anaerobes carbapenem selected

Relatively narrow‐spectrum agents (e.g. vancomycin, linezolid, daptomycin) should be combined with other agents (e.g. a fluoroquinolone) if polymicrobial
infection (especially moderate or severe) is suspected.
Use an agent active against MRSA for patients who have a severe infection, evidence of infection or colonization with this organism elsewhere, or epidemiological
risk factors for MRSA infection.
Select definitive regimens after considering the results of culture and susceptibility tests from wound specimens, as well as the clinical response to the empiric regimen.
Similar agents of the same drug class can probably be substituted for suggested agents.
Some of these regimens do not have FDA approval for diabetic foot or skin and skin structure infections.
Abbreviations: CPK, creatine phosphokinase; ESBL, extended‐spectrum β‐lactamase; FDA, US Food and Drug Administration; IV, intravenous; MIC, minimum
inhibitory concentration; MRSA, methicillin‐resistant S. aureus; MSSA, methicillin‐sensitive S. aureus; PO, oral; QID, four times a day; TID, three times a day.
a
Daptomycin or linezolid may be substituted for vancomycin.
272 16 Diagnosis and Management of Infection in the Diabetic Foot

frequently one or more surgical procedures. Peripheral edema requires leg elevation and com‑
pression of the limb. Surgical interventions range from minimal debridement (cleansing,
removal of callus and necrotic material, necessary in all diabetic foot ulcers), through incision
and drainage of purulent collections and resection of devitalized tissue, to bone resections,
revascularization and various levels of LEA. Surgeons performing these operations must have
adequate knowledge of basic anatomical concepts of the foot, especially the various compart‑
ments. Optimally, medical and surgical clinicians should work together to decide when surgery
is needed and what type of procedure is most appropriate [71, 72]. Patients with severe arterial
insufficiency may require revascularization, either by an endovascular or open procedure. In
selected cases, one of the adjunctive treatments described below may be useful.

16.7.2.1 Antimicrobial Therapy

Most initial antibiotic therapy is empiric, i.e., initiated without proof of the causative
pathogen(s). Assessment of the severity of infection is important in determining the most
appropriate antibiotic agents and route of treatment [8, 11, 73]. After the results of appro‑
priately obtained specimens for culture become available, the clinician can revise and
target treatment. For optimal targeted treatment, clinicians must combine the culture
results with consideration of the patient’s clinical response to the empirical regimen.
Suggested empirical regimens are summarized in Table 16.1 [10, 11]. Because of the limi‑
tations of published data on both topical and systemic antimicrobial therapy, [74, 75]
these recommendations are based predominantly on expert opinion.

16.7.2.2 Comparison of Antibiotic Agents

In 2019 the IWGDF published a systematic review on treatment of DFI [9]. The literature
search identified a total of 15,327 articles, of which 53 were selected for full‐text review.
Among the studies, 42 were randomized controlled trials (of which 7 were published after the
search in the last IWGDF systematic review in 2015), 6 were cohort studies (of which one was
published after 2015), and 3 were case‐control studies (all published after 2015). The included
papers consisted of 16 studies on the use of antibiotics in skin and soft tissue studies, 12 that
included patients with osteomyelitis, seven on treatment with topical antiseptic agents and
five on topical antibiotic therapy, two on alternative or folklore treatments and five on the role
of surgery in DFI. Other studies dealt with various adjunctive treatments and financial
aspects of treatment. Comparisons of different antibiotic regimens generally suggested that
newly introduced antibiotic regimens were as effective as conventional therapy (and also
more cost‐effective in one study), but one study failed to demonstrate non‐inferiority of tige‑
cycline compared with ertapenem. No published data supported the superiority of any par‑
ticular route of delivery of antibiotic therapy in either soft‐tissue infection or osteomyelitis. In
general, achievable serum and tissue levels of antibiotics in studies of patients with DFIs
were adequate [76]. Oral absorption of certain antibiotics (e.g., quinolones, clindamycin,
doxycycline, rifam[pic]in, sulfamethoxazole/trimethoprim) is high enough to make oral
therapy effective, even for diabetic foot osteomyelitis or in patients with diabetic gastropare‑
sis. Results from two studies suggested that early surgical intervention was associated with a
significant reduction in major LEAs, but the methodological quality of each was low. The
relatively few trials, mostly with poor methodological quality, provide no strong evidence for
specific recommendations of a particular antimicrobial regimen to prevent amputation,
 16.7 ­Treatmen 273

resolve infection or shorten duration of ulcer ­healing [9]. A Cochrane systematic review of
antibiotic therapy for DFI similarly concluded that it is not clear if any one systemic antibiotic
treatment is better than others in resolving infection or in terms of safety [75].

16.7.2.3 IWGDF Grade 2 (Mild) Infections

Mild infections (IWGDF grade 2), that have not previously been treated with antibiotics,
are usually caused by staphylococci or streptococci. Outpatient treatment is safe for most
patients who can either care for themselves or have home care available [8, 11]. Wound
specimens from some mild infections might yield gram‐negative rods, but these are usually
(at least in Western countries) secondary colonizers that do not need targeted antibiotic
therapy. Treatment with a semisynthetic penicillin with anti‐staphylococcal activity,
(e.g., flucloxacillin or dicloxacillin), a first‐generation cephalosporin, (e.g., cephalexin)
or clindamycin for one to two weeks is usually appropriate [8, 11]. In locations where,
or for patients in whom, the risk of MRSA infection is high, obtaining optimal wound cul‑
tures is particularly advisable [8, 11]. Antibiotic options for treatment of MRSA infections
include trimethoprim‐sulfamethoxazole (which has only weak anti‐streptococcal activity),
clindamycin (variable MRSA susceptibility), doxycycline (suboptimal for streptococci) or
linezolid (relatively high risk of adverse events). Systematic reviews by both the Cochrane
group and the IWGDF of topical antimicrobial therapy (which might be appropriate for
some mild infections) concluded that data on the effectiveness and safety of topical antimi‑
crobial treatments for diabetic foot ulcers is limited by the availability of relatively few,
mostly small, and often poorly designed trials [74, 77].

16.7.2.4 IWGDF Grade 3 (Moderate) Infections

Patients with a IWGDF grade 3 (moderate) infection, especially those with a chronic or previ‑
ously treated wound, often require broad‐spectrum empiric coverage for both gram‐positive
cocci and gram‐negative rods. In mild to moderate infections, anaerobes are infrequently major
pathogens [78]. When anaerobes are present, they are usually part of a mixed infection. It
remains unclear whether their presence leads to more severe manifestations or they are largely
colonizers associated with the presence of greater degrees of tissue ischemia and necrosis.
Adequate debridement and drainage are key, and in some cases may be sufficient for non‐severe
­infections that lack necrosis or severe ischemia [8, 11]. The IWGDF and the IDSA guidelines
both suggest similar empirical treatment for grade 3 (moderate) and for grade 4 (severe) infec‑
tions [8, 11]. Suggested options include parenteral (at least initially) empirical therapy with a
beta‐lactam antibiotic with anti‐beta lactamase activity (e.g., amoxicillin/­clavulanate or pipera‑
cillin/tazobactam), or a combination of a fluoroquinolone (e.g., ­ciprofloxacin, levofloxacin,
moxifloxacin) with clindamycin. When infection with multi‐resistant gram‐negative organisms
is a concern, a carbapenem (e.g., imipenem) would be an appropriate option, and anti‐MRSA
therapy is recommended when the risk of MRSA infection is high (Table 16.1) [79].
Initially, hospitalization may be necessary for diagnostic or surgical procedures, or paren‑
teral administration of antibiotics. These patients should be observed for their response to
treatment, as inappropriate treatment can lead to more proximal amputations in 10% of
cases [8, 11]. The empirical antibiotic regimen should be adapted to a more targeted therapy
when the results of culture and sensitivity tests become available. For this definitive therapy,
clinicians should aim to cover the most likely pathogens, but target therapy so treatment is
274 16 Diagnosis and Management of Infection in the Diabetic Foot

as narrow in spectrum and short in duration as possible. Duration of therapy depends on

infection severity, clinical response and the need for surgical intervention, but rarely needs
to be more than two to three weeks in case of skin and soft tissue infection [11, 80].

16.8 ­IWGDF Grade 4 (Severe) Infections

The empiric antibiotic treatment for IWGDF grade 4 infections only differs from that for
moderate infections in requiring a lower threshold for covering resistant bacteria and obli‑
gate anaerobes [8, 11, 76]. Intravenously administered antibiotics are most appropriate, as
these infections are potentially limb, and even life, threatening, may harbor a high bacte‑
rial load and can progress quickly. Parenteral therapy is required to rapidly achieve
­adequate serum and tissue levels after presentation, when gastrointestinal absorption may
be impaired [8, 11]. Most patients who show evidence of improving can be switched to oral
antibiotic therapy after a few days. Oral antibiotic therapy is effective, and has the advan‑
tages of being safer, less expensive and easier for patients and medical staff [81].

16.8.1 Adjunctive Treatments

16.8.2 Topical Treatment
Several studies have assessed the effectiveness of topical antimicrobial treatments (e.g.,
silver, mafenide acetate, povidone, or cadexemer‑iodine, hypochlorite, peroxide, zinc
oxide) in patients with infected diabetic foot ulcers, as adjuncts to systemic antibiotic treat‑
ment. None of these have proven to lead to superior outcomes compared to other or stand‑
ard treatment [74, 82]. Non‐antimicrobial effects of these agents on the process of wound
healing are variable. One of the more frequently used types of topical agents are those
containing silver, but systematic reviews have not identified any studies proving its efficacy
for curing infection or improving wound healing. One systematic review identified a study
of maggots (larvae) [82] in patients with peripheral vascular disease that found they were
associated with a decreased use of antibiotics and need for amputations, suggesting a
potential antibacterial as well as ulcer healing effects. Larvae appear to have a direct anti‑
microbial effect and can may also reduce biofilm formation [83]. Although widely used for
wound healing in some centers, there are no published studies on the effectiveness of
negative pressure or vacuum assisted therapy on DFI, including osteomyelitis [8, 82].

16.8.3 Revascularisation
The combination of infection and ischemia is associated with a particularly poor outcomes
in DFIs [45]. Revascularization of an ischemic limb, either with open bypass surgery or
endovascular techniques, is beneficial in several ways, including enabling required debride‑
ment and minor surgery, improving delivery of antibiotics and leukocytes and enhancing
wound healing [8]. There are no published studies to help clearly define when or what type
of vascular surgery should be performed in patients with DFI [9].
 16.9 ­Osteomyeliti 275

16.8.4 Hyperbaric Oxygen Therapy

The potential benefits of hyperbaric oxygen therapy to enhance diabetic foot wound heal‑
ing or to prevent amputation have been much debated [84, 85]. Whatever use it may be for
these indications, there are no published data on any direct beneficial effects of hyperbaric
oxygen therapy specifically on control of infection [9].

16.9 ­Osteomyelitis
16.9.1 Overview
Osteomyelitis is an infection of bone with involvement of bone marrow [8]. In the diabetic
foot these infections usually occur by contiguous spread of microorganisms into bone from
a chronic ulcer. Underlying osteomyelitis occurs in ~50–60% of patients hospitalized for a
DFI, and in ~10–20% of apparently less severe infections presenting in the ambulatory
­setting [8]. Diagnosis is based on clinical, imaging, and especially laboratory (bone culture
and/or histology) evidence. Treatment typically involves prolonged antibiotic therapy,
­usually combined with some surgical resection procedure (sometimes repeated). Infection
of bone greatly increases the likelihood that the patient will require a LEA [23]. The most
common causative pathogen is S. aureus, either alone or as part of a polymicrobial infec‑
tion [52]. Osteomyelitis can be persistent because it is associated with impaired inflamma‑
tory responses, low local leukocyte counts, possibly limited antibiotic penetration and
biofilm formation. Biofilm, comprised of colonies of bacteria in a matrix of hydrated poly‑
saccharides, protein and other molecules, is associated with a slower metabolism and a
lower replication rate of bacteria. Antimicrobials are therefore less effective because of
these metabolic changes in bacteria, as well as their limited penetration in the biofilm
extracellular matrix [86].

16.9.2 Diagnosis
The diagnosis of osteomyelitis is often difficult. Early infection may be missed because it
takes several weeks for the infection to be observable on plain X‐rays. Later infection can be
difficult to distinguish from changes caused by non‐infectious causes, e.g., neuro‐osteo
(Charcot) arthropathy, arthrosis, or gout.

16.9.2.1 Clinical Findings, Including Probe-to-Bone Test

Any chronic ulcer overlying a bony prominence, especially if it is deep and in the presence
of poor peripheral arterial supply, should raise suspicion for underlying osteomyelitis. The
accuracy of a physician’s clinical judgement for the presence of osteomyelitis is surprisingly
good, with a positive likelihood ratio (+LR) of 5.5 and a negative likelihood ratio (−LR) of
0.54 [8]. One clinical procedure, the probe‐to‐bone test, is useful and easy to perform: using
a blunt, sterile, metal probe it is positive if bone is palpable in the base of the wound (hard
gritty structure). A negative probe‐to‐bone test in a patient in whom the pre‐test probability
276 16 Diagnosis and Management of Infection in the Diabetic Foot

of osteomyelitis is low (e.g,. <20%) largely rules out the diagnosis, both in outpatient and
inpatient settings, with a reported negative predictive value of up to 98%. Conversely, in a
patient with a high pre‐test probability (e.g., >50%) a positive result makes the diagnosis of
osteomyelitis likely [87].

16.9.2.2 Laboratory Tests

Many biomarkers have been investigated as diagnostic tests for osteomyelitis [88]. The best
of currently available laboratory tests studied is the erythrocyte sedimentation rate (ESR)
[88]. A result of >70 mm/hour is highly suggestive of osteomyelitis. The ESR is also useful
to monitor the response to treatment. Based on more limited studies, C‐reactive protein,
procalcitonin levels and other inflammatory markers seem less useful.

16.9.2.3 Imaging Studies

Plain radiography. Plain x‐rays, which are relatively inexpensive, widely available and can
be interpreted by experienced foot clinicians, are usually the initial imaging study. Features
characteristic for osteomyelitis on plain X‐rays of the foot are listed in Table 16.2 [8, 10].
The reported sensitivity of plain radiography in osteomyelitis ranges from 28 to 75% [8]. In
contrast to what most clinicians think, conventional radiographic results are only
­marginally predictive of osteomyelitis, with a pooled specificity of 0.68 and sensitivity of
0.54 [89, 90]. Unfortunately, there have been no published studies that examined
­sequentially obtained X‐rays of the foot over time, a widely used diagnostic method. Such
a strategy might be more likely to predict the presence of osteomyelitis than a single series.
Magnetic Resonance Imaging (MRI). Among the advanced imaging techniques, MRI
is generally considered the best of the currently available options for diagnosing osteo‑
myelitis [11]. The characteristic features of osteomyelitis on MRI are: low focal signal
intensity on T1 weighted images; high focal signal on T2 weighted images; increased
signal in short tau inversion recovery (STIR) in bone marrow; and, diverse less specific
changes [11]. In three meta‐analysis on the use of MRI in the diabetic foot, the sensitivity
was 77–100%, the specificity 40–100% [90–92]. The diagnostic OR in the reviews was 24
[91], 37 [92], and 42 [90].

Table 16.2 Characteristic features of osteomyelitis on plain radiography [8, 10].

●● Periosteal reaction or elevation

●● Loss of cortex with bony erosion
●● Focal loss of trabecular pattern or marrow radiolucency
●● New bone formation
●● Bone sclerosis, with or without erosion
●● Sequestrum: devitalized bone with radiodense appearance that has become separated from
normal bone
●● Involucrum: a layer of new bone growth outside existing bone resulting from the stripping off of
the periosteum and new bone growing from the periosteum
●● Cloaca: opening in an involucrum or the cortex through which sequestra or granulation tissue
may be discharged
The bony changes are often accompanied by soft tissue swelling
 16.9 ­Osteomyeliti 277

Nuclear medicine. Several types of nuclear imaging are available and new tracers are
being developed to improve diagnostic accuracy for soft tissue infection and osteomyelitis.
Bone scintigraphy is usually performed with 99mTc‐hexamethylpropyleneamineoxime
[HMPAO], which detects osteomyelitis by an increased intensity in bone [90]. Pooled data
show that bone scans are sensitive (80%), but non‐specific (28%), with even the triple‐phase
bone scan being markedly inferior to MRI [90]. Leukocyte scintigraphy uses radio‐labelled
white blood cells, usually with 99mTc or 111Indium‐oxine. Leukocytes are generally not
taken up in healthy bone, making leukocyte scans more specific for osteomyelitis than
bone scans [93]. The positive predictive value for diagnosing osteomyelitis by leukocyte
scans is 72–90%, and the negative predictive value is 81–83% [90, 93]. Scintigraphy with
99m
Tc has a higher diagnostic OR than leukocyte scintigraphy with 111In [92]. One system‑
atic review suggested that MRI outperforms leukocyte scanning with diagnostic positive
and negative ORs of 120 and 3.4, respectively, [91] but a more recent review found the
opposite, with diagnostic ORs of 37 and 118, respectively [92].
Other available nuclear medicine techniques include 99mTc‐/111In labelled human immu‑
noglobin G (HIG) and anti‐granulocyte antigen monoclonal antibodies and their frag‑
ments. Because 99mTc‐/111In‐HIG uptake is related to vascular permeability and not specific
to inflamed tissue, the specificity is lower than radiolabeled leukocytes [93].
A recent systematic review reported results of studies using computed tomography (CT)
and [18F]‐2‐fluoro‐2‐deoxy‐D glucose (18F‐FDG)‐positron emission tomography (PET)
scans for the diagnosis of osteomyelitis [92]. Based on limited number of studies, 18F‐FDG‐
PET has a reported sensitivity of 89%, a specificity of 92%, and a diagnostic OR of 95 for
diabetic foot osteomyelitis [92].

16.9.2.4 Bone Biopsy

The generally accepted reference standard for the diagnosis of osteomyelitis is the results
of the combination of microbiological culture and histopathological examination of
affected bone [8]. A bone specimen may be obtained either as part of an operative
procedure or percutaneously (optimally through uninfected skin). Proper technique is
important to avoid false positive results when the biopsy is taken through an area of soft
tissue colonization, and false negatives when the area of bone infection is missed [8].
Bone cultures are not needed in all cases of suspected diabetic foot osteomyelitis, but they
are helpful for diagnosis when test results are contradictory or to guide antibiotic therapy
when causative pathogens or their antibiotic susceptibilities are difficult to predict.
Superficial cultures of wound swabs have been found to be identical to those of bone
biopsy in only 22.5% of patients, with the swabs often yielding a larger number of
microorganisms [51, 94]. In one study, fine needle aspiration of deep soft tissue gave the
same result as bone biopsy in only 32% of cases [94]. Where possible, any active antibiotic
therapy should be discontinued (for at least 48 hours and preferably longer) before the
biopsy to maximize the yield from cultures [95, 96]. As osteomyelitis, in the absence of soft
tissue infection, is usually a chronic low‐level infection, it is generally safe to hold
antibiotics for this duration. One apparently useful approach is to start empirical antibiotic
treatment for any overt soft tissue infection, then withhold treatment for two weeks,
perform a bone biopsy and restart treatment for osteomyelitis if it is detected (a two‐step
sequential approach) [97].
278 16 Diagnosis and Management of Infection in the Diabetic Foot

16.9.2.5 Diagnostic Strategies

As shown in Table 16.3, using a combination of symptoms, physical examination, labora‑
tory tests, and imaging studies, patients can be placed in one of four categories describing
the likelihood of osteomyelitis. Over time, the diagnosis can become more or less likely,
depending on changing clinical and laboratory findings, but this is not taken into account
in the scheme. Of note, the proposed scheme has not yet been validated by any study.

16.9.3 Treatment
16.9.3.1 Overview
Treatment of diabetic foot osteomyelitis is difficult because of the frequent presence of
necrotic bone and biofilm, and perhaps by the limited presence of leukocytes and
insufficient levels of antibiotics [8, 9, 11]. It has been long held that surgery is needed to
remove necrotic and infected bone, but there are now hundreds of published reports of
apparently successful remission of diabetic foot osteomyelitis without surgery. Although
there may be some benefit to early surgical intervention, there is little evidence to help
choose between primarily medical and primarily surgical treatment [8, 9]. Numerous
­surgical interventions have been described, e.g., debridement to bleeding bone marrow
with epidermal sheet grafting, two‐stage debridement with secondary closure and limb
amputation [8]. More recently, ‘conservative’ surgery, i.e., minimizing the resection of
bone, has been shown to be effective in many cases. There are some potential advantages to
surgical therapy, such as a shorter duration of treatment and a reduced likelihood of devel‑
opment of bacterial resistance to antibiotics. Disadvantages, however, are the higher likeli‑
hood of further foot complications after surgery, such as transfer ulcers and amputations
due to changed biomechanical properties of the foot.
In two retrospective studies of diabetic patients with deep foot infections (with and with‑
out osteomyelitis) there was a significant reduction of major amputation with early surgery
combined with antibiotics versus antibiotics alone (27–13% in one study, [98] 8% to 0% in
another [99]). Because of the belief that pus and necrosis need to be debrided, there are no
prospective randomized trials of such cases that include a treatment arm without surgery.
In one RCT assigning diabetic foot osteomyelitis patients who did not require immediate
surgery to conservative treatment with antibiotics versus surgical intervention (with
­antibiotics), outcomes were not significantly different in the two arms [9].

16.9.3.2 Antimicrobial Therapy

Most studies of the use of antibiotics in diabetic foot osteomyelitis lack the long period of fol‑
low up necessary to ensure that remission really means cure, and do not define the duration
of treatment of osteomyelitis. Few studies specified the sensitivity of the causative organisms
or provided information about surgical technique or removal of any surgical hardware. In the
systematic review of the IWGDF [9], among 11 studies on antibiotic treatment of diabetic foot
infection including osteomyelitis the specific antibiotic regimen or route of administration
did not significantly affect the outcome [71]. Furthermore, oral and parenteral therapies
achieve similar cure rates, with oral therapy having the advantage of being less expensive and
avoiding risks associated with intravenous catheters [100]. Oral antibiotic therapy is a reason‑
able choice for osteomyelitis caused by organisms for which there are appropriate oral agents
available. Agents with high oral bioavailability and bone penetrations, such as fluoroquinolo‑
nes and clindamycin, seem to be particularly suitable for treating osteomyelitis [8, 9].
Table 16.3 Scheme for the diagnosis of osteomyelitis [10, 103].

Post-test
probability of Management
Category osteomyelitis advice Criteria Comments

Definite >90% Treat for Bone sample with positive culture AND positive histology OR Sample must be obtained at
(‘beyond osteomyelitis Purulence in bone found at surgery OR surgery or
reasonable Atraumatically detached bone fragment removed from ulcer by through uninvolved skin
doubt’) podiatrist/surgeon OR Definite purulence identified by
Intraosseous abscess found on MRI OR experienced
Any two probable criteria OR surgeon
One probable and two possible criteria OR Definite bone fragment identified by
Any four possible criteria below experienced surgeon/podiatrist
Probable (‘more 51–90% Consider Visible cancellous bone in ulcer OR Sinus tract; sequestrum, heel or
likely than not’); treating, but MRI showing bone oedema with other signs of osteomyelitis OR metatarsal
further Bone sample with positive culture but negative or absent histology OR head involved; cloaca
investigation
may be needed Bone sample with positive histology but negative or absent culture OR
Any two possible criteria below
Possible (but on 10–50% Treatment may Plain X‐rays show cortical destruction OR
balance, be justifiable, MRI shows bone oedema OR cloaca, OR
less rather but further Probe to bone positive OR, Visible cortical bone OR
than more likely) investigation
usually advised ESR >70 mm/h with no other plausible explanation OR
Non‐healing wound despite adequate offloading and perfusion for
>6 weeks OR ulcer of >2 weeks duration with clinical evidence of infection
Unlikely <10% Usually no need No signs or symptoms of inflammation AND normal X‐rays AND ulcer
for further present for <2 weeks or absent AND any ulcer present is superficial OR
investigation or Normal MRI OR
treatment Normal bone scan
280 16 Diagnosis and Management of Infection in the Diabetic Foot

16.9.3.3 Adjunctive Therapy for Osteomyelitis

There are no published studies of reasonable quality that suggest that the use of larvae,
antibiotic‐loaded polymethacrylate beads or vacuum assisted closure are helpful in treating
diabetic foot osteomyelitis [9, 101].

16.9.3.4 Duration of Treatment

The optimal duration of antimicrobial therapy in diabetic foot osteomyelitis is not entirely
clear [8, 9, 11]. In most studies patients were treated for six weeks, but in some patients
received antibiotics for six months (or longer). The mean duration of antibiotic treatment
found in the studies included in the IWGDF systematic review was short, ranging from 6 to
28 days [9]. The optimal duration of treatment with antibiotics depends upon the amount
of debridement or resection provided. Treatment of a few days to a couple of weeks is
­usually sufficient after aggressive surgical debridement removes all infected bone [8, 11].
One study in patients with limited osteomyelitis of the forefoot, treated conservatively,
found no difference in outcome between patients treated for 6 versus 12 weeks [102].
Several months of antibiotic therapy may be needed in patients with necrotic and infected
bone who undergo limited or no debridement [8, 9, 11].

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 287

17

Surgical Approach to Diabetic Foot Infections

Katherine M. Raspovic1, Javier La Fontaine1, and Lawrence Lavery2
1
Department of Orthopaedic Surgery and Department of Plastic Surgery, UT Southwestern Medical Center, Dallas, TX, USA
2
Department of Plastic Surgery, Orthopaedic Surgery, and Physical Medicine & Rehabilitation, UT Southwestern Medical
Center, Dallas, TX, USA

17.1 ­Introduction

Diabetic foot infection (DFI) is a serious complication of diabetes mellitus (DM) and if
not treated properly and aggressively, can be limb and life threatening. Early recogni-
tion and prompt intervention are the keys to initial treatment of DFI. A delay in care
may lead to further spread of infection locally and systemically. Aggressive and timely
treatment is of the utmost importance. A DFI typically begins at a portal of entry such
as ulceration or puncture wound in patients with peripheral neuropathy. This entry
point allows pathogens to invade deeper tissues. Ulcers that probe to bone, ulcers open
for greater than 30 days, and presence of peripheral vascular disease have been shown to
be independent risk factors associated with DFI development [1]. A longitudinal study
of 1666 patients with DM revealed that once an infection develops, the risk of hospitali-
zation was 55.7 times greater and the risk of amputation was 154.5 times greater com-
pared to patients with DM but without infection [1]. In addition to DM and peripheral
neuropathy, DFI often presents with concomitant peripheral arterial disease, end stage
renal disease, and lower extremity soft tissue or osseous deformity, making the treat-
ment and healing process more challenging. Patients with DFI face tremendous physi-
cal and mental burden. A study of patients hospitalized with DFIs revealed significantly
reduced physical and mental quality of life [2]. In this study, a group of 47 patients
hospitalized for DFI were compared to a group of 47 patients with DM, but no DM
related foot complaints. The groups were matched for age and gender. The DFI cohort
consisted of 15 patients with moderate and 32 patients with severe DFI, according to the
Infectious Disease Society of America guidelines [3]. All patients in both groups com-
pleted both the Medical Outcomes Study Short Form 36-item health surgery (SF-36) and
the Foot and Ankle Ability Measurement (FAAM). Patients in the DFI group had
­significantly reduced scores in all eight subscales of the SF-36 and the FAAM activity of

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
288 17 Surgical Approach to Diabetic Foot Infections

daily living and sports scores when compared to DM patients without DFI [2]. This
study clearly demonstrates the significant physical and mental challenges that patients
with DFI face. Patients with DFI are also at greater risk for amputation. A recent study
of 119 patients hospitalized due to DFI showed that 50% of these patients underwent
amputation at some level, with 16% requiring a below knee amputation [4]. Patients
with diabetes foot-related complications have even been shown to fear major lower
extremity amputation more than death [5].

17.2 ­Initial Evaluation

The initial examination of a DFI can occur in the outpatient setting, emergency depart-
ment, or inpatient setting. When evaluating a patient with suspected DFI, one must
perform a detailed history and physical examination in order to determine the most
appropriate intervention. Important factors to note in the patient history are recent
injury to the foot (such as a puncture wound), presence of ulceration, ulcer duration,
history of recurrent ulcer or amputation, family history of DM or amputation, tobacco
use, diabetes duration, previous foot infection, overall diabetes management ­compliance,
and recent glycemic control. An increase from a patient’s ‘baseline’ in blood glucose
levels is often an early signal of developing DFI. Loss of appetite, feeling lethargic, or
‘flu –like’ symptoms are signs of worsening or severe DFI. Vital signs must be evaluated
for signs of sepsis such as hypotension, tachycardia, and tachypnea. Physical examina-
tion must include a detailed dermatological, vascular, neurological, and musculoskele-
tal examination of both lower extremities. Dermatological examination must include
identification of the portal of entry of the infection. The ulceration depth must be
examined to determine the extent of tissue involved by the ‘probe to bone’ test. The area
must be evaluated for presence and extent of erythema, edema, malodor, colour of
drainage, presence of purulence, increase in temperature, crepitus of surrounding tis-
sues, and tissue darkening/ischemic changes. Vascular examination should include pal-
pation of pedal pulses and if they are not palpable, a bedside Doppler should be utilized
to help identify audible arterial flow signals. Non-invasive arterial studies (ankle bra-
chial index [ABI], toe brachial index [TBI], and absolute great toe pressures) should be
obtained to further evaluate for underlying peripheral arterial disease if clinically indi-
cated, however, these are often performed after initial surgical intervention to address
the infection. Obtaining non-invasive arterial studies should not delay or interfere in
taking a patient to the operating room, as immediate infection control takes precedent
over ischemia initially. Neurological examination should be used to determine the pres-
ence and or the extent of peripheral neuropathy and may include light touch evaluation
with a 5.07 Semmes Weinstein monofilament, vibratory sensation with a 128 Hz tuning
fork, and evaluation of Achilles tendon reflexes. The vast majority of patients with DFI
have some degree of neuropathy, and this may impact postoperative offloading.
Musculoskeletal examination should include evaluation of the presence of osseous
deformities such as Charcot neuroarthropathy, prominent osseous structures, tendon
contractures, muscle strength/imbalances, hallux valgus, hammertoe contractures,
and overall alignment of the foot, hindfoot, and ankle. Previous amputation level
 17.2 ­Initial Evaluatio 289

(if ­present), presence of equinus due to Achilles tendon or gastroc-soleus contracture,

as well as joint range of motion should be noted. These types of deformities may have
to be addressed after stabilization of the infection in order to achieve soft tissue healing
and prevent recurrence.
Radiographic evaluation is appropriate in acute DFI to evaluate for signs of osteomy-
elitis, soft tissue emphysema or ‘gas’ and/or foreign bodies. ‘Gas’ extending through the
soft tissues on radiographic evaluation is concerning for a severe and more rapidly
spreading infection which warrants emergent surgical intervention. Advanced imaging
modalities such as computerized tomography (CT) or magnetic resonance imaging
(MRI) can better identify soft tissue emphysema, abscess, or osteomyelitis. In patients
with severe infections, delaying surgical intervention should not be done to obtain
advanced imaging. Laboratory values such as erythrocyte sedimentation rate (ESR),
C-reactive protein (CRP), complete blood count with differential (CBC), haemoglobin
A1c (HbA1C), serum glucose, albumin, pre-albumin, comprehensive metabolic panel,
lactate, anion gap, and presence of acidosis, must also be evaluated. Prothrombin time
(PT), partial thromboplastin time (PTT), and international normalized ratio (INR)
should be evaluated and addressed as needed, as many patients with DFI are anticoagu-
lated. It is important to keep in mind during the examination that patients with DFI may
not manifest leukocytosis or other systemic signs of infection, and may not experience
pain [6].
The DFI severity level can help guide proper treatment. In 2012, the IDSA updated
their DFI guidelines and further distinguished moderate from severe infections by incor-
porating systemic inflammatory response syndrome (SIRS) [3]. DFI classification will be
further discussed in a different chapter. Of note, a recent study of 119 patients hospital-
ized with DFI demonstrated that SIRS is valid in distinguishing between moderate and
severe DFI [4]. Patients in this study with severe DFI had a 2.55-fold increased risk for
any level of amputation and a 7.12-fold increased risk of major amputation compared to
patients with a moderate DFI [4]. The University of Texas Classification is another
important and commonly used classification system. This system includes wound stag-
ing and also risk stratification by including the presence or absence of infection and
ischemia [7].
In general, mild infections can be treated in the outpatient setting with oral antibiotic
therapy, wound care, and offloading. However, most moderate and all severe DFI require
hospitalization, employing empiric intravenous antibiotic therapy, and surgical interven-
tion when indicated. When a comprehensive and systematic examination and imaging
findings are concerning for underlying abscess, osteomyelitis, or ‘gas’ in the soft tissues,
prompt surgical intervention is required. Although rare, necrotizing soft tissue infections
are characterized by their rapid spread and associated systemic illness [8]. Early recogni-
tion is key and there must be a high index of suspicion in patients with skin changes such
as erythema, bullae, skin necrosis, in the setting of organ system failure [8]. The Laboratory
Risk Indicator for Necrotizing Fasciitis (LRINEC score) was developed by Wong et al. [9].
This scoring system utilizes laboratory values to help better identify necrotizing soft tissue
infections [9]. Scoring systems may aid in diagnosis, however a high index of suspicion
and prompt intervention is paramount. Early recognition and intervention is key to pre-
serving loss of limb and life.
290 17 Surgical Approach to Diabetic Foot Infections

17.3 ­Initial Surgical Intervention

The goal of initial surgical intervention is to control and eradicate the DFI by draining an
abscess and to sharply remove infected and non-viable soft tissue and bone. La Fontaine
et al. [6] described a systematic stepwise approach as ‘incision, inspection, debridement,
culture, irrigation, hemostasis, and post-operative care’ [6]. Incision, drainage, and debride-
ment are initially performed with the goal of preserving a functional limb. In some cases,
infection is so severe that, an amputation of some level (i.e. toe, transmetatarsal, Chopart
level) is required at the initial surgical intervention to manage soft tissue and/or osseous
involvement and destruction. Surgical incisions should be extensile, encompassing the
area of ulceration/portal of entry and abscess. Surgeons should plan the incision with the
ultimate thought of closure.
Understanding the anatomical components of the compartments of the foot is key for
surgical eradication of a DFI. Prompt drainage of involved compartments is critical, as
abscess decompression reduces compartment pressures and prevent further tissue necro-
sis. Nearly 90 years ago, Dr. Manuel Grodinsky’s work [10] was the first to describe plantar
compartments of the foot (medial, central, and lateral). He also reported on the ‘routes of
spread’ of infection, originating from the level of the toes, coursing plantarly and proxi-
mally [10]. Grodinsky described a medial incision for approach to the plantar foot, in order
to avoid a plantar scar [10]. In 1980, Loeffler and Ballad [11] defined five plantar fascial
spaces and proposed a plantar incision to adequately visualize all plantar spaces in the set-
ting of infection [11]. They recommended an extensile incision starting posterior to the
medial malleolus that extended plantarly towards the arch, coursing towards the first and
second metatarsal heads [11]. This incision allows for thorough evaluation and drainage of
plantar foot infections and based on Loeffler and Ballard’s clinical experiences, plantar
scarring was not an issue [11]. Another benefit of this incision is that it could be extended
proximally to decompress abscesses in the leg.
There is debate regarding the number of compartments of the foot. Manoli’s study of
compartment syndrome of the foot due to trauma identified nine compartments [12].
These nine compartments are described as the medial, lateral, central (superficial and deep
portions), calcaneal, four interossous compartments, and the adductor compartment [12].
Manoli’s study did not specifically evaluate the dorsum of the foot but it has been sug-
gested that this is also an additional compartment since the extensor digitorum brevis mus-
cle is present here [13]. Although Manoli’s work on describing the compartments of the
foot was trauma focused, understanding the anatomy and fascial spaces of the foot is criti-
cal in treating DFI. Increased compartment pressure due to DFI will lead to tissue necrosis
[6]. Edema due to infection can lead to thrombosis and occlusion of arterial flow to the
distal arteries, as well as outflow venous obstruction [6]. Therefore, understanding the con-
tents of the various foot compartments is of utmost importance to successful surgical eradi-
cation of DFI. (Figures 17.1 and 17.2).
DFI often spreads along the course of tendons due to the fact that these are the path of
least resistance [6]. In general, incisions will follow these paths as well [6]. Regarding inci-
sion placement for plantar DFI, Fisher et al. [14] suggested a modification to the Loeffler-
Ballard incision. They recommend starting distally at the affected interspace and extending
the incision proximally through the medial arch and towards the medial malleolar region
 17.3 ­Initial Surgical Interventio 291

Figure 17.1 This drawing illustrates the medial, central, and

lateral compartments of the plantar foot.

1 2 3

Figure 17.2 This drawing illustrates a

cross sectional view through the mid-foot.
4

1 2 3

as necessary [14]. We also agree with the approach by Fisher et al. [14] and utilize this as
our standard surgical approach for plantar DFI.
Ideally, surgical incisions should be made over areas of maximal arterial flow in order
to ensure the best chance of soft tissue flap survival [15]. Regarding foot amputations,
ideally medial and lateral incisions should be made at the glabrous juncture, where the
dorsal and plantar tissue meet because this is where the dorsal and plantar angiosomes
meet [15]. If arterial circulation is compromised, it is critical to ensure that there is suf-
ficient flow to the flap that will be used for closure [15] and this will be discussed further
in another chapter. There are six angiosomes of the foot and ankle [16] that originate
from the anterior tibial, posterior tibial, and peroneal arteries [16]. The posterior tibial
292 17 Surgical Approach to Diabetic Foot Infections

artery supplies the medial calcaneal branch (heel), the medial plantar artery (instep), and
the lateral plantar artery (lateral midfoot and forefoot) [16]. The two branches of the
peroneal artery are the anterior perforating branch which supplies the lateral anterior
upper ankle, and the calcaneal branch which feeds the lateral plantar heel [16]. The ante-
rior tibial artery supplies the anterior ankle and when it branches into the dorsalis pedis
artery, it supplies the dorsal foot [16]. Knowledge of these angiosomes permits proper
placement of incisions.
The involved surgical area should be closely inspected for tunnelling, dorsal or plantar
and proximal or distal tracking. Any involved muscular or tendinous structures must be
closely examined for infection tracking along tendon sheaths. The infection must be fol-
lowed proximally and distally until normal tissue is identified. Any non-viable soft tissue,
muscle, tendon, or bone must be removed. Non-viable tissue can be removed utilizing scal-
pels, hydroscalpel (Versa-jet), curettes, or rongeurs. A sagittal saw, osteotomes, and ron-
geurs can be used to remove or cut bone [17]. Dr. Christopher Attinger’s principle of using
colour is a practical and simple method to guide the adequacy of surgical debridement [17].
Non-viable tissue colour is abnormal and may be grey, brown, green, purple, or even black
in appearance [17]. This tissue must be removed. Healthy tissue will demonstrate red,
white, and yellow coloration; normal fat is yellow, muscle, and granulation tissue should be
red. Tendon and fascia should be white and bone should be white or pale yellow [17]
(Figures 17.3 and 17.4).

Figure 17.3 This pre-operative radiograph of a patient

with severe DFI demonstrates ‘gas’ in the lateral soft
tissue spreading proximally.
 17.4 ­After Initial Surgical Interventio 293

Figure 17.4 This is a post-operative photo of the patient in Figure 17.3. This patient underwent
extensive incision and drainage. The photo demonstrates extension of the incision proximally up
the leg due to the extension of the DFI along the course of the peroneal tendons.

During the surgical intervention, obtaining deep tissue cultures will help guide antibiotic
therapy. If the infection extends to the level of bone, a bone sample should be obtained for
culture and/or pathological analysis. Intra-operatively, pre-debridement cultures should be
taken of the non-viable tissues before irrigation/debridement. Once all infected and non-
viable soft tissue and bone is removed, the area should be thoroughly irrigated. Different
techniques and devices for irrigation exist, each with their own advantages and disadvan-
tages. After the area is irrigated, the surgical site should be closely inspected for any signs
of remaining infection. At this point, post debridement cultures should be obtained. It is
not unusual to experience significantly bleeding after debridement and meticulous
­haemostasis is mandatory, especially in patients with open wounds. Haemostasis can be
achieved with compression, electrocautery, and topical agents if needed (topical thrombin,
gel foam, etc.). The choice of dressing is dependent on the surgical site environment; if the
surgical area requires close monitoring, a simple dressing such as a ‘wet to dry’ is preferred.
Wounds with significant drainage can be packed open, or alternatively, negative pressure
therapy (with or without instillation) can be applied to the surgical area that has good arte-
rial ­perfusion [18, 19].

17.4 ­After Initial Surgical Intervention

After initial surgical intervention has been performed and all grossly infected and non-
viable tissue has been debrided, several important steps must be taken during the time
prior to subsequent return to the operating room.
Vascular Surgery Consultation: A detailed clinical vascular examination, including non-
invasive arterial studies if indicated, should be performed. Initially, the surgical manage-
ment of the infection takes precedence over vascular assessment and obtaining these
studies may be delayed until after the initial surgical intervention. The prevalence of PAD
294 17 Surgical Approach to Diabetic Foot Infections

in patients with DM and ulceration has been shown to be nearly 50% [20]. A recent study
of 207 patients with DM identified PAD in approximately 50% of patients; 80 of these
patients had DM related foot pathology and 23 patients had DM but foot pathology not
related to their DM [21]. Non-invasive arterial studies should include evaluation of ABI,
TBI, and absolute great toe pressures if possible. The ankle brachial index may be falsely
elevated in the setting of medial artery calcinosis (MAC), therefore measurement of the
TBI is more accurate as these vessels are much smaller and are less susceptible to MAC
[22–24]. Prompt consultation with a vascular expert should be obtained when there are
abnormal clinical exam findings and/or abnormal non-invasive arterial exam results.
Depending on the available medical expertise this may include vascular surgeons, inter-
ventional radiologists or cardiologists.
Infectious Disease Consultation: Patients with DFI are generally started on broad-spec-
trum intravenous antibiotics due to the polymicrobial nature of DFI. Empiric antibiotic
therapy is then tailored based on intra-operative culture results. If available, we recom-
mend consultation of an Infectious Disease Specialist for guidance and management of
antibiotic therapy. The timing and duration of antibiotic therapy is debatable and will be
discussed in a different chapter in this text.
Plastic Surgery Consultation: Soft tissue defects after surgical eradication of infection
may require sophisticated closure techniques such as local flaps, rotational flaps, or even
microsurgical free tissue transfer for coverage of larger defects. Consultation of a plastic
surgeon may be necessary in certain clinical scenarios for their expertise in soft tissue cov-
erage. In some cases, soft tissue coverage by a plastic surgeon may prevent the need for
more proximal level amputation [25]. There are various options for coverage of soft tissue
defects of the foot and ankle depending on the size and location of the wound, however
success of any flap is dependent on factors such as host comorbidities and adequate arterial
supply [25, 26]. The majority of wound closure after DFI eradication can be achieved with
more simple techniques however about 10% cases will require a flap reconstruction [27]
due to extensive tissue loss. We advise early plastic surgery consultation for coverage plan-
ning, especially if this can prevent a more proximal amputation.
Other Key Consultations: Other key consultations in the inpatient setting may include
internal medicine, endocrinology, nutrition/dietician, physical, and occupational therapy,
as well as social work. In the outpatient setting, consultation with an orthotist and or pros-
thetist may be beneficial once the patient is healed and ready for ambulation.

17.5 ­Staged Surgical Intervention and Wound Closure

Serial surgical debridements may be necessary to completely eradicate the infection.

Timing of wound closure is typically determined by the culture results from the most
recent surgical intervention in conjunction with the clinical appearance of the tissue. Once
it is determined that the wound is clean based on intra-operative culture results and the
clinical appearance, it is time to move forward with closure and or reconstruction of the
soft tissue defect. A recent study by Elmarsafi et al. [28] evaluated surgical site dehiscence
rates and semiquantitative culture results at the time of wound closure [28]. This study
included 65 patients with comorbidities such as DM, renal disease, coronary artery disease,
 17.5 ­Staged Surgical Intervention and Wound Closur 295

history of stroke, PAD, and history of tobacco use. The majority of patients had DM (70.8%)
and lower extremity wounds (90.7%). Closures performed included split thickness skin
grafting (STSG), delayed primary closure, advanced biologic application, local flaps, and
free tissue transfer. This study revealed four significant findings: (i) the number of surgical
interventions/debridements did not influence the wound dehiscence rates after closure,
(ii) cultures obtained at closure which grew coagulase negative staphylococcus were a sig-
nificant risk factor for wound dehiscence, (iii) post debridement cultures with scant or rare
growth in enrichment broth at closure did not affect the overall dehiscence rates, (iv) the
species number and semi -quantitative culture results improved with each surgical
­debridement [28].
There are multiple wound closure techniques, depending on the extent of the soft tissue
defect, including delayed primary closure, autogenous skin grafting, bioengineered tissues,
local flaps, pedicled flap, or free tissue transfer [27]. After surgical eradication of DFI, the
majority of wounds can be closed with modalities such as delayed primary closure, biologic
products/advanced skin substitutes, or negative pressure wound therapy (NPWT).
Examples of biologic products/advanced skin substitutes are human amniotic membrane,
living skin equivalents, and bovine collagen matrix products. A recent multi centre, rand-
omized clinical study compared the efficacy of the treatment of diabetic foot ulceration
using cryopreserved placental membrane compared with standard of care [29]. They found
that patients treated with the cryopreserved placental had a shorter time to healing, less
adverse events, and fewer wound related infections compared to the patients treated with
standard of care alone [29]. Iorio et al. [30] reviewed a series of 105 patients who under-
went application of a collagen bilayer matrix for closure of 121 lower extremity wounds.
Eighty per cent of patients in this study had DM. The overall salvage rate for all patients
was 77%. NPWT is a key adjunctive treatment that has been used for many different wound
types and locations. It can be used to facilitate granulation tissue formation, or can main-
tain a clean wound environment in between visits to the operating room. A recent review
by Anghel et al. [18] identified 1347 publications on NPWT [18]. They further identified
only randomized controlled trials that included 30 or greater subjects. A total of 23 publica-
tions met their criteria. Seven studies evaluated wounds in patients with diabetes foot
related issues due to surgery or ulceration. Their review of the diabetic foot NPWT studies
revealed that overall, NPWT is a safe and useful tool in this patient population [18]. The
development of NPWT with instillation allows for periodic irrigation of an infected or con-
taminated wound, in conjunction with standard NPWT. There is debate regarding which
solution is most effective. A prospective, randomized, study by Kim et al. [31] evaluated
NPWT with instillation and compared 0.9% normal saline versus 0.1% polyhexanide plus
0.1% betaine in a group of hospitalized patients undergoing surgical treatment of infected
wounds [31]. One hundred patients were included in the study. Overall, there was no sta-
tistically significant difference between the two solutions used for instillation in regards to
number of operating room visits, their length of hospital admission, the number of wounds
that were closed, and the number of wounds that remained closed at the 30 day follow up.
Overall, their findings suggest that the actual instillation process rather than the type of
solution used is key to success with this modality [31]. Once a wound bed has achieved suf-
ficient granulation tissue formation via NPWT or application of biologics, STSG may be
used in the final step for closure. A recent study at University of Texas Southwestern
296 17 Surgical Approach to Diabetic Foot Infections

Medical Center evaluated patients with diabetes who underwent STSG application for cov-
erage of foot and ankle wounds [32]. Forty-one patients and 43 surgical sites were evalu-
ated and the authors reported that 27 sites healed or had greater than 90% of STSG
incorporation. When comparing patients who healed to patients with graft failure, there
was no significant different in HbA1c levels (P = 0.72). The findings suggest that the ben-
efit of earlier wound closure outweighs the risk of STSG surgical intervention in patients
with elevated HbA1C levels [33]. In the setting of a large soft tissue defect, free tissue trans-
fer may be required in an effort to prevent more proximal level amputation. This will be
discussed in detail in another chapter.

17.6 ­Surgical Offloading

Once wound closure, soft tissue reconstruction, or the definitive soft tissue procedure has
been performed, offloading is critical for complete healing to occur. The heel is especially
challenging to treat due to constant and direct pressure on this area. Application of an
external fixation device can provide complete offloading until a wound is healed. Dalla
Paola et al. [34] prospectively studied a group of patients with DM who underwent surgical
intervention due to osteomyelitis caused by chronic heel ulcerations. All patients under-
went subtotal calcanectomy with application of a circular external fixator to offload this
area. Eighteen patients were included and the average follow up time was 212.3 days. All
patients healed with an average time to healing of 69 days [34]. There are various constructs
for offloading frames to include circular and traditional external fixation [35]. The design
configuration must be based on the location of the wound. Application of an external fixa-
tor for offloading requires knowledge of the principles of external fixation as well as man-
agement of potential associated complications [35]. Application of external fixation in
patients with diabetes is not without complications. A study by Wukich et al. [36] of
patients with undergoing circular ring fixation revealed that patients with DM had a seven-
fold risk for pin site complications compared to patients without DM [36]. Their findings
reinforce the fact that close follow up and pin site monitoring is critical in this patient
population [36].

17.7 ­Soft Tissue/Tendon Balancing and Definitive Osseous

Surgical Reconstruction

Once the DFI has been eradicated, and/or the wound has healed, prevention of re-ulceration
reinfection is critical. During the initial evaluation of a DFI, one must determine if biome-
chanical abnormalities contributed to the initial ulceration and subsequent infection.
Increased plantar pressure and shear may result from tendon contracture, tendon imbalance
and osseous deformity. In the setting of neuropathy and peripheral arterial disease, a non-
plantigrade foot will lead to re-ulceration. For example, resection of the base of the fifth meta-
tarsal will cause an equinovarus deformity due to overpowering of the posterior tibial tendon
and absence of its antagonist, the peroneus brevis. One must critically assess all lower
­extremity soft tissue and osseous structures before and during the course of DFI ­treatment in
 17.8 ­Decision for Proximal Level Amputatio 297

order to determine the appropriate surgical timing in which these factors may be addressed
and corrected if needed. This may occur during the same timeline of treatment of a DFI once
the DFI has been eradicated or may be performed at a different setting or time.
Soft Tissue/Tendon Balancing: Soft tissue and tendon balancing is key to address deformi-
ties that occur in the setting of foot amputations that occur due to DFI. Contracture of the
Achilles tendon is one of the most common findings in patients with diabetes foot related
complications, resulting in decreased ankle dorsiflexion and increased plantar forefoot pres-
sure. It has been demonstrated that structural abnormalities of the tendon occur in patient
with diabetes [37]. Increased forefoot pressure can lead to callus formation, ulceration, and
subsequent DFI. A Silfverskiold test should be performed on each patient to assess for
Achilles or gastrocnemius contracture. This test examines the amount of ankle dorsiflexion
present with the knee extended and then flexed. In a gastrocnemius contracture, when the
knee is flexed, there will be additional dorsiflexion of the ankle joint. In the presence of an
Achilles contracture (gastrocnemius and soleus), there is equinus when the knee is extended
and this does not improve with knee flexion [38]. Based on the clinical findings previous
mentioned, an Achilles tendon lengthening or gastrocnemius recession may be performed as
needed. These procedures increase the amount of ankle dorsiflexion and therefore decrease
the amount of pressure on the forefoot. Achilles tendon lengthening can be performed per-
cutaneously (Hoke triple hemisection), or through an open incision. A study by Laborde
et al. evaluated 28 feet in 24 patients who underwent a gastrocnemius recession for midfoot
Charcot neuroarthropathy with and without plantar ulceration. Treatment was considered a
success if the patient was ambulatory without an ulcer or an amputation at the time of final
follow up. Overall, 88% of patients were successfully treated by this method at an average of
37 months post operatively [39]. The tibialis anterior is also a deforming force that must be
closely evaluated. Most recently, the concept of tibialis anterior tendon lengthening has been
introduced by Kim et al. [40]. They believe that the contracted tibialis anterior increases
varus force on the lateral column of the forefoot, leading to ulceration. Tendon transfers such
as the split tibialis anterior tendon transfer or posterior tibial tendon transfer may also be
used, depending on the location of ulceration and presence of a flexible deformity. In the
setting of DFI treatment and contracture, these procedures should only be performed when
the DFI has been completely eradicated and treated appropriately.
Osseous Deformity: If necessary, osseous deformity must also be corrected in order to
prevent recurrence of ulceration and ultimately DFI. Charcot neuroarthropathy commonly
leads to ulceration and subsequent DFI. Reconstruction of deformity due to Charcot will be
discussed in a different chapter of this text.

17.8 ­Decision for Proximal Level Amputation

DFI may cause severe tissue and osseous destruction that may necessitate a proximal level
amputation. In the acute setting, a staged or ‘guillotine’ amputation may be necessary to
control infection. Once the patient is stabilized and the wound appears healthy, definitive
amputation and closure can be completed. In some cases, patients with a non-functional
foot, insensate foot, and chronic infection may benefit from transtibial amputation. Wukich
et al. [41] evaluated 81 patients who underwent below knee amputation due to DM related
298 17 Surgical Approach to Diabetic Foot Infections

foot complications. Patients were evaluated at a minimum of one year post operatively. In
general, the findings demonstrated that in select patients, transtibial amputation resulted
in significant improvement in quality of life and function [41].

17.9 ­Conclusions

DFI is a serious complication of DM and if not treated properly and aggressively, can be limb
and even life threatening. Early recognition and prompt intervention are the keys to success-
ful treatment. Initial evaluation including a detailed physical examination, evaluation of
laboratory values, and imaging will guide the incision decision for treatment. Most ­moderate
and severe DFI will require hospitalization, intravenous antibiotic therapy, and surgical
intervention. Surgeons treating DFI must utilize a systematic approach. Patients must
return to the operating room for subsequent surgical interventions as many times as neces-
sary in order to completely eradicate the DFI. Surgical cultures will help guide antibiotic
treatment and soft tissue closure or reconstruction. Soft tissue/tendon balancing and correc-
tion of osseous deformity of the lower extremity may be required once DFI is eradicated in
order to prevent re-ulceration and re-infection. Due to the multifaceted nature of DFI, a
team approach is critical for successful treatment and prevention of recurrence.

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 301

18

The Evidence Base for the Choice of Dressings

in the Management of Diabetic Foot Ulcers
William J. Jeffcoate1, Patricia E. Price2, and Frances L. Game3
1
Nottingham University Hospitals NHS Trust, Nottingham, UK
2
Cardiff University, Cardiff, UK
3
University Hospitals of Derby and Burton NHS Foundation Trust, Derby, UK

18.1 ­The Problems

18.1.1 Failure of DFUs to Heal Promptly

Data from the National Diabetes Foot Care Audit of England and Wales indicate that
only about half of all 22 653 diabetic foot ulcers (DFUs) registered between 2014 and
2017 healed by 12 weeks, while the proportion healed by 24 weeks was only two‐thirds
[1]. Data from other sources suggest that the time to healing may sometimes be very
much longer and one recent report of management primarily in the community in the
UK reported that the percentage healed within 12 months was only 35% [2]. Whatever
the correct figure for DFUs of different type and severity, it is clear that the time
to healing of DFUs is often very delayed and healing does not happen at all in a
sizeable percentage. This delayed and uncertain outcome inevitably causes considerable
suffering and cost.

18.1.2 Cost
There are estimated to be some 60 000 active DFUs in UK at any one time although
some estimates are very much higher [3]. Each ulcer will have its dressing changed
on average two to three times each week. Each dressing change involves removal of the
old preparation, inspection, cleaning and treatment of the wound surface and dressing
replacement. The total cost of managing foot ulcers in England is now estimated to be of
the order of £900 million and 60% of this cost is incurred in the community [4]. The cost
of diabetic foot ulcers amounts to just less than 1% of the total NHS budget.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
302 18 The Evidence Base for the Choice of Dressings in the Management of Diabetic Foot Ulcers

18.1.3 Need for Evidence

In the circumstances, it is almost unbelievable that the deployment of this vastly expensive
aspect of clinical care is conducted with only minimal consideration of either evidence
(evidence to underpin dressing choice) or comparative assessment of performance between
providers. The study reporting community care in UK, for example, reported that 48%
received treatment with compression bandaging even though none had a history of either
venous disease or of lymphoedema and despite the lack of any evidence to support its use
for DFUs [2]. Indeed, the use of compression bandaging in this report was associated with
a worse outcome and increased cost.
Current regulations require that wound dressings (classified as devices) need only to
have evidence of safety, rather than efficacy or cost effectiveness prior to marketing.
Clinicians and patients are likely to be susceptible to claimed clinical benefits of marketed
products if they become frustrated by any seeming lack of progress with current treat-
ments. As seeming lack of progress is commonplace, it should be a responsibility for all
professionals involved in wound care to ensure that they choose only the most effective
products and that in the absence of robust evidence of effectiveness, they should choose
only the cheapest and most acceptable ones. This is a responsibility for which many nurses
and nearly all doctors have little or no training.

18.2 ­Quality of Evidence

Assessment of the quality of experimental evidence is based on studies which show that
the use of a treatment is associated with an outcome which is better than controls. Studies
which are uncontrolled and simply show an improvement with time, such as case reports
and case series, are of limited scientific value because nearly all DFUs will improve with
time (and the majority will eventually heal in most series). Randomised controlled trials
(RCTs) provide the most robust evidence of effect although assessment of the quality of an
RCT requires care because of the overall number of criteria which need to be satisfied [5].
These criteria need to be satisfied in order to minimize the possibility of bias – with ‘bias’
meaning any factor other than the treatment being studied which could have contributed
to the outcome of the study. The results of RCTs are conventionally collated by systematic
reviews but systematic reviews have to be conducted with care and, ideally, by experts in
the field because of the difficulty which might be encountered in assessing some of the
outcomes being compared [6]. The conclusions of this review are largely based on repeated
systematic reviews undertaken on behalf of the International Working Group of the
Diabetic Foot [7–9], and independently updated using the same search strings, to end
October 2017 (Jeffcoate et al., unpublished data). The evidence cited relates only to DFUs.

18.3 ­The Definition of a Dressing

For the purposes of this review, the term ‘dressing’ will apply to the products and procedures
which are generally used by health care professionals without specialist surgical training or
skills – whether they are nurses, podiatrists, or doctors. These dressings are those which
 18.4 ­The Roles of the Dressin 303

are usually applied or changed in a clinic, hospital ward, or in the patient’s own home and
will be referred to here as ‘routine wound care’. Dressings or products which need to be
administered, applied, or replaced, in a specialised clinical environment (including an
operating theatre) will not therefore be considered in any detail.
The term ‘dressing’ will also be restricted primarily to coverings applied directly to the
surface of the wound in order to promote wound healing. In some cases, this primary
dressing may have active agents incorporated within it. In other cases the primary dressing
will be used in conjunction with active agents which may be applied separately to the
­surface of the wound during routine dressing change and this approach will also be consid-
ered in this review unless the other active agents require either the special skills or facilities
referred to above.

18.4 ­The Roles of the Dressing

All dressings are designed to ensure firstly that the wound surface remains warm and
moist (but not so wet that it becomes macerated) and secondly that the healing tissues
are protected as far as possible from trauma and infection. Secondary dressings and off‐
loading devices contribute to these functions but will not be considered in this review.
Some dressings are designed to be only semi‐permeable and to allow less evaporation of
wound fluid. This can facilitate less frequent dressing changes. On the other hand, their
use can be complicated by excessive fluid accumulation and maceration of the healing
wound. Rather than run this risk it may be better to change dressings rather more often
so that the condition of the wound surface can be checked.
Most dressings are also marketed on the basis that they have ingredients or properties
that may stimulate a wound to heal more quickly. In order to consider these possible actions
(and the evidence that applies) it is useful to consider the broad reasons why healing may
be delayed in the first place (Table 18.1).

Table 18.1 Some reasons why healing of a diabetic foot ulcer may be delayed.

1) Perpetuation of the factors that led to initial ulcer onset:

e.g. trauma, PAD, neglect (neuropathy)
2) Complications: e.g. infection
3) Failures in the healing process related to diabetes:
hyperglycaemia – effect on macrophages and other cells
abnormal pattern of inflammatory response
less well recognised effects of neuropathy on cells involved in the coordination of healing
4) Biology of the chronic wound:
impact of exposure on cell function: e.g. changes in wound microbiome, biofilms,
wound biochemistry – e.g. excessive activity of matrix metalloproteinases (MMPs)
5) Any unwanted effect of other treatments
304 18 The Evidence Base for the Choice of Dressings in the Management of Diabetic Foot Ulcers

18.5 ­Basic Aspects of Wound Care

Any mammal in the wild will, when injured and if it retains the capacity, adopt the simple
wound care measures which form the basis of routine care exercised by humans (whether
professional or not) for either themselves or others who they are looking after. Hence
­routine wound care includes cleaning the wound, protecting it from trauma and regular
review of progress. To these must be added the use of antibiotics for clinically overt infec-
tion. The lack of formal scientific evidence for these basic aspects of care is irrelevant
because it would impossible to undertake a study in which they were not included.

18.6 ­Evidence for Potential Contributions of Dressings and Wound

Applications to Improve Wound Healing

Potential broad mechanisms by which dressings and topical treatments could enhance
healing are listed see Table 18.2. From this list of categories of intervention, the only ones
to be considered here are those which could be adopted in routine wound care.

18.6.1 Debridement
It is believed that a wound that is contaminated by surface debris will not heal as well as
one which is clean.

18.6.1.1 Sharp Debridement

It is similarly generally accepted that attempts to clean the surface of the wound with a
scalpel (‘sharp debridement’) are preferable to other approaches – possibly because one
effect of sharp debridement (especially when it is more thorough) will be to replace existing

Table 18.2 Potential actions by which treatments may enhance healing of diabetic foot ulcers.

1) Debridement and maintenance of a clean wound surface:

a) sharp, autolytic, larvae, hydro‐, topical collagenases
b) antiseptics, honey
2) Effect of other components of dressing products:
a) alginates, carboxymethylcelluose
3) Acellular wound care products and skin grafts and skin substitutes
4) Topical gases
a) Hyperbaric oxygen, topical oxygen/ozone
5) Other therapies which may stimulate healing of chronic wounds
a) Negative pressure wound therapy (NPWT)
b) stem cells, platelets, growth factors
c) products active against matrix metalloproteinases (MMPs)
6) Other approaches:
a) including laser or infrared light, electro/magnetic/static stimulation, shockwaves,
b) radio waves, topical, and systemic herbal remedies
c) local or systemic herbal remedies
 18.6 ­Evidence for Potential Contributions of Dressings and Wound Applications to Improve Wound Healin 305

surface cells with others which were previously deeper and hence possibly more likely to
behave like those at the base of an acute wound. Secondary analyses of two multicentre
trials designed for other purposes have suggested that better outcomes were observed in
those centres where more vigorous debridement was undertaken [10, 11] but this observa-
tion could obviously have been affected by bias from other differences between care at
individual centres.

18.6.1.2 Autolytic
Most reviews of dressing products refer to three older studies which suggested possible
enhancement of healing associated hydrogel preparations [7]. Two of these three studies
were of weak quality (and one used no statistical analysis). The third was a non‐blinded
RCT. There have been no recent studies.

18.6.1.3 Larvae
It is clear that the topical application of larvae (maggots) will result in fairly rapid removal
of dead tissue and debris from the surface of the wound but it is equally clear that the
debris re‐accumulates when the use of larvae is discontinued. While wound cleaning with
larvae may be a useful prelude to grafting or late wound closure, there is very limited
­evidence that it has a direct effect on healing. There is no strong trial evidence to support
their use [8]. Larvae are also expensive.

18.6.2 Hydrotherapy
The use of a high pressure jet of water to clean the surface of the wound has been promoted
but results are available from only one randomised trial. This showed that although there
was evidence for short term benefit, there was no difference in healing by 12 weeks [12].
Concern has also been expressed that the treatment may spread pathogenic bacteria in water
droplets and hence it is possible that this technique should only be used in dedicated clinical
areas (and hence not appropriate for the review). The consumables are also expensive.

18.6.2.1 Topical Collagenases

The use of topical collagenases has been explored as an approach to cleaning of the wound
surface. There is little evidence to suggest an effect from the four controlled studies that
have been reported. One small study was inconclusive [13]. No benefit was observed in two
more recent studies from the same group [14, 15] as well a third [16].

18.6.3 Antiseptic Preparations

A previous systematic review by the International Working Group on the Diabetic Foot
concluded that there was ‘little evidence to support the use of any one dressing or wound
application in preference to any other in attempts to promote healing of ulcers’ [9] and this
was also the conclusion of an overview of systematic reviews on dressings [17]. On the
other hand, a recent systematic review conducted on the use specifically of antiseptics con-
cluded that there was a possibility that antiseptic preparations may have some benefit on
healing but added that this conclusion was based on ‘low certainty evidence’ [18]. Further
information is clearly needed from high quality trials.
306 18 The Evidence Base for the Choice of Dressings in the Management of Diabetic Foot Ulcers

18.6.4 Honey
The topical application of honey has attracted considerable popular attention although
the precise mechanism of any action is not clear. Earlier data failed to identify any
good evidence of benefit and this was confirmed in another recent systematic review
[19]. This conclusion is reinforced by the very recent finding of no apparent benefit in
another small, non‐blinded RCT [20]. On the other hand one other recent RCT has
suggested that honey‐impregnated dressings may improve healing even though the
median times to healing were surprisingly short (18 versus 29 days) in this study which
included ulcers with relatively large baseline areas [21]. This last study was also weakened
by being unblinded and by its reliance on pre protocol analysis.

18.6.5 Other Components of Dressing Products

The inclusion of alginates in dressing products was once commonplace but there is no
evidence of any benefit in terms of wound healing in DFUs [9]. While early evidence was
available to suspect benefit from carboxymethylcellulose fibres, this has not been con-
firmed [9]. There have been no recent relevant publications.

18.6.6 Acellular Wound Care Products and Skin Grafts

The term acellular wound care product has been used to apply to acellular derivatives of
tissues from either humans or other mammals. Their use is essentially a specialist one
and not appropriate for this review. A recent Cochrane review also concluded that there
was a strong possibility of bias in the majority of studies and the data were insufficient to
draw conclusions relating to long‐term benefit and to cost‐effectiveness [22]. There have,
however, been five recent studies (of which two provided moderately strong evidence
[23, 24] of the effectiveness of graft material derived from amniotic membrane.
This approach remains, however, beyond the scope of this review.

18.6.7 Topical Gases

A number of groups have studied the use of topical oxygen and topical ozone and while
there is some possible evidence of benefit for both, the data are not strong and the use of
gases in this way is unlikely to be adopted in routine wound care. There have, however,
been early reports of the potential benefit of a nitric oxide‐generating dressing product but
the results of a formal study have not been published.

18.7 ­Other Therapies which May Modulate Healing

of Chronic Wounds

18.7.1 Negative Pressure Wound Therapy (NPWT)

Diabetes is a disease in which there are abnormalities of the process of inflammation
and it is thought that the DFU which fails to heal becomes arrested in a pro‐inflamma-
tory phase and fails to mature into the normal proliferative phase of healing. Such
 18.8 ­Summar 307

f­ ailure may be the indirect cause of the marked response of DFUs to the application of
NPWT which is commonly adopted in the routine management of chronic ulcers, espe-
cially after operative debridement. The associated development of often exuberant
inflammatory tissue is commonly observed but the available trials do not clearly describe
(i) the proportion of studied wounds that were post‐operative and (ii) the number of
outcomes that were the result of NPWT alone or the combination of NPWT with
­secondary surgical closure or grafting [9]. It is not clear whether NPWT improves
­healing in chronic wounds that have not undergone surgical debridement. The combi-
nation of NPWT with specific instillation fluids [25] remains a part of specialist care
and is not appropriate for this review.

18.7.2 Dressings which May Modulate Matrix Metalloproteinases

Matrix metalloproteinases (MMPs) have a role in the modulation of newly produced extracel-
lular tissue during the course of normal healing. In chronic wounds, it is thought that expres-
sion of MMPs can be exaggerated and this leads to abnormal tissue breakdown which
interferes with the healing process. One recent good quality, multinational, multicentre RCT
has reported statistically significant benefit from the use of dressings containing sucrose
octasulfate which is thought to both inhibit the action of MMPs and possibly potentiate that
of endogenous growth factors [26]. Although the study population was restricted to those
who were both hard to heal and had peripheral artery disease, the results suggested a
significant improvement in healing and this dressing product may, therefore, have therapeutic
advantage, provided the use of this product is shown to be cost beneficial.

18.8 ­Summary

The overall evidence to justify the use of any particular products in routine wound care for
DFUs is not good. Specifically, there is only weak evidence that the use of topically applied
debriding or antiseptic agents (including those which are widely used, such as iodine, silver,
and honey) have any benefit. There is some weak evidence to support the use of some acel-
lular wound care products but these are not widely used in routine wound care. Topical
negative pressure is widely used but the evidence that it has an impact on healing other than
as an adjunct to surgery is not clear. Good evidence for the use of a preparation which
reduces the activity of MMPs has recently been published and this product may yet be shown
to have a cost‐beneficial role in routine care in a proportion of ‘hard‐to‐heal’ ulcers.
In the absence of good evidence of effectiveness, there is a clear need for the choice of
dressing products by health care professionals to be based largely on acceptability and cost.
The overall expenditure involved is extremely high and a good case can be made for dress-
ings budgets to be based at a level at which the prescribing habits of individual practition-
ers can be scrutinised. There should also be tighter regulation of products and their
adoption onto formularies should be dependent on firm evidence of cost benefit. Those
who advise on dressing choice, should have high quality training on the assessment of
evidence and its importance in routine clinical care. Such advisors should also be respon-
sible for the recommendations which they make. Doctors should have greater insight into
the size of the problem that is caused by DFUs and into its implications for the allocation
308 18 The Evidence Base for the Choice of Dressings in the Management of Diabetic Foot Ulcers

of health care resources.1 Finally, professionals should not be distracted by any hope that
a single dressing or topical treatment will prove to be the ‘must have’ solution to every
DFU. Any single product will only ever be part of the arsenal: just one arrow in the quiver,
and the real key to improving overall care will always lie in the training of professionals
and the uniform adoption of optimal pathways of care of this complex disorder.

­Conflicts of Interest
WJ has received a consultancy fee from URGO Pharmaceuticals.

R
­ eferences

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till March 2018).
2 Guest, J.F., Fuller, G.W., and Vowden, P. (2018). Diabetic foot ulcer management in clinical
practice in the UK: costs and outcomes. Int. Wound J. 15: 43–52. Epub 2017 Dec 15.
3 Guest, J.F., Ayoub, N., McIlwraith, T. et al. (2015). Health economic burden that wounds
impose on the National Health Service in the UK. BMJ Open: e009283. https://doi.
org/10.1136/bmjopen‐2015‐009283.
4 Kerr, M., Barron, E., Chadwick, P. et al. (2019). The cost of diabetic foot ulcers and
amputations to the National Health Service in England. Diabet Med. 36: 995–1002.
5 Jeffcoate, W.J., Bus, S.A., Game, F.L. et al. (2016). Reporting standards of studies and
papers in the prevention and managements of foot ulcers in diabetes: required details and
markers of good quality. Lancet Diabetes Endocrinol. 4: 781–788.
6 Jeffcoate, W.J., Vileikyte, L., Boyko, E.J. et al. (2018). Current challenges and opportunities
in the prevention and amangement of diabetic foot ulcers. Diabetes Care 41: 645–652.
7 Hnchliffe, R.J., Valk, G.D., Apelqvist, J. et al. (2008). A systematic review of he
effectiveness of interventions to enhance the healing of chronic ulcers of the foot in
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8 Game, F.L., Hunchliffe, R.J., Apelqvist, J. et al. (2012). A systematic review of interventions
to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Matab. Res. Rev.
28 (Suppl 1): 119–141.
9 Game, F.L., Apelqvist, J., Attinger, C. et al. (2016). A systematic review of interventions
to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Matab. Res. Rev.
32 (Suppl 1): 154–168.
10 Steed, D.J., Donohoe, D., Webster, M.W. et al. (1996). Effect of extensive debridement and
treatment on the healing of diabetic foot ulcers. J. Am. Coll. Surg. 183: 61–64.
11 Saap, L.J. and Falanga, V. (2002). Debridement performance index and its correlation with
complete closure of diabetic foot ulcers. Wound Repair Regen. 10: 35–359.

1 It should be noted that the data on which this review is based were collated up to end October
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12 Caputo, W.J., Beggs, D.J., DeFede, J.L. et al. (2008). A prospective, randomised controlled trial
comparing hydrosurgery debridement in lower extremity ulcers. Int. Wound J. 5: 288–294.
13 Tallis, A., Motley, T.A., Wunderlich, R.P. et al. (2013). Clinical and economic assessment of
diabetic foot ulcer debridement with collagenase: results of a randomized controlled study.
Clin. Ther. 35: 1805–1820.
14 Motley, T.A., Lange, D.L., Dickerson, J.E. Jr., and Slade, H.B. (2014). Clinical outcomes
associated with sharp debridement of diabetic foot ulcers with and without clostridial
collagenase ointment. Wounds 26: 57–64.
15 Motley, T.A., Gilligan, A.M., Lange, D.L. et al. (2015). Cost‐effectiveness of clostridial
collagenase ointment on wound closure in patients with diabetic foot ulcers: economic
analysis of results from a multicenter, randomized, open‐label trial. J. Foot Ankl. Res. 8: 7.
https://doi.org/10.1186/s13047‐015‐0065‐x. eCollection 2015.
16 Galperin, R.C., Lange, D.L., Ramsay, S.J. et al. (2015). Anti‐inflammatory effects of
clostridial collagenase. J. Amer. Pod. Med. Assoc. 105: 509–519.
17 Wu, L., Norman, G., Dumville, J.C. et al. (2015). Cochrane Database Syst. Rev. 14
https://doi.org/10.1002/14651858.CD010471.pub2.
18 Dumville, J.C., Lipsky, B.A., Hoey, C. et al. (2017). Topical antimicrobial agents for treating
foot ulcers in people with diabetes. Cochrane Database Syst. Rev. (14) https://doi.
org/10.1002/14651858.CD0111038.pub2.
19 Jull, A.B., Cullum, N., Dumville, J.C. et al. (2015). Honey as a topical treatment for wounds.
Cochrane Database Syst. Rev. (6) https://doi.org/10.1002/14651858.CD005083.pub4.
20 Tsang, K.‐K., Wai‐Yung Kwong, E., To, S.‐S., T. et al. (2017). A pilot, randomized, controlled
study of nanoncrystalline silver, Manuka honey, and conventional dressing in healing diabetic
foot ulcer. Evuidence Based Complent. Alt. Med. https://doi.org/10.1155/2017/5294890.
21 Imran, M., Barkaat Hussain, M., and Baig, M. (2015). A randomized, controlled clinical
trial; of honey‐impregnated dressing for treating diabetic foot ulcer. J. Coll. Physicians Surg.
Pak. 25: 721–725.
22 Santema, T.B., Poyck, P.P., and Ubbink, D.T. (2016). Systematic review and meta‐analysis of
skin substitutes in the treatment of diabetic foot ulcers: highlights of a Cochrane
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23 Lavery, L.A., Fulmer, J., Shebetka, K.A. et al. (2014). The efiicacy and safety of Grafix® for
the treatment of chronic diabetic foot ulcers: results of a multi‐centre, controlled,
randomised, blinded, clinical trial. Int. Wound J. 11: 554–560.
24 Zelen, C.M., Serena, T.E., Gould, L. et al. (2016). Treatment of chronic diabetic lower
extremity ulcers with advanced therapies: a prospective, randomised, controlled, multi‐centre
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25 Anghel, E.L., Kim, P.J., and Attinger, C.E. (2016). A solution for complex wounds the evidence
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26 Edmonds, M., Lazaro‐Martinez, J.L., Alfavate‐Garcia, J.M. et al. (2018). Sucrose octasulphate
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(explorer): an international, multicentre, double‐blind, randomised controlled trial. Lancet
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 311

19

Pathogenesis of Charcot Neuroarthropathy and Acute

Management
N.L. Petrova and Michael E. Edmonds
Diabetic Foot Clinic, King’s College Hospital NHS Foundation Trust, London, UK

19.1 ­Introduction

Charcot neuroarthropathy (CN) or Charcot foot is a devastating complication of diabetic

neuropathy, associated with an extensive bone and joint destruction, severe foot deformity,
increased risk of ulceration, infection, and sometimes amputation. In the last decade,
­significant progress has been made in our understanding of the natural history of CN
including in particular the enhanced inflammatory response to trauma and bone destruc-
tion on the background of neuropathy. There has been an improved recognition of CN
globally with a notable rise in reported cohorts of patients. Moreover, with the predicted
global increase in the prevalence of diabetes [DM] the burden of neuropathy and its related
adverse complications including CN is also expected to rise (https://diabetesatlas.org/
IDF_Diabetes_Atlas_8e_interactive_EN/.
This chapter is divided into two parts. The first part will describe the current progress
which has been made to illustrate the interaction between neuropathy, inflammation, and
bone destruction, as key features in the pathogenesis of CN. The second part will describe
the presentation and current standards of acute management of the Charcot foot.

19.2 ­Pathogenesis of CN
19.2.1 From Fundamental Theories to a Novel Understanding
of the Diabetic Charcot Foot
Historically, two classical theories have been put forward to explain the pathogenesis of
CN. The first one, proposed by Charcot himself (the ‘neuro-vascular’ or French theory)
explained that loss of sympathetic control due to a spinal cord lesion could lead to ­abnormal
trophic regulation leading to vasodilation and increased blood flow resulting in increased
bone weakening, bone breaking, and subsequent destruction. The second one, supported
by Volkman and Virchow (‘neuro-traumatic’ or German theory) emphasised the role of

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
312 19 Pathogenesis of Charcot Neuroarthropathy and Acute Management

neuropathy and repetitive trauma, triggering soft tissue swelling, and bone and joint
destruction. Although previously seen as competing, these two concepts are now consid-
ered complementary as neither can fully explain the modern presentation of CN. Both
theories encompass essential triggers of the neuroarthropathy including neuropathy and
aberrant mechanical forces, trauma and inflammation, bone fracture, and destruction.
These classical precipitating and predisposing factors, together with novel cellular path-
ways accounting for the interaction between neuropathy, inflammation, and increased
osteoclastic activity encompass the current understanding of the pathogenesis of the
Charcot foot [1].

19.2.2 The Clinical Impact of Neuropathy on Bone

Improved understanding of the skeletal effects of the nervous system on bone remodelling
and fracture healing of normal and damaged joints is essential to understand the impact of
neuropathy, as a crucial factor in the predisposition to CN [2].
Neuropathy is associated with increased risk for pathological fractures, and delayed and
impaired fracture healing [3]. Patients with severe sensory and autonomic neuropathy
have diminished cortical bone mass in both hands and feet when compared with controls
and sustain more frequently metatarsal fractures [4]. Patients with type 1 DM and neuropa-
thy have decreased bone mineral density (BMD) in the femoral neck and distal limb [5] and
reduced BMD in the calcaneus [6]. In type 2 DM, neuropathy is associated with increased
biomechanical pressures, impaired balance, gait abnormalities, and increased risk of falls
which can also lead to pathological fractures (despite normal or raised BMD) [7, 8].
Osteopenia and neuropathy in patients with type 1 DM is associated with increased risk of
foot fractures. Consequently, both patients with type 1 and type 2 DM are susceptible to
developing CN [7].
In addition to pathological fractures, neuropathy contributes to delayed and impaired
fracture healing [9]. In a series of patients with lower extremity fractures, time to healing
was more than double in subjects with DM compared to subjects without DM (8.2 versus
3.6 months) and 3 out of 9 subjects with DM had a fracture non-union [10, 11]. In addition
to a significant delay in time to union, DM was associated with an increased incidence of
non-union and pseudoarthrosis.
A study which assessed outcomes of ankle fractures in patients with uncomplicated
­versus complicated diabetes showed that the odds ratio for revision surgery/arthrodesis was
5.0 and the odds ratio for noninfectious complications (malunion, non-union or CN) was 3.4
in those with complicated diabetes mellitus [12]. More importantly, due to the underlying
neuropathy, most of the complications were unrecognized by the patients themselves [12].
An intact nervous system is essential for fracture healing. Aro et al. studied callus forma-
tion in tibial fractures of rats [13]. Non-unions were created in the tibia in rats rendered
neuropathic by transection of the sciatic nerve. The removal of periosteal mechanoreceptors
caused a non-union in the tibia in insensate limbs led to incomplete maturation of new
bone [13]. Moreover, sciatic nerve transection induced a large, but mechanically insufficient
fracture callus, in rat tibia after 25 days of fracture [14]. Thus, intact neuronal regulation is
essential for both the quantity and the quality of callus formation. A similar hypertrophic
response to injury has been observed in CN patients [15].
 19.2 ­Pathogenesis of C 313

19.2.3 Neuropeptides
Neural control is essential for bone development, growth, turnover and repair. The skeleton
is abundantly innervated and in vitro experiments have demonstrated that several neuro-
peptides regulate osteoclast and osteoblast function. Substance P and calcitonin gene-
related peptide (CGRP) are essential neuropeptides for early skeletal development and
fracture repair [16]. They are potent vasodilators and have an osteotrophic effect.
In bone, CGRP-containing sensory nerves are the most abundant nerves and CGRP is
found in unmyelinated (C-type) and small myelinated (A-type) primary sensory neurons.
The density of CGRP fibres is increased near the sites of postfracture osteogenesis (healing
callus) [17]. Numerous thin, short CGRP-positive fibres were identified one week post-­
fracture with a peak in CGRP immunoreactivity at week three [17]. Interestingly, there was
a 27-fold increase and 36-fold increase in CGRP immunoreactivity in a straight and angular
fracture respectively as compared to intact tibia [17]. Moreover, the highest presence of
CGRP positive fibres was noted at the site of maximum bone formation in fracture healing
[17]. CGRP is essential for the activation of osteoblastic CGRP receptors and results in
enhanced osteoblast proliferation in vitro, whereas evidence from bone marrow macrophage
cultures has shown that CGRP inhibits osteoclastogenesis and bone resorption [18].
In neuropathy, the neuronal regulation of bone repair is impaired possibly due to lack of
CGRP. A recent immunohistological study showed a trend towards reduced expression of
CGRP in CN bone specimens compared with controls [19]. It is plausible that neuropathy-
related CGRP deficiency may lead to impaired osteogenesis, delayed fracture healing, and
enhanced osteoclastic activity. This neurogenic alteration in normal bone homeostasis can
result in bone resorption and destruction.
In addition to lack of CGRP, a decreased expression of endothelial nitric oxide synthase
has been noted in CN bone specimens [19]. This enzyme generates the vasoprotective
molecule nitric oxide which contributes to the proliferation and differentiation of osteo-
blasts. Nitric oxide also induces apoptosis of pre-osteoclasts and decreases the resorptive
action of the mature osteoclasts [20]. Abnormal endothelial nitric oxide synthase activity,
and consequently decreased nitric oxide levels, may lead to bone loss ultimately resulting
in CN [19].
In patients with neuropathy, the lack of neuropeptides, and their modulatory effect on
bone may lead to abnormal response to trauma, uncontrolled inflammation, and bone
­fracture ultimately resulting in CN.

19.2.4 Anomalous Inflammatory Response to Trauma in CN

In CN, the process of pathological bone destruction is initiated by trauma, which may or
may not be perceived by the patient due to the underlying neuropathy. Johnson in his clas-
sical review described foot fracture as the ‘harbinger’ of CN [21]. Recent observations of the
natural history of CN using novel imaging modalities indicate that the inflammatory
response to trauma is associated with the presence of ‘hot spots’ on a three-phase diphos-
phonate bone scan and bone marrow oedema on magnetic resonance imaging (MRI) often
linked with microfracture [22]. The repair reaction to injury is abnormal due to underlying
neuropathy and uncontrolled inflammation [1, 2].
314 19 Pathogenesis of Charcot Neuroarthropathy and Acute Management

Studies of the physiology of the cholinergic anti-inflammatory pathway show that the
nervous system, via the inflammatory reflex of the vagus nerve, can control cytokine release
in response to trauma [23]. Afferent signals carried in the vagus nerve can activate an
­efferent response that inhibits cytokine release (known as cholinergic anti-inflammatory
pathway) [23]. It is mediated primarily by the nicotinic acetylcholine receptor on tissue
macrophages and leads to decreased production of pro-inflammatory cytokines and thus
prevents tissue injury [24].
In contrast, the inflammatory response to trauma in the Charcot foot consists of a dispro-
portionate release of cytokines from activated monocytes. The increased concentrations of
pro-inflammatory cytokines (tumour necrosis factor-α [TNF-α], interleukin-1β [IL-1β],
and IL-6) and reduced secretion of anti-inflammatory cytokines (IL-4 and IL-10) [25], lead
to uncontrolled inflammation. Alterations of spontaneous and inducible cytokine produc-
tion were noted only in the active stage of CN [25]. In addition, the latter was characterised
by an up-modulation of surface molecules in monocytes and increased resistance to
­apoptosis [25]. These pro-inflammatory changes enhance the cell to cell communication.
In CN, inflammatory modulated cells release extra-cellular vesicles into their surrounding
environment [26]. Micro-particles derived from blood samples from CN patients have an
increased content of the pro-inflammatory cytokines granulocyte colony-stimulating fac-
tor, granulocyte-macrophage colony-stimulating factor, IL-1 receptor antagonist and IL-2
[26]. When added to cell culture, these macro-particles lead to increased expression of their
downstream targets and increased differentiation of monocytes into osteoclasts, ultimately
resulting in increased osteoclastic activity [26].

19.2.5 What Is the Link Between Inflammation and Bone Resorption

in CN: Evidence from Clinical and In Vitro Studies and Histological Analysis
of Bone Specimen
Data from clinical studies demonstrate that the serum concentrations of TNF-α and IL-6
are raised in the active stage of CN and they positively correlate with serum biochemical
markers of bone resorption [27]. The increased osteoclastic mediated bone resorption in
the active Charcot foot is not coupled with osteoblast bone formation, resulting in negative
bone balance. Recent advances in cellular biology has led to an improved understanding of
the mechanisms of osteoclast activation in CN. Studies have focused on receptor activator
of nuclear factor-kβ ligand/osteoprotegerin (RANKL/OPG), a key signalling pathway of
both physiological and pathological osteoclastogenesis.
Application of an in vitro osteoclast culture assay has confirmed that activated osteo-
clasts are key drivers of the pathological bone destruction of CN. Osteoclasts generated
from monocytes isolated from Charcot patients and cultured on bovine or dentine bone
discs exhibited increased resorbing activity in response to the osteoclast activator RANKL
[28, 29]. This resorption was blocked by the addition of excess concentrations of OPG, con-
firming the role of RANKL as an activator of osteoclastic activity in acute CN [28, 29].
Further studies, using a novel application of surface profilometry, revealed a notable differ-
ence in the way Charcot osteoclasts exert their resorbing activity [30]. In Charcot cultures,
resorption pits on bovine bone discs were deeper and wider with increased area of resorp-
tion both on the surface and under the surface [30]. The addition of neutralizing antibody
 19.2 ­Pathogenesis of C 315

to TNF-α (anti-TNF-α) led to significant reduction of the area of resorption and normaliza-
tion of the erosion pit profile in Charcot patients [31]. The observed differences in the type
of resorption before and after the addition of anti-TNF-α suggest that TNF-α enhances the
resorptive behaviour of osteoclasts generated from Charcot patients and these highly active
osteoclasts are capable of extensive lacunar resorption with aberrant pit morphology and
geometry. This increased osteoclastic activity may be due to cathepsin K upregulation,
which requires further studies, as this may provide scientific basis for novel intervention
with cathepsin K inhibitors [31].
In patients with CN, osteolysis is regional and limited to the affected Charcot foot.
Trauma and (micro-) fracture induce the production of pro-inflammatory cytokines.
Inflammatory modulated endothelium, as well as upregulated RANKL-induced monocyte
migration, leads to enhanced differentiation of osteoclastic precursors into highly aggres-
sive osteoclasts with extensive resorbing activity. These observations support the recent
hypothesis of the pathogenesis of CN which proposed inflammation as a modulator of
osteoclastic activity [1].
Further evidence from histological studies in CN confirmed that excessive osteoclastic
activity occurs in an inflammatory milieu with increased expression of pro-inflammatory
cytokines. Analyses of bone specimens collected from patients with Charcot foot showed
a disproportionate increase in osteoclasts to osteoblasts [32, 33]. Bone samples from CN
patients appear disorganised and immature, displaying myxoid tissue within inflamma-
tory infiltrates. Also, there was an increase in the number of Howship’s lacunae,
­osteoclasts, and woven bone, indicative of increased osteoclastic activity. In CN samples,
in contrast to controls, the number and the volume of bone trabeculae, as well as the num-
ber of osteocytes were decreased. Empty lacunae were also reported [32, 33]. In bone
specimens in CN, osteoclasts demonstrated immunoreactivity for IL-1, IL-6, and TNF-α
[32]. The observed osseous abnormalities suggest that, in CN bone, samples display
increased bone resorption with an impaired reparative properties taking place in an
inflammatory environment.

19.2.6 Why Only a Small Proportion of Patients with Neuropathy Develop

CN – Is there a Genetic Predisposition?
The observation that only a small proportion of patients within the vast majority of patients
with diabetic neuropathy develop CN suggests a possible involvement of genetic factors.
Two studies have examined the association between OPG gene polymorphisms and CN.
The first study was conducted in a Caucasian Italian population including 59 subjects with
CN, 41 subjects with diabetic neuropathy without CN, and 103 healthy controls [34].
A strong association between OPG G1181C and T245G polymorphisms, located in the
exon 1 region and promoter region, respectively, were reported in CN. In patients with
diabetic neuropathy, these polymorphisms potentially increase the risk of developing
Charcot foot disease [34].
The second study was conducted in a Caucasian Polish population including 54 patients
with CN, 35 subjects with diabetic neuropathy but no CN, and 95 healthy controls. In addi-
tion to significant differences in the frequencies of 1181G>C polymorphism between the CN
group and the control group, this study also noted significant differences in the frequencies
316 19 Pathogenesis of Charcot Neuroarthropathy and Acute Management

of 950T>C polymorphism between the CN group and the control group, as well as between
the group with neuropathy but no CN and the control group [35].
A further study of genetic markers extended the analysis of OPG polymorphisms to
RANKL and RANK polymorphisms, as key cytokines of osteoclast regulation [36]. A total
of 10 polymorphisms in 3 genes: OPG (5 variants), RANKL (3 variants) and RANK
(2 ­variants) were studied in samples collected from 260 patients, including patients with
CN, diabetic neuropathy, and diabetes controls. Consistent with previous reports, this
study confirmed that CN was associated with significantly higher genotype frequency for
OPG1181G/C [34, 35]. In addition, it was also noted that OPG 245T/G (rs3134069) and
OPG 1217C/T (rs3102734) polymorphisms co-occur in patients with CN [36]. Moreover,
both CN and diabetic neuropathy were associated with RANKL gene polymorphisms
including the T allele in RANKL 290C/T and 643C/T as well as the C allele in 693G/C [36].
These recent observations reveal a distinctive gene profile in patients with CN and
neuropathy.

19.3 ­Acute Management of CN

19.3.1 Presentation
The active Charcot foot typically presents as a red hot swollen foot often set off by trauma. The
initial onset of CN may remain unnoticed by the patient due to underlying neuropathy. This
often leads to a delayed presentation. In a patient with a suspected Charcot foot, a detailed
medical history regarding a recent episode of trauma, surgical debridement, revascularisation
or mobilization after prolonged bed rest should be promptly collected. Other causes of a red
hot swollen foot should be ruled out (Chapter 30).
Unilateral foot swelling is frequently reported by patients (Figure 19.1a–c). The extent of
swelling varies from subtle to a grossly swollen foot. It is more pronounced after ­continuous
weight-bearing and can subside partially after bed-rest. The affected foot appears redder in
Caucasians or discoloured in ethnic minorities (Figure 19.1a–c). Some patients report dull
ache or discomfort of the foot although, in the majority of cases, CN is painless. Overall,
trauma triggers excessive inflammation, fracture, bone fragmentation, and joint destruction,

(a) (b) (c) (d)

Figure 19.1 Clinical presentations of CN in diabetes. Subtle (a) and pronounced (b) unilateral foot
swelling, skin discolouration (c) and foot deformity (medial convexity -d) in cases presenting with
active CN.
 19.3 ­Acute Management of C 317

and ultimately leads to foot deformity, i.e. the Charcot foot (Figure 19.1d). Acute Charcot
foot is often confused with cellulitis due to the presence of oedema and erythema. The over-
whelming majority of diabetic foot infections are associated with a contiguous wound, and
in the absence of a wound history, infection is unlikely and a Charcot foot should be sus-
pected. The elevation test may also be useful in the setting. Patients with infection typically
do not have resolution of erythema with five minutes of elevation, whilst the erythema asso-
ciated with CN generally resolves with elevation.

19.3.2 Investigations and Diagnosis

A high index of suspicion is needed to make the earliest diagnosis and institute prompt
management. The active Charcot foot is significantly warmer compared with the contralat-
eral foot. Skin foot temperatures are assessed with infrared thermometry at corresponding
sites between the affected and contralateral foot. The temperature difference between feet
is usually recorded for the forefoot, midfoot and hindfoot. Alternatively, in the absence of
skin thermometer, the heat can be detected by comparative palpation of the affected and
contralateral foot with the back of the hand.
The diagnosis of CN is primarily based on clinical findings, as at the present time, there
are no established biochemical disease markers. The acute inflammatory response in CN is
characterised by a normal to mild rise of inflammatory markers, the serological concentra-
tions of which are often below the concentrations noted in infection [37, 38].
Modern imaging is considered as the cornerstone for diagnosis [39] and should be carried out
in cases with clinically suspected Charcot feet. Conventional radiography is the first line of
investigation. Patients should be referred for weight-bearing foot and ankle radiographs (prefer-
ably straight, oblique, and lateral foot X-rays, and straight and lateral ankle views). These projec-
tions allow full assessment of the foot and ankle abnormalities, related to the Sanders and
Frykberg’s anatomic classification of CN [see Chapter 20] [40]. Close inspection of the tarso-
metatarsal joints (pattern II), cuneonavicular, talonavicular, and calcaneocuboid joints (pattern
III) should be performed as these sites are affected in almost 80% of the cases [40]. Rarer pres-
entations include the involvement of the metatarsal–phalangeal joints (pattern I), the ankle
joint (pattern IV), and fracture of the posterior process of the calcaneum (pattern V) [40].
Advances in imaging techniques have improved the recognition of the stage 0 Charcot foot
with normal X-ray but positive MRI [41]. In the absence of occult radiographic ­findings, MRI
reveals soft tissue swelling, bone marrow oedema, microfractures, and bone bruising [41].
Further imaging modalities include a technetium methylene diphosphonate (Tc 99 m MDP)
bone scan [42]. The latter shows focal areas of increased uptake of radionuclide indicative of
early bone damage. Recently, in addition to the conventional bone scan, ­single-photon emis-
sion computer tomography has been used in the assessment of pathological osteolysis in CN.

19.3.3 Treatment
Offloading by means of a below knee total contact cast (TCC) together with crutches is the
mainstay of CN management and should be initiated in every patient suspected of having
a Charcot foot. The cast offloads the foot and reduces mechanical forces, oedema, and
inflammation [40]. It also redistributes the plantar pressure to a greater surface area as well
318 19 Pathogenesis of Charcot Neuroarthropathy and Acute Management

as limits bone and joint destruction [40]. Timely intervention of stage 0 Charcot foot could
arrest the development of deformity and keep the X-ray normal [42]. Patients presenting
with stage 1 active Charcot foot (X-ray positive and MRI positive) also require offloading
with a TCC to heal fractures, limit subsequent bone and joint destruction and arrest dete-
rioration of foot deformity. The ultimate goal of the non-surgical treatment is to achieve a
plantigrade stable foot, which at resolution can be accommodated in bespoke footwear.
Offloading modalities often used in clinics include treatment with a bespoke TCC or
removable off-the-shelf cast walkers. Treatment with TCC requires an experienced health
care professional trained in cast applications as well as an established safety network
(including out of hours support). To minimize any cast related complications, patients
should be informed about potential risk of TCC treatment at initiation of casting therapy
and should be encouraged to present to clinic as quickly as possible [44, 45]. Treatment
outcomes depend not only on the expertise in managing CN patients but also on the sub-
ject’s compliance, which may be lower when using a removable device. Thus, in centres,
where treatment with non-removable TCC is not an option, it is possible for off-the-shelf
devices to be made non-removable to improve compliance [46].
Reduction of foot swelling and skin temperatures are traditionally used to assess the pro-
gression of CN from active into an inactive stage. A recent study reported the use of blood
flow measurements as a method to assess disease activity. In a small cohort of patients with
active Charcot foot, patients were treated in a well-padded non–weight-bearing cast until
the Doppler spectrum patterns of the first dorsal metatarsal artery normalized [47].
In addition to clinical assessment, repeated MRI imaging has been used in the follow-up
of CN [48]. Reduction of bone marrow oedema and fracture healing could be graded by a
recently developed semi-quantitative-scoring proforma [49].
There is an urgent need of reliable objective methods to confirm resolution of CN which
could aid the overall management of these patients, and reduce unnecessary prolonged
duration of casting and also relapse. At the current time it remains difficult to determine
when the active phase of CN becomes clinically quiescent.

19.3.4 Pharmacological Therapies

At present, evidence to support the use of pharmacological therapies in the management
of CN is weak [39]. Experience with anti-resorptive therapies (bisphosphonates and calci-
tonin) and anabolic therapies (recombinant parathyroid human hormone) used in addition
to casting therapy have been limited to clinical trials in small cohorts of patients with CN.
Initial experience with a single dose of RANKL antibody seems promising, as treatment
with this agent leads to a faster fracture resolution in a small cohort of patients [50]. The
benefit of new biologic agents in the management of CN is yet to be established.

19.4 ­Conclusions

Developments in cellular and molecular biology have advanced our understanding of the
mechanisms of the pathological osteolysis of the diabetic neuropathic foot. A systematic
approach in the assessment of the red hot swollen foot has enhanced the recognition of CN
   ­Reference 319

and early diagnosis. Casting therapy remains the mainstay tool in the management of this
condition. Timely intervention can arrest deformity and keep the X-ray normal. Research
into novel biomarkers to monitor disease activity and the response to casting therapy is of
paramount importance. A novel therapeutic approach is urgently needed for an improved
outcome of patients with this condition.

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 323

20

Surgical Reconstruction of the Charcot Foot

George Liu, Katherine Raspovic, and Dane K. Wukich
Department of Orthopaedic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA

20.1 ­Introduction

Charcot neuroarthropathy (CN) is a non‐infectious destructive process that most ­commonly

affects the foot and ankle in patients with diabetes mellitus (DM). As a result of inflam-
mation in patients with neuropathy, the pedal architecture is subject to fractures, disloca-
tions, and fracture/dislocations (see Figure 20.1a–c) [1]. Whilst the estimated prevalence
of CN in patients with DM is reported between 0.08 and 13%, the true prevalence is
unknown likely due to misdiagnosis or delayed diagnosis [2–4]. An estimated 33% of
patients with CN are not accurately diagnosed at the time of initial presentation [5]. The
delay in diagnosis of acute CN has been shown to increase the need for surgical care by
53% compared to patients with earlier recognition [6]. Whilst the primary concern of
most patients with CN is lower extremity amputation (LEA), the annual amputation risk
is relatively low with a reported 2.72 per 100 patients on survivorship scale [7, 8]. Once a
foot ulcer develops in a patient with CN the risk of amputation increases by a factor of
five [9]. CN in patients with diabetes increase the likelihood for foot ulceration more than
any other condition (see Figure 20.2). [10, 11] Though a majority of CN can be success-
fully managed conservatively, approximately 25% of patients will require operative man-
agement to address unstable or rigid deformities that increase the risk for ulceration [12].
The goal of surgical intervention for CN is to create an ulcer free, stable, plantigrade,
braceable limb.

20.2 ­Indications for Surgical Reconstruction

Despite nonsurgical treatment, approximately 4–51% of patients with CN will require

surgical intervention [7, 12–14]. The indications for surgical reconstruction of CN are
for non‐healing ulcers, pain, and eradication of infection (soft tissue and osteomyelitis).
Typically, patients who require surgery have unstable joint deformities, malunions

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
324 20 Surgical Reconstruction of the Charcot Foot

(a) (b)

(c)

Figure 20.1 Radiographic anterior–posterior (a) and lateral (b) view demonstrates talonavicular
and subtalar dislocation from CN with severe nonplantigrade deformity (c).

Figure 20.2 Plantar ulceration results from peripheral neuropathy and deformity from CN.

causing bony prominences, and biomechanical alterations resulting in a non‐­plantigrade

foot. The goals of operative intervention for CN therefore, are to achieve a stable, plan-
tigrade foot, that is free of infection and ulceration, and to reduce the risk for recurrent
ulceration.
 20.3 ­Radiographic Predictors for Ulceratio 325

20.3 ­Radiographic Predictors for Ulceration

The most common area for breakdown is the midfoot area (Sanders/Frykberg Pattern 2 and
3 and Brodsky Type 1; see Figure 20.3) comprising 48–83% of all CN [4, 7, 12, 13, 15–17].
The arch is the site of lever arm forces transmitting loads to the metatarsophalangeal joints
for the push‐off phase of gait. Nonenzymatic glycosylation of the Achilles tendon and
resultant contracture increases pressure in the forefoot. During the stance and push off
phases of gait excessive lever arm shearing forces are transmitted though the midfoot,
­contributing to collapse of the arch.
Location of CN deformity has been shown to determine the likelihood for surgical
­reconstruction. A systematic review of surgical reconstruction for CN reported that the
most common anatomical sites requiring surgery were midfoot (43.5%), ankle (33.8%) and
hindfoot (26.1%) [18, 19].
For midfoot deformities, the nonplantigrade foot is characterised by a deformity in which
weight transmitted through skin that is not normally weightbearing [20]. For example, the
skin at the apex of the arch was not meant to bear weight. In a typical rocker bottom deform-
ity with collapse that skin becomes subjected to increased plantar pressure and shear, leading
to break down. Similarly, medial and lateral skin above the glabrous junction was not meant
to bear weight and is prone to ulceration when subjected to sustained pressure and shear.
Radiographic measures are commonly used to assess the source of malalignment in the foot.

Sanders/Frykberg Ill

Sanders/Frykberg IV
Sanders/Frykberg ll

Sanders/Frykberg l

Brodsky Type 3b

Sanders/Frykberg V

Brodsky Type 3b Brodsky Type 2 Brodsky Type 1

Figure 20.3 Sanders and Frykberg Anatomic Classification for Charcot Osteoarthropathy: Pattern 1
involves distal and proximal interphalangeal and/or metatarsophalangeal joints; Pattern 2 involves
tarsometatarsal joints (Lisfrancs); Pattern 3 involves cuneonavicular, talonavicular, and/or
calcaneocuboid joints; Pattern 4 involves ankle and/or subtalar joint; Pattern 5 involves calcaneus.
Brodsky Anatomic Classification of Charcot arthropathy: Type 1 involves midfoot (tarsometatarsal
and/or cuneonavicular joint); Type 2 involves hindfoot (subtalar, talonavicular and/or
calcaneocuboid joints; Type 3A involves the tibiotalar joint; Type 3B involves a calcaneal tuberosity
fracture. Source: Sanders and Frykberg [2] and Brodsky [15]
326 20 Surgical Reconstruction of the Charcot Foot

Figure 20.4 Negative cuboid height is demonstrated with cuboid descending below the line
between the calcaneal tuberosity to the fifth metatarsal head.

The hindfoot–forefoot angle is assessed with a line between the anterior posterior talo-
calcaneal angle and a line bisecting the middiaphyseal axis of the second metatarsal. The
anterior posterior talar–first metatarsal angle is measured from the line bisecting the
talar neck and line bisecting the first metatarsal [21, 22]. The medial column alignment
is evaluated with the lateral talar–first metatarsal angle and medial column height from
the reference line (plantar aspect of the calcaneus to the fifth metatarsal head) to the
metatarsal cuneiform joint. The lateral column alignment is evaluated with the lateral
fifth metatarsal–calcaneal angle [23].
Two studies evaluated radiographic measures as predictors for ulceration of midfoot CN.
Bevan et al. [24, 25] demonstrated that the lateral talar‐first metatarsal angle of less than
27° was significantly increased the risk for plantar midfoot ulceration. Wukich et al. [25]
reported that 24% of midfoot deformities with a talar–first metatarsal axes less than 27° on
weightbearing lateral view and 80% with a negative cuboid height had a plantar midfoot
ulceration (see Figure 20.4). Both studies showed no significant associations between
transverse plane deformities as measured by the anterior posterior views with foot
­ulcerations [24, 25].

20.4 ­Timing of Surgery

Historically, operative intervention during the acute inflammatory stage of CN was avoided
due to significant oedema and osteopenia that increases the perceived risk for wound
­complications and fixation failure [1]. However, in cases of acute CN joint subluxation/­
dislocation that are unstable or result in deformities that would not be successfully managed
with traditional immobilization with non‐weightbearing, operative measures may be
­necessary. Two reports demonstrate that operative intervention in the acute stage CN
 20.6 ­Glycemic Contro 327

joint ­subluxation/dislocation may be considered in the absence of fragmentation on radio-

graphs [26, 27]. Simon et al. [28] reported a small case series of successful primary arthrode-
sis during the acute stage CN with fragmentation. Sundararajan et al. [29], in their
retrospective review of 33 patients tibiotalocalcaneal fusions with intramedullary hindfoot
nail for CN of the ankle joint revealed no significant variation of fusion rates between the
developmental (acute), coalescence (quiescent), or reconstruction stages.

20.5 ­Preoperative Medical Workup

20.5.1 Assessment for Peripheral Arterial Disease

Assessment of pulsatile flow to the foot should be assessed clinically with palpable pulses,
skin turgor, presence of cutaneous hair, and capillary fill time. However, palpable pulses
may be palpated in the presence of peripheral arterial disease (PAD) due to vasomotor
dysfunction from autonomic neuropathy and artery being supplied by compensatory col-
lateral flow. Approximately, 49.8% of patients with diabetic foot disease (CN, foot ulcers,
infection) are identified with PAD [30]. Patients without a pedal pulse were 4.9 times
more likely to have PAD compared to patients with pulses [30]. Defining PAD as an ankle
brachial index (ABI) of <0.9 or a toe brachial index (TBI) of <0.7 on either extremity,
Wukich et al. [31] reported a 40% prevalence of PAD in the patients with CN. The vast
majority of patients with CN did not have critical limb ischaemia (87%). ABIs may be
falsely elevated secondary to medial artery calcinosis (MAC), particularly in patients with
diabetic neuropathy and end stage renal disease, therefore TBIs are a more accurate
means of quantitating gross arterial blood flow as MAC typically spares the digital arter-
ies. Toe pressure ≥ 60 mmHg is considered adequate perfusion for healing in surgical
reconstruction.

20.6 ­Glycemic Control

Hyperglycaemia in DM has been shown to impair host immunity by decreasing of chemo-

taxis of leukocytes, phagocytosis, and bactericidal action [32, 33]. Perioperative hypergly-
caemia has been shown to be an independent risk factor for surgical site infection (SSI) in
patients undergoing musculoskeletal surgery with and without diabetes [34–38]. Patients
with DM undergoing foot and ankle surgery with a perioperative glucose exceeding 200 mg/
dl (11.9%) had had a significantly higher SSI rate compared to patients whose glucose did
not exceed 200 mg/dl (5.2%)[P = 0.03]. [37] The likelihood for perioperative hyperglycae-
mia >200 mg/dl increased by 4.15‐fold in patients with CN and 2.41‐fold in patients with
peripheral neuropathy [37].
Haemoglobin A1c (HgA1c) measuring long‐term glucose control has been a known risk
factor for unfavourable outcomes for both orthopaedic and nonorthopaedic surgery
[38–47].
The American Diabetes Association’s current practice recommendations indicated that
surgery should be avoided for patients with HbA1c greater than 7% though criteria for this
328 20 Surgical Reconstruction of the Charcot Foot

threshold was not clearly delineated [48]. Jupiter et al. [45] reported that infection rates for
patients with diabetes undergoing foot surgery that experienced a complication and those
who did not was a difference of HgA1c of 8.26% and 7.17%. This was found to be a statisti-
cally significant difference. Wukich et al. [38] in their series of patients with diabetes
undergoing foot and ankle surgery found that the likelihood for surgical site infection was
2.5 times greater in patients with an HgbA1c greater than 8% compared to those that were
less than 8%. Shibuya et al. [49] reported a significant association in patients with HgA1c
greater than 7% with bone healing complications such as malunions, delayed unions, or
nonunions.
Both long and short‐term glycemic control is necessary to reduce the risk for periopera-
tive and long‐term complications of foot and ankle surgery in patients with diabetes.
A multidisciplinary approach to optimal glycemic control is recommended as part of the
preoperative work up for patients undergoing CN reconstruction [50].

20.7 ­Vitamin D

Vitamin D levels have been reported to be statistically lower in patients with diabetes with
and without CN compared to patients without diabetes [51]. Vitamin D deficiency has
been implicated in the development of CN [52]. Lower vitamin D levels lead to decreased
calcium absorption from the intestine and hypocalcaemia. As a result, parathyroid
­hormone secretion depletes calcium from bones, contributing to decreased bone mineral
density. In the setting of osteoclastogenesis, weakened bone is vulnerable to both minor
and major injury. Addressing vitamin D deficiencies is recommended prior to reconstruc-
tive surgery of CN.

20.8 ­Renal Function

The prevalence of renal impairment and end‐stage renal disease (ESRD) in CN is high
[53–56]. Approximately, 30% of patients with CN have ESRD [56]. One report found that
renal failure increased the risk of CN by two fold [55]. It is uncertain whether this asso-
ciation between renal disease and increased prevalence of CN is a manifestation of micro-
vascular complications or impairment of bone metabolism.

20.9 ­Procedures/Outcome Studies

Though there is no consensus regarding surgical management guidelines for operative

intervention for CN, recommendations have been primarily generated from case series
and expert opinion [18, 19]. Procedural selection for CN is based upon location and
­magnitude of the deformity, joint stability, presence of ulceration, and presence of
osteomyelitis.
 20.9 ­Procedures/Outcome Studie 329

20.9.1 Exostectomy
Due to the low technical demands and shorter convalescent period of nonweightbearing,
exostectomies are the preferred procedure for isolated osseous prominences of CN without
significant deformity. Simple exostectomies are often indicated for ‘rocker bottom’ CN
deformities as the site of abnormal focal plantar pressures with the presence of an ulcer or
preulcerative lesion [57]. Several investigators have reported successful outcomes of exos-
tectomies for CN midfoot deformities and plantar ulcerations citing 66.7– 100% overall
healing rates [5, 12, 57–61]. Rosenblum et al. [61] reported on exostectomies in 31 patients
(32 ft) with chronic plantar midfoot ulcerations from CN citing a 51% initial success rate
with an 89% overall success rate after a secondary procedure on a cumulative life‐table
analysis. Laurinaviciene et al. [59] later reported similar findings of 55% initial success
with index procedure and an 82% overall success rate after secondary procedure in their
consecutive series of exostectomies in 19 patient and 20 ft with CN plantar midfoot ulcera-
tions. Other reports identified location of exostosis as a risk factor for healing. Catanzariti
et al. [58] reported 92% healing rates for medial column exostectomies compared to 37.5%
for the lateral column. Laurinaviciene et al. [59] cited a 66.7% ulcer recurrence after exos-
tectomies for lateral column osseous prominences.

20.9.2 Realignment Arthrodesis

Realignment procedures are indicated in cases of severe or unstable CN deformities and
where exostectomies fail to provide sufficient offloading to sites of ulceration.

20.9.2.1 Midfoot
The midfoot is the most common area affected by CN [7, 12, 13, 16, 17]. The midfoot
­consists of the tarsometatarsal and transverse tarsal joints, which function as a rigid lever
arm to efficiently transfer weight from the heel to the metatarsal heads during the pushoff
phase of gait. This confirms the earlier consideration. With midfoot breakdown, the lever
arm forces transfers from the metatarsal heads to the midfoot creating a source of focal
pressure and subsequent tissue breakdown.
Midfoot CN deformity correction is indicated in patients with a nonplantigrade foot that
is not amenable to bracing. Radiographically, these feet typically have a noncolinear lateral
talar first metatarsal axis and/or have a negative cuboid height [20, 24, 25]. Realigning and
stabilizing the medial and lateral columns of the midfoot is necessary to restore plantigrade
foot and relieve bony prominences. The surgical goals should be to re‐establish the AP talar
first metatarsal angle, the lateral talar first metatarsal angle, and to restore cuboid height. In
most midfoot CN cases, equinus is present and restoration of ankle alignment is necessary
as well with tendon lengthening. Two patterns of midfoot dislocation have been described.
Dorsal lateral subluxation of the talonavicular joint is considered the most common pattern
of midfoot CN deformity where the skin ulceration occurs medially over the exposed talar
head. The second most common pattern is rotation of the forefoot on the hindfoot with the
weight bearing on the lateral border of the forefoot [62]. Arthrodesis of both the medial and
lateral column has been recommended, as isolated fusion of the medial column has been
associated with higher failure rates with loss of correction and loss of fixation [63, 64].
330 20 Surgical Reconstruction of the Charcot Foot

Complications such as loss of reduction, nonunions/malunions, and implant fixation

failure are more commonly reported in midfoot CN realignment arthrodesis due to the
biomechanical bending loads transmitted through the arch along with poor bone quality,
impaired bone healing and peripheral neuropathy [5, 62–69].
Because of the high complication rates seen in CN midfoot reconstruction, Sammarco
[70] introduced the concept of ‘superconstruct’ fixation methods to improve stability of
arthrodesis, reduce loss of correction and lessen fixation failure. These techniques are
­characterised by: (i) extending the fixation beyond the zone of fusion to joints unaffected
by CN, (ii) resecting sufficient bone to adequately reduce the deformity and reduce soft tis-
sue tension, (iii) using the strongest implant device that can be safely accommodated by the
surrounding soft tissue envelope, (iv) applying the implant device in the position of maxi-
mum mechanical stability. Examples of superconstructs include plantar plating, locking
plates, and axial screw fixation.
Plantar plating technique involves placement of a plating device on the tension surface
of the midfoot fusion. Plantar plating has been shown to be biomechanically superior to
cross screw technique with loads to failure [71]. Despite mechanical superiority, the
­technique is likely less popular due to the wide extensile surgical approach to apply the
plate. Limited series have reported favourable outcomes with successful fusions [17, 72].
Garchar et al. [72] reported a 96% union rate of 25 ft with CN of the tarsometatarsal recon-
struction over a 38 months follow up.
Locking plates are fixed‐angled devices which function as a single beam construct min-
imizing motion between the plate, screw, and bone. The use of locking plate fixation to
the first tarsometatarsal joint has been shown to be superior to traditional screw fixation
techniques [73–75]. One study demonstrated that the position of the locking plate for
medial column fusion whether applied to dorsal or plantar did not differ significantly in
stiffness and cycles to failure [76]. In spite of the mechanical evidence for locking plates
for ­midfoot fusions, the literature for midfoot CN is limited to case study and technique
reports [70, 77, 78].
Axial screw fixation is an intramedullary screw technique passing screws through the
axis of the metatarsals to the tarsal bones spanning the critical area of fusion [79, 80].
Another technique known as ‘beaming’ employs similar principles of intramedullary
axial screw fixation to the medial column but passes a screw between the base of the
third and fourth metatarsals to the tarsal bones to stabilise the lateral column [81]. These
axial screw techniques allow intraosseous rigid beam fixation to bridge the area of
atrophic bone, minimise soft tissue exposure, and provide compression at the site of
arthrodesis (see Figure 20.5a and b). In the cases of a series of 22 patients with axial
screw fixation for midfoot CN followed for an average 52 months, Sammarco et al. [79]
reported 16 unions, 5 partial unions, and 1 nonunion. There were no recurrent disloca-
tions and no loss of limb. All patients were able to return to independent ambulation
within 9.5 months. Grant et al. [81] reported good maintenance of radiographic correc-
tion in 2 groups with an average 31 month follow up: (i) 27 midfoot CN arthrodeses with
medial and lateral column beaming and (ii) 28 midfoot CN arthrodeses with medial and
lateral column beaming and subtalar joint arthroereisis or arthrodesis. A trend for
 20.9 ­Procedures/Outcome Studie 331

(a)

(b)

Figure 20.5 Preoperative radiograph (a) demonstates CN midfoot breakdown with history of
chronic recurrent ulceration submetatarsal 5. Postoperative radiograph (b) demonstrates midfoot
and subtalar joint realignment arthrodesis with restoration of talar–first metatarsal alignment.

improvement of radiographic correction was observed when the subtalar joint was
­stabilised or fused. With the addition of the subtalar joint fusion, the medial and lateral
columns no longer function independently but as one unit to accept load as an aligned
tripod [82]. Richter et al. [64] reported similar findings in a multicentre study of 47
patients using solid midfoot fusion bolts in 27 ft with medial and lateral column with
subtalar joint arthrodesis and six with only medial and lateral column arthrodesis. At a
mean follow up of one year, the study reported an overall 98% union rate but with 12.8%
recurrent ulceration, 6.4% hardware loosening and 4% amputation rate. Failure was more
frequent in cases where only one versus two to three bolts was used and when gastrocne-
mius recession was not performed. Several studies have concluded that isolated medial
column fusion with one intramedullary fusion bolt device was insufficient for midfoot
CN reconstruction due to hardware complications such as loosening or migration and
subsequent nonunion [63, 64, 83].
332 20 Surgical Reconstruction of the Charcot Foot

20.9.2.2 Hindfoot And Ankle

Though an estimated 10% of CN involve the hindfoot and ankle, a systematic review of
1757 procedures over 54 years demonstrated that the hindfoot and ankle comprised 59.9%
(hindfoot 26.1%; ankle 33.8%) of all the surgical procedures in CN reconstruction [4, 19].
The high percentage of procedures performed in this anatomic area suggests that CN
deformities of the hindfoot and ankle are poorly tolerated, and more than half are not
managed well conservatively. Coronal plane deformities of the hindfoot and ankle, such as
varus or valgus deformities, are prone to tissue breakdown due to the prominent malleoli
and thin tissue envelope [84]. Varus or valgus deformities of the hindfoot and ankle also
alter transmission of ground reactive forces from the mechanical axis of weightbearing
from the calcaneus to the femoral head [85]. This misalignment of axial load accentuates
instability of the limb and the shearing forces of the hindfoot and/or ankle deformity,
often causing skin breakdown in the midfoot (i.e. ankle/hindfoot varus causing lateral foot
ulceration) [86].
Realignment arthrodesis of the hindfoot and/or ankle provides a stable limb and
­positions the calcaneus to improve alignment of the mechanical axis of weightbearing of
the limb. If the deformity only involves the hindfoot joints, i.e. subtalar joint, talonavicular
and/or calcaneocuboid joint, a triple realignment arthrodesis would provided adequate
correction.
In longstanding hindfoot and ankle CN deformities, a talectomy may be necessary to
realign the limb. Though shortening of the limb is common after a talectomy, efforts to
maintain the length of the limb is achieved by remodelling and reinserting the talus as
autograft or using bulk femoral allograft [84, 86–89].
Often the talus is involved with hindfoot and ankle CN deformities thereby requiring a
tibiotalocalcaneal arthrodesis to sufficiently reduce and stabilise the limb. Though multiple
methods of fixation have been described, retrograde intramedullary nail has been the
implant device of choice due to biomechanical strength compared to screw and plate fixa-
tion methods, load sharing capacity and minimally invasive application [90–92].
Preservation of the talus or use of bulk femoral allograft in cases where there is avascular
destruction of the talus has been advocated for secure fixation of the retrograde intramed-
ullary nail despite one series reporting a threefold increased likelihood for complication
with use of bulk femoral allograft compared to a group without allograft [86, 89, 93, 94].
A systematic review of tibiotalocalcaneal arthrodesis in 342 patients with CN and DM
reported an overall 79% union rate and a complication rate of 40% [89]. Though a high rate
of complications are seen in this high risk population, an updated systematic review found
that the overall limb salvage rate in 354 patients undergoing tibiotalocalcaneal arthrodesis
for hindfoot and ankle CN was achieved in approximately 90.1% [84].

20.9.2.3 Internal/External Fixation

Whilst there is no consensus regarding the best method of fixation for CN reconstruction,
the decision to use internal versus external fixation is multifactorial and largely based on
surgeon preference. Most authors would agree that internal fixation is contraindicated in
patients with an active infection. Internal fixation is traditionally the fixation method of
choice for one stage acute deformity correction providing static compression though
screws or plates or dynamic compression with plating on the tension side of the fusion
 20.9 ­Procedures/Outcome Studie 333

site. Creating compression at the fusion sites provides stability to minimizing motion to
allow bone healing and is dependent on the quality of fixation purchase into the bone.
Achieving compression in CN reconstruction can be complicated by decreased bone min-
eral density causing regional osteopenia commonly seen with diabetes related CN [95–99].
The use of superconstructs techniques can address these issues of internal fixation in this
compromised bone [70].
In cases of significant bone loss from CN joint destruction, open wound, and/or acute/
chronic osteomyelitis, external fixation is the method of choice. The use of internal fixation
in the presence of open wounds or infections is not recommended, as implant contamina-
tion can become a source of chronic infection. As opposed to internal fixation, external
fixation does not rely on bone quality for stabilization and does not require large extensile
surgical exposures to apply internal plates and screws. The load sharing capacity of exter-
nal fixation device, such as a circular ring fixator can effectively bridge large defects whilst
providing relative stability to the limb. Additionally, dynamic external fixators can be incre-
mentally adjusted to address soft tissue contractures associated with chronic CN deformi-
ties for gradually deformity correction [100].
Outcomes of CN reconstruction comparing internal and external fixation methods have
been evaluated through a systematic review. This review compared 12 studies (totaling 275
procedures in 274 patients) with internal fixation to 11 studies (341 procedures in
319 patients) with external fixation. Dayton et al. [101] estimated an 87.3% success rate
(union, stable pseudoarthrosis, return to ambulation) with internal fixation and 92.9% suc-
cess rate with external fixation. Unsuccessful outcomes (recurrence of deformity, infection,
unsuccessful revision, amputation) were reported in 12.7% cases of internal fixation com-
pared to 7.0% of cases with external fixation. The odds of a successful outcome with exter-
nal fixation was 13.2 whilst the odds of successful outcome with internal fixation was 0.52
times likely compared to the odds of success with external fixation. One notable limitation
of this systematic review was the level 4 evidence of the studies included in the review,
which are subjected to selection bias and nonuniform definitions of terms to define success
and complications.
Comparison between internal and external fixation techniques for midfoot CN recon-
struction has been evaluated through a systematic review. Lee et al. [102] evaluated 11
studies comprised of 88 ft in 85 patients with internal fixation and 38 ft in 38 patients with
external fixation. They reported a 90% relative risk reduction of nonunion and 42% relative
risk reduction of postoperative ulcer formation with internal fixation compared to external
fixation. Additionally, there was a trend for return to functional ambulation when internal
fixation was used. There were outcomes measures that favoured the use of external fixation
for midfoot CN reconstruction. The use of internal fixation increased the risk of periopera-
tive or intraoperative fractures by 50% compared to external fixation. Additionally, patient
with internal fixation had a 1.5 times increase likelihood for LEA, 2 times increase risk for
deep infection, and a 3.4 times increase in wound complications compared to external fixa-
tion. These findings were based on a small number of studies without a uniform scheme to
classify the severity of midfoot deformities that underwent reconstruction.
Although a higher likelihood of successful CN limb salvage has been reported with the
use of external fixation, a higher complication rate has been associated with external
­fixation techniques [47, 101, 103–110]. Use of external fixation in patients with diabetes
334 20 Surgical Reconstruction of the Charcot Foot

experienced a higher rate of surgical site infections of 5.9% compared to 1.5% without dia-
betes and a sevenfold higher risk for wire complications [47, 108]. Another study reported
that 20.8% of patients undergoing single stage reconstruction with static fine‐wire circular
external fixation developed an infection in at least 1 pin tract site [104].

20.9.3 Ancillary Procedures

20.9.3.1 Achilles Tendon Lengthening
The prevalence of equinus contractures (defined as less than 0° of dorsiflexion at the level
of the ankle joint) in patients with diabetes has been estimated between 10.3 and 37.2%
[111, 112] Patient with diabetes with equinus were three times more likely to present with
increased peak plantar pressures than those without equinus [112]. Armstrong and Lavery
[113] reported that peak plantar pressures were significantly higher in the patients with CN
and patients with neuropathic ulceration compared to the pressures in patients without
history of CN and patients with neuropathy without ulceration. Peak pressures were all
located in the forefoot of all groups but highest in patients with CN. Therefore, this signifi-
cant increase in forefoot load is believed to be a predisposing risk factor for the develop-
ment of CN and midfoot breakdown.
Several studies have shown that Achilles tendon lengthening and gastrocnemius reces-
sions can reduce the deforming forces on the neuropathic foot and subsequent CN
related morbidity [113–124]. Hastings et al. [116] demonstrated that lengthening of the
Achilles tendon improved ankle joint dorsiflexion, decreased peak plantar pressure and
improved gait performance measures. Maluf et al. [121] suggested that the decrease in
forefoot peak pressures and time pressure integral following lengthening of the Achilles
tendon were a result of reduced plantar flexor power rather than changes with ankle
dorsiflexion.

20.9.3.2 Post Operative Management

The convalescent period for patients that have undergone CN reconstruction is often pro-
longed due to delayed bone healing in diabetes. The initial postoperative period involves strict
non‐weightbearing with total contact or short leg casting for a minimum of three months
until bone healing is observed. Patients are then transitioned to protected weightbearing in a
cast or a removable boot walker for up to an additional three months until healing of the
fusion sites have been confirmed and postoperative oedema is sufficiently resolved to be
casted for extra‐depth custom shoes with custom inserts or custom brace, such as a Charcot
Restraint Walker. Average time from operative CN reconstruction to therapeutic shoes was
approximately 27 weeks [12, 28, 125]. Patients are educated regarding the need for lifelong
protective shoes or bracing.

20.10 ­Outcomes of Charcot Reconstruction

From 1963 to 2014, a review of 126 reports on CN reconstruction revealed the majority of
studies were evidence level 4 (61.9%) and level 5 (33.3%) with fewer studies at evidence level
3 (3.17%) and level 2 (1.57%) [18, 19]. To date, no prospective, randomised, comparative
 20.11 ­Summary of Evidence Based Recommendation 335

multicentre trials have been published. There are no studies comparing outcomes between
operative to nonoperative treatment nor to primary amputation.
Overall, the outcomes for CN reconstruction are favourable. Systematic review of
the literature of CN reconstruction found that the complete fusion rate was 76.4%,
partial, fibrous or nonunion rate was 22.4% and the amputation rate was 1.2% [18].
Incomplete or nonunion following CN reconstruction was considered successful if the
limb was stable, plantigrade, braceable and ulcer‐free. Shazadeh et al. [126], in their
systematic review of surgical intervention for CN of the midfoot, reported a 91% radio-
graphic fusion rate and 6% amputation rate after surgery. The two most common pro-
cedures reported for CN midfoot fusion was midfoot fusion bolts and multilevel
external fixation.
LEA has been shown to be the greatest fear in patients with diabetic foot disease [8].
This belief likely influences surgeons’ decision to attempt CN reconstruction even in
cases where the probability of salvage is low. Wukich and Pearson [127] evaluate
­primary transtibial amputation in 13 patients with nonreconstructable CN with osteo-
myelitis. They reported statistical improvement on both the self‐reported outcomes on
the Medical Outcome Study Form 36‐item health survey and the Foot and Ankle
Ability Measure with the exception of the mental quality of life, which did not reach
statistical significance. Approximately, 92.3% of patients in the cohort were satisfied
with the amputation and held no reservations. This report demonstrated that elective
amputation can provide a favourable outcome in high‐risk patients with nonrecon-
structable CN.

20.11 ­Summary of Evidence Based Recommendations

●● TIMING – There is limited evidence supporting operative intervention during the acute
phase of CN. Whilst the optimal time for operative intervention is inconclusive, most
surgeons would agree that surgery is not advisable during the acute phase of CN unless
there is severe deformity with pending tissue loss.
●● LOCATION – Over 57.9% of surgical cases for CN are performed for the hindfoot and
ankle joint, which suggest that this anatomic location is less favourably managed with
conservative treatment.
●● EXOSTECTOMY – Removal of bony prominences of the midfoot can relieve areas of
focal pressure causing ulcerative lesions. (Grade C Recommendation)
●● REALIGNMENT ARTHRODESIS – Realignment and arthrodesis can provide stability
and address deformities that are unbraceable and cause recalcitrant ulcerations.
Favourable outcomes are not only inclusive of complete bony unions but stable nonun-
ions as well. (Grade C Recommendation)
●● ACHILLES TENDON LENGTHENING – Lengthening of the Achilles tendon can reduce
forefoot pressures by reducing torque and improving ankle dorsiflexion with weightbear-
ing. (Grade B recommendation)
●● INTERNAL VERSUS EXTERNAL FIXATION – The choice between internal and
external fixation is base on the presence of an ulceration or infection of soft tissue or
bone. In general, the use of internal fixation is not recommended in the presence of
336 20 Surgical Reconstruction of the Charcot Foot

infection. There is evidence that likelihood of a successful outcome following CN

reconstruction favours the use of external fixation despite complication rates; however,
more comparative trials are needed to provide a meaningful recommendation. (Grade I
recommendation)
●● Whilst the level of evidence supporting operative management of CN is growing, there
are no prospective randomised controlled trials comparing operative reconstruction ver-
sus nonoperative care versus amputation to date. The instability, recalcitrant ulceration,
severe deformity, and nonplantigrade foot continue to be the best indications for opera-
tive reconstruction for CN.

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amputations for non‐reconstructable charcot neuroarthropathy in patients with diabetes:
a preliminary report. Diabet. Med. 30 (3): e87–e90. doi: 10.1111/dme.12060.
 345

21

Amputation in the Diabetic Foot

Michael S. Pinzur1 and Adam P. Schiff2
1
Orthopaedic Surgery, Loyola University Health System, Maywood, IL, USA
2
Department of Orthopaedic Surgery, Loyola University Medical Center, Maywood, IL, USA

21.1 ­Introduction

The development of modern battlefield medicine allowed many soldiers to survive World
War II battle injuries. Ernest Burgess used this motivated young and healthy patient popu-
lation to develop the modern functionally oriented approach to amputation surgery.
Burgess viewed the amputation as the first step in rehabilitation. Using a modern evidence‐
based model for healthcare, we need to address the impact that the destructive component
of the injury or disease process makes on the affected individual, and the steps we can take
to return them to, as close as possible, their pre‐injury or disease state. Historically, many
patients with diabetic foot infections were treated definitively with major amputation.
Over the past few decades, dedicated limb salvage programmes and improvement in endo-
vascular surgery have resulted in a reduction in major amputations. The goal of this chap-
ter is to provide the tools for physicians to address the unique needs of diabetic patients
facing both major and minor lower extremity amputation.

21.2 ­Impediments to Rehabilitation in the Diabetic Amputee

The psychological impact of amputation on quality of life has been best studied in trauma
patients. The Lower Extremity Assessment Project (LEAP) was an observational study of
over six hundred civilian patients who sustained mutilating lower extremity injuries, of
which over one hundred fifty underwent amputation. Validated outcomes tools were used
to achieve longitudinal observation of the impact of the injury on their quality of life. One
of the most enlightening insights gained from this pivotal investigation was the apprecia-
tion that ‘family support structure’ was a vital factor for successful rehabilitation following
traumatic amputation [1]. Using knowledge gained from this observational study, the core
investigators used similar tactics to evaluate amputees from ‘Operation Enduring Freedom’.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
346 21 Amputation in the Diabetic Foot

The Military Extremity Trauma / Amputation Limb Salvage Study (METALS) investigation
gave us further insight into these affected individuals, demonstrating that traumatic ampu-
tees had a high probability to exhibit severe symptoms of depression or Post Traumatic
Stress Disorder (PTSD) [2].
The diabetic population additionally brings special cognitive and judgement impair-
ments related to their neuropathy in addition to the aerobic limitations due to their
co‐morbid cardio‐vascular disease, that negatively impacts both on wound healing and
rehabilitation [3]. Unlike young patients with traumatic amputations, patients with
­diabetes typically do not have pain at the residual limb. Quality of life in diabetic patients
after amputation is directly related to the ability to ambulate. Consequently, in patients
with diabetes amputation, surgery should not viewed negatively, but rather as the first
step in rehabilitation. The ability to ambulate after amputation maintains ­cardiovascular
fitness and reduces mortality.

21.3 ­The Lower Extremity as an Organ of Weight Bearing

The normal human foot is composed of 28 bones that allow the dual functions of a shock‐
absorber at heel strike and a stable platform to allow propulsion at push‐off. The ligaments
that connect the bones of the foot are relaxed when the foot is loaded at heel strike. This
unlocked position of the joints, combined with the unique durable cushioned plantar skin
and subcutaneous fibrous connective tissue, allows the foot to dampen the impact of
weight‐bearing. As the foot transitions from the unlocked load acceptance position of ankle
dorsiflexion and foot supination at heel strike to the locked position of ankle plantar flexion
and foot pronation at push off, the foot is able to transition from an organ of dampening
weight acceptance to a stable platform for propulsion at push‐off.
Unlike the adaptable weight‐bearing organ of the normal foot, the residual limb of a
transtibial amputation is generally composed of one or two bones and a soft tissue envelope
that must interface with a prosthesis to mimic the organ functions of the normal foot.
When we surgically create an amputation stump, we need to be cognizant of these dual
functions to create a terminal organ that will interface with a prosthesis to provide pres-
sure‐dissipating cushioning at loading and stability for push‐off [4].

21.4 ­Metabolic Cost of Walking with an Amputation

Our self‐selected walking speed is determined by multiple factors that allow us to optimise
energy consumption during walking. We are most efficient when healthy and well rested,
and least efficient when impacted by illness or injury. Our engineering colleagues view the
joints of our lower extremity as energy couples. Illness or injury to the limb makes the
mechanical construct both less energy efficient and more prone to activity‐related discom-
fort. Prosthetic joints are not as efficient as the ‘original equipment’. The graph in figure
one depicts the metabolic / energy cost of walking with a prosthesis. The more proximal
the level of amputation, the greater is the negative impact on function. Note that the
­transfemoral amputee uses very similar energy consumption during normal walking and
maximum walking speed. Since these studies are performed in the laboratory, this is akin
 21.5 ­Limb Salvage vs Amputation 347

to having to run at all times [5–8]. We have further learned that amputees tend to take a
similar number of steps every day. This metabolic cost impacts on their daily lives making
amputees ration the number of steps they will take [9].

21.5 ­Limb Salvage vs. Amputation

Several important factors should be addressed by the treating surgeon before making the
decision to proceed with limb salvage vs. amputation, regardless of the disease or injury
indication. Experience in trauma has taught us that the best time to make that decision is
at the time of injury. It becomes very difficult to convince a patient to remove a non‐­
functional limb after a substantial effort has been made to take the path of functional limb
salvage. Experience would suggest that many diabetic patients with related foot complica-
tions fear amputation more than death. Patients with poorly conceived reconstruction
plans can be impaired by a poorly functional limb or nerve‐mediated regional pain.
The questions to be addressed when determining limb salvage or amputation, whether
the evaluation is in the emergency department, the diabetic foot clinic or the hospital inpa-
tient unit are:
●● Will limb salvage outperform amputation and prosthetic limb fitting?
The surgeon should have a realistic expectation of the functional outcome following both
limb salvage or amputation.
●● What is a realistic expectation of the clinical outcome following limb salvage or
amputation?
It is unlikely that every patient will achieve the best result that the surgeon has ever
achieved. Most surgeons will achieve a bell‐shaped curve of clinical outcomes for a given
set of clinical parameters, with most patients being in the middle of the curve. When
initiating a treatment plan, the surgeon and the patient should have a realistic expecta-
tion whichever course is taken.
●● What is the cost of limb salvage?
Beyond the financial costs and the resources consumed during limb salvage treatment,
one must consider the other costs to the patient. These include the lost wages from being
out of work, the depletion of financial reserves, time lost from work, and the emotional
costs associated with the multiple necessary surgeries [10].
●● What are the risks?
When establishing a risk assessment for limb salvage vs. amputation, the surgeon should
consider factors beyond a simple determination of surgical‐associated morbidity. One
should also factor the risks of the multiple necessary surgeries and anaesthetics, the
potential for sepsis, the time necessary for rehabilitation, and the potential for narcotic
addiction. When each of these questions are addressed prior to the initiation of treat-
ment, the decision often becomes far more straightforward.
●● Development of a Rehabilitation Amputation Level
Each of these issues should be addressed to determine the most distal functional ampu-
tation level with a reasonable probability of achieving wound healing. The creation of a
durable and healthy amputation stump is essential if prosthetic fitting and functional
ambulation are reasonable goals for the individual patient.
348 21 Amputation in the Diabetic Foot

Once these four questions are addressed, the decision to proceed with limb salvage or
amputation generally becomes patient‐centric.

21.6 ­Amputation Level Selection

In our modern outcomes‐oriented environment, it is clear that retention of limb length is

closely correlated with optimal functional outcomes. When planning amputation surgery,
we should strive to retain as many functional joints and create an amputation stump that is
compatible with the available tissue and the potential for prosthetic limb fitting. The most
difficult decisions arise when we are required to choose between a longer residual limb
length with a poor soft tissue envelope and a more proximal amputation level with a more
optimal residual limb. Results of the LEAP study would suggest that the poor functional
outcomes of the 17 knee disarticulations was due to sub‐optimal amputation stumps as
opposed to poor ability to utilise a prosthesis. When the data was closely scrutinised, it was
determined that most of the knee disarticulations performed in the LEAP study were per-
formed within the zone of injury and had poor soft tissue envelopes. Those patients would
likely have fared better with an optimally performed transfemoral amputation [1]. Despite
the technical ability to achieve limb salvage, maintenance of unstable, non‐plantigrade foot
may result in inferior function compared to a well done lower extremity amputation with
modern prosthetic fitting. The decision on specific amputation level is based on clinical
examination, vascular inflow, and the ability to heal a surgical wound at the most distal
functional amputation level.

21.7 ­The Terminal Organ of Weight Bearing

Load Transfer / Weight Bearing in Lower Extremity Amputation

Our bioengineering colleagues view weight bearing as the transfer of load between the
amputation stump and the prosthetic socket. The ground reaction force vector is applied to
the amputation stump directly in disarticulations at the knee or ankle levels and thorough
total surface bearing in the transosseous transfemoral or transtibial amputation levels. We
use the terms direct load transfer, or end‐bearing in disarticulations, and indirect load
transfer, or total surface bearing in transosseous amputation levels.
End‐bearing disarticulations behave much like normal weight transfer in a sound limb.
Long bones are expanded at the level of the metaphysis to create a larger surface area for
distribution of the weight bearing load, and composed of low elastic modulus cancellous
bone to dissipate the impact of loading. A cushioned end pad acts to substitute for the
dampening and cushioning function of the durable planter tissue of the foot. Since the
actual bony loading is similar to normal, prosthetic socket fit is not crucial. This is a valu-
able feature in patients with significant volume fluctuations, e.g., renal failure, where the
socket can be adjustable to compensate for volume changes (Figure 21.1a and b) [11, 12].
The soft tissue envelope serves as a cushion to dampen the impact of weight bearing. The
bioengineering concept of indirect load transfer is better known in the prosthetic world as
total surface bearing (Figure 21.2a and b). This method of prosthetic socket construction is
 21.7 ­The Terminal Organ of Weight Bearin 349

(a) (b)

Figure 21.1 Direct load transfer in (a) knee disarticulation and (b) ankle disarticulation
amputation levels.

used in transosseous amputation levels where the surface area of the terminal bone is small
and the bone is composed of higher stiffness cortical bone. The theoretic concept is to
unload the small surface are of the stiff cortical bone of the terminal tibia in the transtibial
amputation level and terminal femur in the transfemoral level. By flexing the knee 7 – 10°
in the transtibial prosthesis and adducting the femur in the transfemoral prosthesis, pres-
sure can be taken away from the distal end of the bone and distributed over the entire sur-
face area of the residual limb. To accomplish this task, prosthetic socket fit becomes crucial.
If the patient loses as few as five pounds, they will bottom out and develop either pain or
ulceration overlying the prominent terminal cortical bone. If they gain weight, they will
not be able to get in to the prosthetic socket. The residual bone of transosseous amputees
normally pistons during weight bearing, When the soft tissue envelope of the residual tibia
or femur is composed of mobile muscle and full‐thickness normal skin, the bone will pis-
ton within the soft tissue envelope. When the soft tissue envelope is adherent to the bone,
the pistoning occurs between the skin and the prosthetic socket, creating shear forces that
lead to blisters and skin breakdown. This is best addressed surgically by creating an optimal
soft‐tissue envelope. When the skin of the amputation stump is adherent to the bone, the
prosthetist can attempt to compensate by using some form of a silicone liner as an interface
between adherent skin and the prosthetic socket (Figure 21.3a and b) [13, 14].
350 21 Amputation in the Diabetic Foot

(a) (b)

Figure 21.2 Indirect load transfer in (a) transfemoral and (b) transtibial amputation levels.
Figures 21.1 and 21.2 come from the AAOS Atlas of Amputations.

(a) (b)

Figure 21.3 Creation of a soft tissue envelope.

 21.9 ­Tissue Managemen 351

21.8 ­The Soft Tissue Envelope

The residual bone of an amputation stump serves as the platform for load transfer in lower
extremity amputation. The bony platform of the amputation stump functionally serves as
the surrogate for the 28 bones of the normal foot. The ability to adapt to uneven surfaces
and altered loading forces will need to be accommodated by the prosthetic socket and the
soft tissue envelope, which serves as the surrogate for the durable tissue of the plantar sur-
face of the normal foot. The optimal soft tissue envelope is composed of mobile muscle and
full‐thickness skin (Figure 21.3).
The first step in creating a terminal organ of weight bearing is the removal of all non‐
viable tissue. This process should be completed without consideration of the reconstruc-
tion, as retaining marginal tissue leads to less favourable outcomes. Once all non‐viable
tissue is removed, all viable tissue should be retained to assure retention of as much nor-
mal tissue for reconstruction as possible. When performing amputation for a diabetic foot
infection, the reconstruction is often performed at a second surgical stage to allow the
ascending soft tissue infection associated with infection, gangrene or infected gangrene, to
recover, and ensure infection‐free margins.
When staging amputation surgery for infection, the safest option is open wound manage-
ment with either a vacuum‐assisted wound closure device (VAC) or moist gauze dressings.
If there is redundant viable‐appearing residual tissue, a reasonable alternative wound man-
agement option is provisional loose wound closure without tension. A planned staged return
to surgery allows take‐down of the provisional wound closure, secondary debridement and
formal creation of a durable cushioned soft tissue envelope. The use of skin traction should
be avoided, as the traction adds further insult to the zone of injury or infection.

21.9 ­Tissue Management

Experience, rather than evidence, has provided generally accepted principles in creating
amputation residual limbs. The use of tourniquets has not been effectively studied in
amputation surgery. Accepted practice is to avoid the use of tourniquets in limbs that have
previously undergone vascular surgery or angioplasty (recent or remote as well?
Unknown – I would leave it a bit vague so as to avoid using a tourniquet in any questiona-
ble dysvascular limbs.). When a tourniquet is used, it should be deflated prior to wound
closure to obtain adequate haemostasis. Arteries should be ligated with suture ligatures, i.e.
stick ties, to avoid late bleeding from a simple ligature that is extruded by the pulsations of
the artery. Venous bleeding can be controlled by simple ligature, metal vascular clips, or
electrocautery.
In creating a transosseous residual limb, soft tissue stripping from bone should be limited
to the amount required to create the soft tissue envelope. Excessive periosteal stripping
should be avoided to avoid late prominent periosteal bone formation. Bone necrosis from
thermal burning with power saws can generally be avoided by cooling the bone with cool
saline during the bony transection.
Crushing nerves with clamps should be avoided, even when one plans to resect the
crushed section of nerve. Crush is likely a major factor for the development of phantom‐limb
352 21 Amputation in the Diabetic Foot

or residual limb pain following amputation. The best practice is to gently grasp a nerve with
a gauze sponge, apply gentle traction, and transect proximally with a fresh, sharp scalpel
blade. Whilst every transected nerve will develop a neuroma, a neuroma embedded in mus-
cle is less likely to produce neuropathic pain.
Native full‐thickness skin is far more durable than any coverage obtained with graft-
ing or healing by secondary intention. All viable skin should be retained for use in con-
struction of the eventual functional amputation stump. When full‐thickness skin is not
available, one must consider options of healing by secondary intention with or without
the use of a vacuum‐assisted wound closure device, skin grafting, or plastic surgery soft
tissue transfer.

21.10 ­Outcomes Following Amputation

The rehabilitative process should start prior to surgery in elective amputation, and as soon
as possible following emergency amputation for infection. The amputation surgeon should
use similar methods of pre‐operative planning as fracture or joint replacement surgeons.
Each step of the amputation process should be accomplished with a reasonable surgical
plan. Early transfer training and ambulation with crutches or a walker should be accom-
plished prior to prosthetic limb fitting. Peer counselling has been extremely valuable in
dealing with the inevitable psychological hurdles that follow amputation [3, 9, 15–17]. It
appears that diabetic and dysvascular patients that undergo amputation followed by suc-
cessful prosthetic limb fitting appear to have improved clinical outcomes and quality of life
as compared with those individuals who become confined to a wheelchair [18].

21.11 ­Surgical Amputation Levels

21.11.1 Hallux Amputation

A functional hallux (great toe) is essential for normal walking. In the normal foot, the
flexor hallucis longus creates stability along the medial column of the foot during terminal
stance phase. It is the stability of the medial column of the foot that allows the quadriceps
to extend the knee against a stable foot platform during the push‐off phase of gait [19, 20].
Loss of flexor hallucis longus or brevis function leads to medial column instability and a
relatively apropulsive gait. Adequate functional stability can be achieved by retention of
the proximal metaphysis of the proximal phalanx and the insertion of the flexor hallucis
brevis. The optimal soft tissue envelope is hallux amputation is accomplished with the so‐
called ‘terminal Syme’s amputation’. The nail and involved bone of the distal phalanx are
removed through a dorsal approach. If infection or trauma dictates removal of the terminal
proximal phalanx, care should be taken to preserve the proximal metaphysis with the
attachment of the flexor halluces brevis. The plantar flap can then be loosely re‐attached to
create a stable hallux (Figure 21.4 – Lee figure 1).
Rotational or ‘fish‐mouth’ types of flaps are reasonable second choices. There is no neces-
sity for orthotic modification to footwear following hallux amputation. Patients with
 21.13 ­Ray Resectio 353

(a) (b)

Figure 21.4 (a) Hallux infection. (b and c) Amputation through the proximal phalanx, maintaining
the insertion of the flexor hallucis brevis.

­ erceived weakness or instability at terminal stance phase of gait can use a carbon graphite
p
‘Morton’s extension’ to substitute for absent flexor hallucis longus.

21.12 ­Lesser Toe Amputation

There is little functional loss from lesser toe amputation. The exception is the second toe,
where disarticulation may lead to a severe hallux valgus with prominence of the medial
border of the first metatarsal. For this reason, an attempt should be made to retain the
proximal phalanx metaphysis of the second toe (Figure 21.5 – Lee figure 2). The second
important consideration in lesser toe amputation is maintenance of a non‐prominent
parabola of the forefoot. The local pressure on a retained single prominent toe makes
accommodation difficult within a depth‐inlay shoe (Figure 21.3). These patients often
­benefit from some type of orthotic insole with a ‘toe‐filler’ to prevent the residual foot from
sliding within the shoe.

21.13 ­Ray Resection

Single outer (first or fifth) ray resection is generally used for osteomyelitis of an involved
outer metatarsal. It is rarely indicated in dysvascular disease due to the geographic nature of
the disease process. First ray resection should be avoided, when possible, in active ­individuals,
due to the likelihood of developing an apropulsive gait pattern due to loss of the flexor hal-
lucis tendons. There is a role in older individuals where the loss of propulsion is not as
354 21 Amputation in the Diabetic Foot

(a) (b)

Figure 21.5 (a) Amputation of the second toe increases the risk for the development of a severe
ahllux valgus. (b) Retention of part of the proximal phalanx of the second toe prevents this risk.

noticeable. Fifth ray resection can be well toler-

Figure 21.6 Fifth ray resection.
ated when the base of the metatarsal with the
attachment of the peroneus brevis tendon is
retained. The downside deformity associated
with fifth ray resection is the late development of
a severe varus deformity secondary to muscle
imbalance following disengagement of the per-
oneus brevis. Care should be taken to retain the
base of the fifth metatarsal with the attachment
of the peroneus brevis during fifth ray resection.
Oblique osteotomy of the metatarsal will allow
maintenance of a smooth lateral border of the
residual foot.
Lateral (first or fifth) ray resection is per-
formed with the so‐called ‘tennis racquet’ inci-
sion. Wound management can be accomplished
with primary or delayed primary closure, open
wound management, or loose approximation of
wound edges to allow sufficient drainage during
the perioperative period (Figure 21.6).
Central ray resection is controversial. It can
be an effective method of initial debridement
of infection. Once the infection is resolved
and the patient is medically optimised, trans
­metatarsal or tarsal metatarsal amputation is a
 21.15 ­Hindfoot Amputatio 355

very ­reasonable clinical outcome. The risk of exposure associated with attempting sec-
ondary wound closure or delayed wound healing should be considered before attempting
to complete a central ray resection [21].

21.14 ­Midfoot Amputation

Midfoot amputation can be performed at the transmetatarsal or tarsal–metatarsal levels.

Both levels of amputation provide a reasonable platform for weight bearing, but are rela-
tively apropulsive due to the loss of the lever arm at terminal stance phase of gait. Whilst it
provides a stable platform for weight bearing, the residual foot has a very limited lever arm
for propulsion. The result is a stable foot with limited propulsion. In a younger patient, the
Syme’s ankle disarticulation amputation should be considered, where a dynamic elastic
response prosthetic foot can provide a propulsive gait pattern.
The most durable soft tissue envelope is accomplished with a plantar based flap. This
flap will generally require the bony transection to be performed at the level of the ­proximal
metaphysis of each of the metatarsals. The down side trade‐offs to achieve this improved
lever arm for push‐off is the necessity to use less durable ‘fish‐mouth’ dorsal–plantar
flaps and the risk for late plantar pressure ulcers under the residual metatarsal shafts
(Figure 21.7).
There are trade‐offs that needs to be considered when considering the length of the
bony transection of the metatarsal shafts. Distal metatarsal shaft transection will pro-
vide more walking propulsion, whereas proximal metatarsal shaft transection will
decrease the risk of late recurrent ulceration under the residual metatarsal shafts.
Percutaneous tendon–Achilles lengthening or gastrocnemius lengthening is always
advised in tarsal–metatarsal amputation, and should be considered in trans metatarsal
amputation, as a method of avoiding late equinus deformity which occurs due loss of
the foot dorsiflexors.
Post‐operative management is best accomplished with a short leg walking cast for four
weeks to achieve muscle balance following tendon–Achilles lengthening [19, 20].
Orthotists argue that a ‘prosthetic’ combining a toe filler with ankle foot orthosis makes
this a very functional level. Whilst this is functionally correct, many patients reject using
the complex ‘prosthesis’. Post‐operative management should include a short leg cast to
avoid heal ulcers secondary to over‐lengthening of the Achilles tendon with either tendon
Achilles lengthening or gastrocnemius muscle lengthening [22].

21.15 ­Hindfoot Amputation

Hindfoot amputation is a reasonable option as a method of treating life‐threatening

­infection. It is not a good long‐term functional outcome for several reasons due to the high
likelihood for developing a severe late equinus deformity (Figure 21.8). Even when success-
ful, the residual limb provides no lever arm for walking propulsion. These patients are
functionally far better served with the Syme’s ankle disarticulation, which allows end bear-
ing and space for a dynamic elastic response prosthetic foot.
356 21 Amputation in the Diabetic Foot

(a) (b)

(c)

Figure 21.7 (a–c) Steps for creating a plantar flap for a proximal transmetatarsal amputation.
(b) Weight bearing radiograph. A proximal metaphyseal transmetatarsal amputation level creates a
stable base with a low potential to develop late transfer leasions.

21.16 ­Symes’s Ankle Disarticulation Amputation

The Syme’s ankle disarticulation is an end‐bearing amputation that retains the weight
bearing surface of the distal tibia and the normal soft tissue envelope of the retained heel
pad. The metabolic cost of walking is close to age‐matched controls, and far less than tran-
stibial amputees. Patients require minimal gait training and rarely require hospitalization
in a rehabilitation unit [4, 19, 23, 24].
The surgery is now performed at a single stage. The apices of the fish‐mouth incision
are placed at the anterior mid‐points of the medial and lateral malleoli. The incision is
taken down to the bone, followed by removal of the talus and calcaneus via sharp dis-
section. Care is taken to protect the posterior tibial artery, which is the primary blood
 21.17 ­Transtibial Amputatio 357

(a) (b)

Figure 21.8 (a) A successful hindfoot amputation leaves no lever arm for walking propulsion.
(b) This patient had a resection of 1 cm of Achilles and was immobilised in a cast following
hindfoot amputation. The risk for this development suggests that this level should be avoided.

supply of the flap. The malleoli are removed flush with the articular surface of the
retained tibia and the metaphysical flares of the distal tibia and fibula are removed
with a small power saw. The heel pad is then secured to the retained tibia with a non‐
absorbable suture placed through a drill hole in the anterior corner of the residual tibia
(Figure 21.9) [23].
Weight bearing with a walking cast with rubber heel can be initiated as early as two
weeks if the surgical wound appears secure. Early prosthetic fitting can be accomplished
with a preparatory prosthesis as soon as two weeks following surgery.

21.17 ­Transtibial Amputation

Transtibial amputation is the default amputation level performed when partial foot ampu-
tation is not indicated. The tibial length is best performed at a level of 10–12 cm below the
joint line. This level allows creation of the most durable gastrocnemius soft tissue envelope.
Historical fibular transection is performed 1 cm proximal to the tibia, although fibular tran-
section at essentially the same level creates an excellent bony platform for load transmis-
sion when walking with a prosthesis. The long posterior flap should be equal to the length
of the diameter of the limb at the level of amputation, plus 1 cm. The anterior flap should
be 2 cm to allow creation of the extended posterior flap which will lessen the shearing
forces applied to the limb and surgical scar during early weight bearing. The anterior
­surface of the tibial should be bevelled to accommodate shearing during weight bearing.
358 21 Amputation in the Diabetic Foot

(a) (b)

Figure 21.9 Syme’s ankle disarticulation. (a) Intra-op. (b) At one year.

(a) (b)

Figure 21.10 (a and b) Creating a long posterior flap for transtibial amputation.

The posterior gastrocnemius muscle fascia is attached to the anterior compartment fascia
of the leg and the periosteum of the tibia 1–2 cm proximal to the tibial transection. This
myodesis allows for the creation of a bulky extended posterior flap that will facilitate early
prosthetic fitting. This bulky tissue is valuable during early prosthetic fitting as it dampens
the shearing forces applied to the region of the surgical wound during early prosthetic
­fitting [11, 12, 25] (Figure 21.10).
In reliable patients, a rigid plaster dressing is often used during the preoperative period.,
This rigid dressing prevents knee flexion contractures and facilitates shaping the stump for
 21.19 ­Transfemoral Amputatio 359

prosthetic fitting. Preparatory prosthetic fitting can be initiated as early as two weeks, dic-
tated by the early healing of the surgical wound [16, 17].

21.18 ­Knee Disarticulation Amputation

Knee disarticulation should be the default amputation level in patients with the ability to
heal a wound at the transtibial amputation level, but do not project to be able to walk with
a prosthesis [11, 12, 26, 27]. Those patients who will be able to successfully walk with a
prosthesis can take advantage of the walking stability afforded by end bearing in a pros-
thetic socket and the intrinsically stable polycentric prosthetic knee joint [28]. The long
posterior flap technique is virtually identical to the posterior flap used in transtibial ampu-
tation (Figure 21.11). The patella can be excised or can be used in the flap. The quadriceps
tendon is sutured to the cruciate ligaments to bring soft tissue coverage to the distal aspect
of the femur.
Weight bearing with a temporary prosthesis can be initiated as soon as the surgical
wound is secure due to the end‐bearing nature of the amputation stump.

21.19 ­Transfemoral Amputation

Traditional transfemoral amputation with a traditional anterior–posterior ‘fishmouth’

­incision disengages the adductor muscles and leads to the typically inefficient ‘abductor
lurch’ gait pattern associated with transferal amputation. The long medial adductor myode-
sis flap technique takes advantage of improved blood supply from the obturator artery, and
tends to negate the negative effects of adductor disengagement (Figure 21.12) [29, 30].

(a)

(b)

Figure 21.11 (a and b) Long posterior flap for knee disarticulation.

360 21 Amputation in the Diabetic Foot

(a) (b)

12 cm

Figure 21.12 (a and b) Schematic for adductor myodesis in transfemoral amputation performed
with a medial flap.

21.20 ­Conclusions
Ernest Burgess stresses amputation as CONstructive surgery, i.e. the first step in the reha-
bilitation of a patient with a non‐functional limb. Much as when we perform total joint
arthroplast, we need to think of the surgery in rehabilitation terms. We need to surgically
plan, construct the amputation stump as a terminal organ of weight bearing, and initiate a
carefull conceived rehabilitation programme. With this strategic plan, we can function
much like our reconstructive colleagues and optimise the functional outcomes and quality
of life for patients with non‐reconstructable diabetic foot pathology.

­References

1 Bosse, M.J., MacKenzie, E.J., Kellam, J.F. et al. (2002). An analysis of outcomes of
reconstruction or amputation of leg‐threatening injuries. NEJM 347: 1924–1931.
2 Doukas, W.C., Hayda, R.A., Frisch, M. et al. (2013). The military extremity trauma
amputation / limb salvage (METALS) study. J. Bone Joint Surg. 95: 138–145.
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limb prosthetics. J. Prosthet. Orthot. 6 (supplement): 18.
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24 Finkler, E.S., Marchwiany, D.A., Schiff, A.P., and Pinzur, M.S. (2017). Long term outcomes
following Syme’s amputation. Foot Ankle Int. 38 (7): 732–735.
25 Ficke, J.R. (2016). Transtibial amputation: surgical management. In: Atlas of Amputations
and Limb Deficiencies (eds. J.I. Krajbich, M.S. Pinzur, B.K. Potter and P.M. Stevens),
485–492. American Academy of Orthopaedic Surgeons.
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Stevens), 525–536. American Academy of Orthopaedic Surgeons.
 363

22

Rehabilitation of the Amputee

Karen Kowalske and Merrine Klakeel
University of Texas, Southwestern Medical Center, Dallas, TX, USA

22.1 ­Lower Limb Amputation and Prosthetics

Limb loss is a common condition affecting the American population with approximately
1.7 million people living with limb loss. Rates of amputation from trauma and cancer are
decreasing, but unfortunately, rates of amputation for diabetes and vascular disease
­continue to increase [1, 2] For individuals with diabetes, rates of amputation are highest in
those with retinopathy, coronary artery disease, or Charcot joints [3, 4].
Although amputation surgeries are not the most glamorous or considered challenging, a
thoughtful approach with careful consideration of the impact on function is essential to
maximise outcome [1]. In selected diabetic patients, health related quality of life and func-
tion can improve after major amputation [5].
In general, limb length preservation is the goal in amputation surgery. In patients with
diabetes, understanding the state of the vascular supply is essential to avoid the need for
multiple surgeries. This can cause significant delays in prosthetic fitting which decreases
the probability of prosthetic use [6]. Methods of assessing blood flow such as hair growth,
presence of peripheral pulses, non-invasive arterial testing, and transcutaneous oxygen
tension can be used for good surgical planning. Amputation principles including beveling
of the bone, shortening of the nerves, and an adequate skin closure are essential to assure
a successful functional outcome. Post op dressing can be a standard soft dressing or a rigid
cast dressing. Rigid dressings decrease edema and protect the suture line but have not been
definitively proven to change outcome [7]. Mobility after amputation, particularly with
regard to major amputation, is directly related to quality of life and mortality. Diabetic
patients who are able to ambulate after amputation report higher quality of life and experi-
ence lower mortality rates than patients who are not able to ambulate [5, 8].
Amputation and prosthetic fitting is best understood by evaluating the specific amputa-
tion level and the options available for prosthetic fitting. Center for Medicare and Medicaid
services (CMS) allocates for specific componentry based on the Medicare Functional
Classification Measure (MFCM). This classification, also known as K levels, was developed
in 1995 (Table 22.1). Designed to create uniformity in prosthetic prescription and quantify

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
364 22 Rehabilitation of the Amputee

Table 22.1 K levels.

K-Level Descriptor Foot/Ankle Knee

K0 This patient does not have the ability or Not eligible for Not eligible for
potential to ambulate or transfer safely with or prosthesis prosthesis
without assistance, and a prosthesis does not
enhance his/her quality of life or mobility.
K1 This patient has the ability or potential to use a External keel, SACH Single-axis,
prosthesis for transfers or ambulation on level feet, or single-axis constant
surfaces at fixed cadence – a typical limited or ankle/feet friction knee
unlimited household ambulator.
K2 This patient has the ability or potential for Flexible-keel feet and Single-axis,
ambulation with the ability to traverse low-level multiaxial ankle/feet constant
environmental barriers such as curbs, stairs, or friction knee
uneven surfaces – a typical community
ambulator.
K3 This patient has the ability or potential for Flex-foot and flex-walk Fluid and
ambulation with variable cadence – a typical systems, energy-storing pneumatic
community ambulator with the ability to feet, multi-axial ankle/ control knees
traverse most environmental barriers and may feet, or dynamic
have vocational, therapeutic, or exercise activity response feet
that demands prosthetic use beyond simple
locomotion.
K4 This patient has the ability or potential for Any ankle foot system Any ankle-
prosthetic ambulation that exceeds basic appropriate knee system
ambulation skills, exhibiting high impact, stress, appropriate
or energy levels – typical of the prosthetic
demands of the child, active adult, or athlete.

Abbreviation: SACH, solid ankle, cushion heel.

the potential benefit of ambulating with a prosthesis, this measure was not based on any
form of scientific research [9]. Other factors such as prior mobility, balance [10], other
medical co-morbidities, and psychological factors play a significant role in determining
overall functional outcomes and prosthetic use. Incorporating other outcome measures
such as the Amputee Mobility Predictor (AMP) [11] or the Prosthetic limb user’s survey of
mobility (PLUS-M) which is a validated patient self-report [12] can be useful for supporting
a specific prosthetic prescription. Further discussion of specific prosthetic prescription will
be reviewed as we discuss amputation level.

22.2 ­Foot Amputations

The foot is comprised of numerous small bones with finite movements through the joints,
allowing for a smooth roll as the individual moves from heel strike to toe off during the
stance phase of the gait cycle. There are multiple pressure points in the foot that are more
susceptible to diabetic foot ulcers, such as toes and plantar metatarsal heads [13].
The ­decision on the site of amputation is determined after weighing the need to maintain
 22.3 ­Foot Orthotic 365

maximum walking ability versus prompt healing after surgery [14]. Multiple biomechani-
cal variables negatively influence the gait cycle after a partial foot amputation that include
decreased normal dynamic dorsiflexion range, inverted foot positioning on initial contact,
irregular rollover with decreased push off, and decreased plantar flexion power generation
from shortened foot as well as the smaller base of support. The residual limb carries
increased plantar pressure due to decreased weight bearing surface area after amputation.
Foot orthotics can be combined with an ankle foot orthoses (AFO) to transfer the
weight bearing pressure over larger surface area to above the ankle whilst reducing shear
forces [15].
Partial foot amputations include toe amputations, ray amputations, transmetatarsal
amputations (TMAs), trasometatarsal disarticulation aka Lisfranc amputation and the
transtarsal disarticulation (aka Chopart amputations). Orthotic devices used for partial foot
amputations include insoles, toe fillers, slipper sockets, ankle foot orthoses (AFOs), and
clamshell sockets [16]. These devices are designed to fill the shoe and redistribute pressure
from the intact skin and amputation site [16]. Fragile or very short residual limbs will need
more proximal unloading with a traditional AFO or a clamshell type brace that supports
the foot whilst limiting ankle motion [16].

22.3 ­Foot Orthotics

Foot orthotics are fabricated by a similar process regardless of whether the prosthesis is
being fitted for a hallux amputation, a ray resection, TMA, Chopart or Lisfranc amputation.
Once the amputation site has healed, the prosthetist obtains a negative mould using foam,
plaster, or fibreglass., The negative mould is filled with plaster to create a positive model
used to fabricate the prosthesis with Plastazote lined with polyurethane foam or EVA and
cork composites [15]. Similarly, computer-aided design and computer-aided manufactur-
ing (CAD-CAM) system can mill the cork composites from computer scan of the residual
limb and later cover with a layer of EVA or plastazote to create the custom prosthesis [15].
Ray amputations result in loss of structural foot lever [15, 17]. Hallux amputation results
in increased energy consumption and decreased force generated during the toe off, result-
ing in change in gait mechanics and pressure distribution in the foot [18]. The loss of first
and second ray results in the highest loss of lever arm for toe-off propulsion. A carbon fibre
foot plate can be incorporated into the partial foot prosthesis or steel shank built into the
shoe to lengthen the lever arm [15].
Depending on the level of partial foot amputation, slipper type elastomer orthosis can be
fabricated to match the patient’s skin tone, and shape of the opposite limb [19]. The ­orthosis
should be custom fitted to equally distribute pressure throughout the foot, with the bottom
of the arch being more pressure tolerant. Although many patients like this concept, it is
almost never covered by insurance. In general, most are fitted with toe fillers to occupy
additional space within the shoes minimizing movement of the foot inside the shoes to
prevent shear injury [15].
TMA generally has good successful outcome as long as the tibialis anterior muscle
remains attached to base of first metatarsal. Custom moulded foot orthosis provide even
pressure distribution and carbon fibre or steel shank used as a lever arm for push off.
366 22 Rehabilitation of the Amputee

Rocker bottom shoes provide an additional roll over to assist with toe off whilst minimizing
pressure over the TMA amputation site but may create instability for those with balance
impairment [15]. If the tibialis anterior muscle is not functional, the foot tends to plantar
flex with resulting skin breakdown at the distal stump end. In this case stabilizing the ankle
with an AFO is required.

22.3.1 Proximal Foot Amputations

Proximal foot amputations are rarely successful for individuals with diabetes. Trans tarsal
amputation (Lisfranc), tarsal dislocation (Chopart) and Symes (ankle disarticulation) are
prone to develop an equinus deformity secondary to unopposed gastrocnemius and soleus
function. These amputations are predisposed to significant difficulty with wound healing
as a result of perfusion and nutrition [20].
Proximal foot amputations generally require an AFO style prosthesis attached to the
foot plate to adequately offload the pressure generated during the late stance of the gait
cycle. The pressure is re-distributed to the lower leg through the AFO held in place using
Velcro or belts. Use of foot orthotics has been shown to provide improved function long
term [17, 21]. The foot plate prosthesis that can fit into a shoe is generally less bulky in size
and weight. This allows for the use of residual function in the ankle and hind foot, despite
the greater force being applied to the stump, subjecting it to further complications in the
future [17].

22.4 ­Transtibial Amputations

Below knee amputations (BKA) are attempted in patients with severe peripheral arterial
disease (PAD), non-reconstructable Charcot deformities and patients with refractory soft
tissue and bone infections. Similar to partial foot and proximal foot amputations, BKA
disrupts the normal gait mechanics and requires higher energy costs for ambulation. The
low cost, standard prostheses can provide satisfactory gait for low speed ambulation, but is
insufficient for high speed gait, inclines and varying surface levels. The ankle is a multi-
axial joint that provides proprioceptive feedback and adjusts the angle for varying surface
levels whilst providing the additional energy for propulsion during plantar flexion and toe
off [22].
During the amputation, the tibia and fibula are cut shorter than the muscle flap and
shaved down prior to covering the bone with muscle flap to provide a weight bearing
surface. The amputation is classified as short, standard, or long BKA based on length of
the stump. A long BKA stump retains 50% or greater of the extremity length, whilst
standard BKA retains 20–50% of the tibial length and short BKA only has 25% or less of
the tibial length [23, 24]. Although, preserving length is ideal in other types of amputa-
tion, this not true for transtibial amputation. Length greater than 30% makes prosthetic
fitting difficult due to insufficient space for all necessary components and the preflexion
required for ideal socket fitting without causing leg length discrepancy. The compo-
nents necessary for a below knee prosthesis include socket, suspension, shank, ankle
joint, and foot.
 22.4 ­Transtibial Amputation 367

22.4.1 Transtibial Sockets

Sockets are in direct contact with residual limb and serves as the extension of the body to
hold the distal components of the prosthesis, whilst also adequately distributing the pres-
sure placed on the residual limb from weight bearing and ambulation. The availability of
new materials such as urethanes, mineral-based liners, and silicones have led to the crea-
tion of dynamic sockets that are uniquely contoured to the residual limb with the memory
capacity that adapts to the changing shape of the residual limb during the gait cycle with
muscle activity [25].
The socket is designed with small degree of preflexion to increase the weight bearing
surface and promote smoother gait initiation [26]. This also helps prevent hyperextension
of the knee on heel strike. Adjustments to the prosthetic feet can be made to either dorsi-
flexion or plantarflexion to further stabilise the knee [27]. A small amount of a knee flexion
contracture post operatively can be accommodated when fabricating the socket, however it
is important to educate the amputee to maintain limb in full extension to prevent contrac-
tures during the post-surgical care.
The residual limb in BKA has certain pressure tolerant areas and pressure sensitive areas
to which special care much be provided to prevent pressure ulcers. Pressure tolerant areas
include patellar tendon, pretibial muscles, popliteal fossa (gastroc-soleus muscles), lateral
shaft of fibula and medial tibial flare. The pressure sensitive areas include: tibial crest, tibial
tubercle, tibial condyles, fibular head, distal tibia and fibula, hamstring tendons, and
patella [28].
The patellar tendon bearing socket has total contact with the residual limb but focuses
the majority of the pressure associated with weight bearing through the pressure tolerant
areas of the residual limb. The anterior wall extends over a small portion of the patella
anteriorly, allowing the individual to weight bear through the patellar ligament [25].
The total contact socket allows for total surface contact with the residual limb, provid-
ing an even distribution of weight throughout the entire residual limb. The total contact
also provides increased sensory feedback allowing for better control of the prosthesis
[25]. The major difference between total contact socket and the patellar tendon-bearing
socket is the lack of pressure relief through the pressure sensitive area as seen in the
patellar tendon bearing sockets. Total contact socket is used in combination with sleeve
suspension, which also provides a longitudinal tension holding the socket and prosthesis
in place [28].
Supracondylar/suprapatellar socket is preferred for short residual limbs. The supracon-
dylar/suprapatellar socket extends over the patella and femoral condyles and wraps around
the couture of the knee. This allows for better knee stability, added suspension and larger
surface area for weight bearing especially in a short residual limb [25]. This design allows
for easier kneeling, and does not limit hyperextension; therefore candidates must have a
stable cruciate ligaments of the knee [28].
A suction socket utilises a silicone liner over the residual limb. Suction is achieved with
a one-way valve on the distal aspect of the socket that allows air to escape as the individual
dons the socket and pushes the residual limb into the custom fit socket [25]. Although don-
ning and doffing of a suction socket is more difficult, this design diminishes displacement
of the stump inside socket, decreasing gait asymmetry and pain at distal stump site [29].
368 22 Rehabilitation of the Amputee

22.4.2 Suspension
Suspension hold the prosthesis onto the residual limb [30]. There are multiple types of
suspensions available in the market, some of which are detailed below. The suspensions
can be used in combination if needed for tighter hold [30].
Pin Suspension uses a pin at the distal end of a gel or silicone liner that is inserted into
the socket and locked in place. The pin is unlocked by using a button to release the lock
when doffing the prosthesis. This suspension provides reassurance that the prosthesis is in
place and is often used with the first fitting.
Suction suspension uses a gel or silicone liner over the residual limb. The weight of the
individual is then used to push the residual limb and liner into the socket as air is pushed
out through a one-way valve. A lanyard attached to the liner can also be used to manually
pull the limb into the socket [25]. This suspension provides improved proprioceptive feed-
back and is the ideal design for those who are very physically active.
Vacuum suspension uses a mechanical pump to remove the air between the sleeve and
socket creating a vacuum that provides a tight suspension. Vacuum or suction system
employ a seal-in liner or cushion liner and sleeve that decrease pain at the distal end of the
residual limb [31].
Sleeve suspension uses an elastic sleeve over the socket and the distal portion of the
thigh. The sleeve is donned by rolling the sleeve up the distal thigh, once the residual
limb has been adequately positioned in the socket. The sleeve seals off the top of the
socket preventing air from entering, allowing for a tight fit during ambulation [25].
The sleeves are available in silicone, neoprene, latex and polyurethane; are inexpensive
and easy and effective to use [25]. The silicon or polyurethane sleeves tend to retain
heat and cause perspiration [25]. Amputees with excessive soft tissue surrounding the
popliteal fossa have difficulty donning the sleeve due to increased creasing on knee
flexion [32, 33].
Cuff Suspension uses a cuff to hold the prosthesis tightly in place. The strap wraps
around the distal thigh at a level just proximal to the femoral epicondyles. Cuff suspension
is ideal for standard BKA with good knee stability [28].

22.4.3 Shank
The shank provides the appropriate height for the prosthesis and transfers weight between
the socket and the prosthetic foot [30]. Shanks are available as exoskeleton and endoskele-
ton. Exoskeleton shanks are made of wood or polyurethane and are laminated with rigid
plastic on the outside and filled with lightweight filler [34]. They are more durable and is
ideal for heavy-duty use or for children. Exoskeleton shanks/socket combination are harder
to modify. The endoskeleton systems are made of lightweight durable material such us
carbon fibre, titanium, steel, aluminium or graphite pylons. The pylon is adjusted for the
height of the prosthesis and additional features for a smoother gait can attached to the
pylon like a shock absorber and torque absorption (simulates transverse plane rotation use-
ful for golfers) [30]. This flexibility facilitates a smoother gait. The individuals have the
option of covering the pylon with a lightweight softer material that is more cosmetically
appealing [34].
 22.5 ­Ankle/Foot Component 369

22.5 ­Ankle/Foot Components

There are multiple options for the ankle-foot prosthesis in the market, allowing for person-
alised shopping experience specific to the needs of the amputee [35]. The basic foot pro-
vides high level of stability for an older, debilitated amputee whilst a dynamic foot allows
for greater motion within the ankle and foot, proving a smoother gait on different surfaces.
Some ankles can be pre-programmed, to adjust for the stride length and speed [22] whilst
the newer microprocessor ankles provide variable resistance in response to the level of
pressure applied to the prosthesis from the walking surface and the angle of the shank in
relation to the gait cycle [22]. This system provides a smoother gait, closer to the normal
gait cycle and is energy conserving for the amputee.
The solid ankle cushioned heel (SACH) is the earliest type of prosthetic foot and remains
the most commonly used due to its stability, durability and low cost. SACH is composed of
a cushioned heel to mimic ankle plantar flexion and rigid keel [35]. SACH has a fixed ankle
that provides stability, making it a good option for a K-1 ambulator.
The Single-Axis Foot allows for plantarflexion and limited dorsiflexion during ambulation.
This foot has two bumpers that allow plantarflexion and dorsiflexion along the sagittal plane,
and the bumpers can be adjusted to vary the level of ankle sagittal motion [35]. This type of
foot is also traditionally used for K1 ambulators. Plantarflexion provides stability as the ground
reactive force (GRF) moves from posterior to the knee on heel strike to anterior to the knee
with plantarflexion during the stance phase. The plantarflexion movement of the single axis
foot and shift in GRF helps the amputee to walk down ramps without the knees bucking.
In order to try to recreate the significant power that the ankle generates in a small range
of motion [35] there was a desire to move towards lighter weight and more energy efficient
feet. This lead to the commercial use of carbon fibre and fibreglass to create a more energy
efficient prosthesis under new category of prosthesis called Energy-storing-and-returning
feet (ESR) or Dynamic response feet. The ESR foot stores energy on heel strike as the weight
of the person compresses the carbon fibre and provides a push forward during toe off, as
the material decompresses. The keel has a spring like capacity and requires a strong enough
heel strike to activate the technology and is not ideal for low-level users. ESR feet are ideal
for K2 and higher-level ambulators [35].
The Flex Foot, made commercially available in 1987, was a new design made with 100%
carbon fibre shank and heel spring, allowing the entire prosthesis to flex, store and return
energy. Springlite foot is a one-piece design that contains both carbon fibre and fibreglass
filaments surrounded by a soft cover [35]. Currently, there are many sophisticated designs
available to meet the cosmetic and functional needs of the amputee. Some high profile feet
incorporate the pylon and keel as one flexible large single piece, as seen used by amputee
athletes. These are specific for the sport and used interchangeably for the purposes of the
sport by the K4 ambulator.

22.5.1 Knee Disarticulation Amputations

In general, every effort should be made to preserve the knee due the significant increase in
energy consumption for an amputation through or above the knee. The knee disarticula-
tion level is essentially a soft tissue operation associated with shorter surgical times and
370 22 Rehabilitation of the Amputee

minimal blood loss. Unfortunately, it is somewhat problematic to manage from a prosthetic

perspective. Even the narrowest of knee components will cause a cosmetic deformity with
a prominence of the femoral component in sitting, and a foot that does not touch the
ground. In general, this level of amputation is accommodated in a polycentric knee, which
is a very stable system but is not cadence responsive. Microprocessor knees are too bulky to
be accommodated for through knee amputation. Knee disarticulations, rather than a tran-
stibial amputation, is a reasonable alternative in non-ambulatory diabetic patients.

22.5.2 Transfemoral Amputation

There are two different surgical approaches for transfemoral amputation. Myoplasty of the
quadriceps, and anchoring the adductors to the lateral femur which stabilises the femur
and recreates the adduction lever arm. This provides padding of the distal femur and puts
the femur in slight adduction for maximizing gluteus medius function (abductor) and
improved stabilization in stance. Additionally, anchoring the quadriceps and hamstrings
to opposing sides of the femur provides for additional femoral stabilization [1]. The fitting
generally becomes more difficult with amputation at higher levels, and often results
in characteristic symptoms of local pain, skin ulceration and discomfort [2, 13, 14]. In
­addition, patients with a short femoral stump, skin grafts, scarring or heterotopic bone
formation may be entirely unable to use a socket prostheses, or choose not to use them due
to the problems associated with socket fitting. A survey of 97 patients with transfemoral
amputations in Sweden reported a very high prevalence of problems related to the use of
socket prostheses, including: 72% with symptomatic sweating of the stump, 62% with sores
or skin irritation from the socket, 61% with interference to mobility and 51% with pain in
the stump when standing or walking [2]. In addition, these patients consistently reported
a significantly diminished quality of life when compared with able-bodied participants.
Prosthetic fitting requires a transfemoral socket, suspension, knee unit, and ankle foot
unit. The fitting of the ankle and foot are no different than for those with transtibial
amputation.

22.5.3 Socket and Suspension

In the past, transfemoral amputations were fit with a quadrilateral socket. This socket has
a self for the ischium to sit on with compression anteriorly in an attempt to keep the
ischium in place. This prosthesis often requires a silesian band or waist belt for suspension.
The more modern design is called an ischial containment socket or narrow medial lateral.
As in the name, the ischium is incorporated within the socket. The socket is narrow in the
medial lateral direction. The medial aspect is lower to accommodate the adductor tendons.
The femur is positioned in slight flexion and adduction in an attempt to maximise the mus-
cle efficiency of gluteus medius and maximus. This socket can be fit with a very stable pin
locking system similar to that used for transtibial amputations. For those with ideal length,
low body fat, and good balance a suction suspension is possible. Both of these sockets have
been shown to hinder the range of motion of the involved hip, which contributes further to
difficulties in ambulation [15]. These sockets are also very uncomfortable to sit in and are
very hard to fit on those with obesity or a short residual limb. The problems associated with
 22.5 ­Ankle/Foot Component 371

socket prostheses have remained largely unsolved, despite extensive and continuing search
into socket design and manufacturing [17]. Consequently, at least one-third of all amputees
still experience symptomatic socket–residuum interface problems, leading to reduced pros-
thetic use and markedly reduced quality of life [13, 36]. Energy consumption at this level
of amputation is also very high with a range of 65–100%, and many diabetic patients do not
have the cardiac reserve to ambulate with a transfemoral amputation.

22.5.4 Knee Units

There has been a significant advance in the technology available for knee units. Unfortunately,
these units add weight and are quite expensive. The most basic knee unit is a single axis. This
light weight hinge allows for flexion and extension and a manual locking feature. This is
often used as the first knee joint for the frail or elderly. Initially gait training begins with the
knee locked for maximum safety. The knee can be unlocked manually for sitting.
Weight-activated knees, constant friction is used to supply high stability during stance
phase. Transferring the body weight to the knee shall activate an embedded brake that
prevents buckling. This brake is released once the knee is unloaded. However, constant
friction is still present during the swing phase and these results are inefficient during gait
due to the lack of cadence responsiveness. An element that is capable of storing energy,
such as a spring may assist the knee during the swing phase in which it is loaded during
weight bearing and released during the swing phase itself [37].
The polycentric or four bar knee has a changing centre of rotation with movement,
which more closely simulates the anatomic axis of the knee. There is relative shortening in
the swing phase which improves foot clearance [38]. Pneumatic knee units use air pressure
dynamics to adjust the rate of swing. They weigh less than hydraulic knees but provide less
precise cadence control. Hydraulic knee units are cadence responsive via a change in fric-
tional resistance based on the force of compression. This responsiveness is excellent for
young or active individuals but comes at the price or increased maintenance and weight
and higher cost.
Microprocessor knees incorporate an onboard microprocessor with motorised hydraulic
and pneumatic components [39]. It provides increased stability at heel strike and a more
natural movement through stance phase. Gait speed is also increased and most can walk on
uneven surfaces [40]. Weight distribution from sit to stand is also improved [41]. It is run
off a lithium ion battery, which is problematic if the electricity goes out. Due to the expense
of these systems, funding agencies often restrict payment for all but the most advanced
users. This is actually unfortunate as many studies have shown overproportional benefits
for those with the lowest mobility scores [42]. Age, mobility status and aetiology of ampu-
tation are not predictive of an individuals’ likelihood to benefit from a microprocessor knee
[43]. Microprocessor knees also improve activities of daily living in those at a K2 level and
allow step over step on stairs [44].
There is a recent wave of interest in the osseointegrated reconstruction for lower limb
amputees. The initially proposed two stage procedure delayed mobility significantly. Very
recent studies suggest a single stage procedure may be an option. Unfortunately, there con-
tinue to be issues of infection with up to 20% rate of osteomyelitis with 9% requiring
removal [45].
372 22 Rehabilitation of the Amputee

22.6 ­Conclusion

Long-term complications of diabetes such as neuropathy and vascular disease often result
in non-healing wounds, osteomyelitis, or gangrene necessitating amputation. The level of
amputation should be determined based on the underlying blood supply and the functional
options for the individual. If the blood supply proximal to the mid foot is compromised,
proceeding directly to a transtibial amputation may facilitate early prosthetic fitting and
advancing of functional mobility. Energy consumption of most with a transtibial amputa-
tion is not significantly above that of natural walking (approximately 20–25%) and fitting is
possible for almost all. Although prosthetic fitting is possible for transfemoral amputations
and knee disarticulations, the prognosis for successful prosthetic use in patients with dia-
betes is much lower. Therefore, approaching the diabetic patient with a multidisciplinary
team, that includes the surgeon, PM&R physician, therapist, and prosthetist, can help iden-
tify the best amputation site for the patient and help set the expectations and momentum
for successful outcome using prosthesis.

R
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 375

23

Surgery for the Diabetic Foot

Prophylactic and Osteomyelitis Surgery – Is there an Evidence Base?
Javier Aragón-Sánchez
Surgery and Diabetic Foot Unit Department, La Paloma Hospital, Las Palmas de Gran Canaria, Spain

Surgery is becoming an important part of the treatment of foot problems in people with
diabetes. Historically, the only surgical treatment associated with diabetic foot disease
was thought to be some form of foot amputation. Amputations were always performed
when medical treatment failed. However, modern surgeons have been able to provide
new evidence supporting the role of surgery for treating acute problems without amputa-
tion. When surgeons operate on a patient they should prioritise limb salvage but should
also consider the biomechanical consequences of surgery. Clinicians involved in diabetic
foot care should understand that maintaining the patient in remission is sometimes more
difficult than saving the limb in the acute phase [1]. Obtaining a long relapse-free period
is another goal of surgery. Based on this knowledge, diabetic foot surgery has been clas-
sified into four types. Class 1, or elective surgery, include procedures performed on
patients with protective sensation intact to eliminate pain or to improve function; Class
2, or prophylactic surgery, involves the procedures performed on patients with protective
sensation absent, but no open wound to reduce deformity and occurrence/recurrence;
Class 3, or curative surgery, covers the procedures performed on patients with an open
wound with the goal of promoting healing and reducing risk for recurrence; and Class 4,
or emergency surgery, covers the procedures performed with the goal of limiting the
spread of limb- or life-threatening infection [2]. Class 1 surgery is really any foot surgery
performed in people in whom diabetes has not lead to foot-related complications (periph-
eral neuropathy, peripheral arterial disease, or both) and this is not the subject of this
chapter. We will address the role of surgery with prophylactic purposes and for removing
infection in cases of osteomyelitis. One of the advantages of using surgery to treat dia-
betic foot osteomyelitis (DFO) is that bone deformities can be corrected, thus affording
prophylactic, as well as anti-infective, value.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
376 23 Surgery for the Diabetic Foot

23.1 ­The Role of Surgery Preventing Occurrence

and Recurrence of Foot Ulcers

This type of surgery could also be named ‘surgical offloading’. These procedures should be
carried out in the presence of deformities and biomechanical disturbances which will lead
to a foot ulcer and can be surgically corrected. Surgical offloading belongs to the surgical
Classes 2 and 3. In some cases, providing appropriate offloading to heal a foot ulcer is not
possible due to severe deformity; surgery has both curative and prophylactic purposes. The
aim of this type of surgery is to reduce risk for ulceration/amputation, to reduce foot
deformity by providing a stable and painless foot for ambulation and, finally, improving
appearance of the foot [3]. Whilst the assumption of the role of prophylactic surgery for
preventing complications is generally accepted, prospective series and controlled trials
with long-term follow-up are lacking. In a recent review dealing with the recurrence of
diabetic foot ulcers, foot surgery was reported as the intervention with the highest effect of
reducing foot ulcers recurrence [4]. The mean of effect of surgery reported on this review
was 61.8 ranging from 10.4 to 100. It contrasts with a mean effect of 54.3 of self-manage-
ment, 47.2 of therapeutic footwear or 30.9 of integrated foot care. Thus, prophylactic and
curative surgery might reduce re-ulcerations as a part of a comprehensive care of ­secondary
prevention. Combining surgical offloading with postoperative care based on customised
insoles and therapeutic footwear could provide the best approach to these high-risk
patients. However, well-designed studies with long term follow-up are needed in this field.
Despite its potential for reducing recurrences, surgically correcting structural deformity or
improving range of motion is controversial in this high-risk patient population [5]. The
thought was that this type of surgery should be avoided due to a high risk of complications
[6] and it likely remains in non-specialised departments. Armstrong et al. [7] performed a
retrospective case/control study to determine the safety of prophylactic surgery. Thirty-one
patients, 17 of them with neuropathy and foot deformity and 14 with demonstrated pathol-
ogy (history of ulceration, amputation, or Charcot disease) underwent arthroplasties of the
lesser toes. The control group consisted of 33 patients without diabetes who underwent the
same type of surgery. Patients with a history of previous ulceration were significantly more
likely to suffer a postoperative infection (14.3%) than neuropathic diabetic patients with no
history of ulceration (0%) and non-diabetic subjects (0%) (p = 0.04, CI = 3.1–8.6). No dif-
ferences regarding wound dehiscence was found between the groups [7]. No lower extrem-
ity amputations were performed in this series of studies. Although this study was
retrospective, it provides important knowledge about the safety of forefoot prophylactic
surgery compared with the same procedures in non-diabetic patients.

23.2 ­Preoperative Care

Patients scheduled for surgical offloading should carefully be evaluated regarding systemic
(malnourishment, ischaemic heart disease, and renal failure) and local features to prevent
postoperative complications. The assessment of peripheral neuropathy, peripheral arterial
disease and infection are crucial. Patient compliance, tobacco use, mobility and social fac-
tors should be considered when selecting potential surgical candidates [8]. Diabetes-related
 23.3 ­Hallux and First Metatarsal Head Procedure 377

complications (peripheral neuropathy, Charcot neuroarthropathy), smoking and length of

surgical procedure, have been related to surgical site infection after foot surgery more than
diabetes itself [9]. Perioperative glycaemia values 200 mg/dl were associated with
increased rates of surgical site infection after foot and ankle surgery [10]. The optimal level
of glycated haemoglobin, which could be a predictor of surgical morbidity in patients with
diabetes undergoing foot surgery, is unknown. One common problem of the available stud-
ies is that they include patients undergoing emergency surgery. Postoperative complica-
tions could be due to the infectious problem which lead to requiring surgery instead of
glycaemic control. Perioperative glycaemic control during admission was a predictive fac-
tor of amputation in a prospective cohort of 81 patients with diabetes who underwent sur-
gical treatment for osteomyelitis. Glycaemic control before admission, as determined by
glycosylated haemoglobin, did not have any influence on the outcomes [11]. Even though
data from studies are scarce, medical optimization and normalization of glycaemic control
should always be attempted because it has the potential to decrease the risk of postopera-
tive complications. Levels of preoperative glycaemia 200 mg/dl should prevent elective
procedures until glycaemic values have been improved.
Uncorrected severe limb ischaemia is a critical factor precluding foot surgery because of
complications. A recent series from the Netherlands reported 129 cases of limb-sparing
surgery in which healing was achieved in 52% of the cases, 56% underwent reoperations
and 30% of the patients underwent a major amputation [12]. The authors stated that not all
patients underwent vascular assessment, and, in half of the patients, there was a delay in
undergoing revascularisation. Outcomes of diabetic foot surgery are successful when
ischaemia is adequately addressed [13]. After successful revascularisation, a group per-
formed different types of surgery in ulcerated patients. They performed resection of the
involved bone through plantar approach with excision of the ulcer and primary closure,
pan metatarsal head resections (MHR), metatarsal osteotomies, and fifth MHRs through a
dorsal approach. Healing was achieved in 83% of the cases with 7% of reulcerations noted
during the follow-up [13].
Surgical offloading will require an appropriate evaluation of foot deformities, biome-
chanical disturbances and x-ray alterations to plan the surgical approach. The goal is to
increase the range of motion leading to a reduction of the pressure points and then reduc-
ing the recurrence rates. Surgical techniques will depend on the location of the ulcer and
the underlying biomechanical defect.

23.3 ­Hallux and First Metatarsal Head Procedures

Ulcers involving hallux or the first metatarsophalangeal joint (MPJ) are a serious problem
because its amputation is associated with significant biomechanical disturbances. In a ret-
rospective study of 90 patients undergoing amputation of the big toe, 60% underwent a
second amputation, and 17% of these ultimately had a below-the-knee amputation [14].
Ulcers on the big toe can be located at different sites and associated with different biome-
chanical abnormalities [15]. These ulcers may be associated with limited range of motion
of the MPJ, increasing pressure on the hallux during ambulation. Flexion deformity of the
interphalangeal joint (IPJ), IPJ sesamoid bone or abnormal biomechanics of the first ray
378 23 Surgery for the Diabetic Foot

result from excessive pronation and are also frequent disturbances seen in these patients [3,
16]. Although the ulceration may heal with a conservative approach using appropriate off-
loading, the biomechanical abnormalities still exist and recurrence may occur.
Arthroplasties of the IPJ and MPJ are reported in different retrospective series to increase
the range of motion of both joints then decrease pressure under the hallux. Rosenblum
et al. [17] analysed the use of IPJ arthroplasty to prevent big toe amputation. They per-
formed 45 procedures on 39 patients. Thirty-six feet (80%) healed without complications,
five feet (11%) presented complications (four were complicated by wound infection) and
four feet (9%) were deemed failures. No hallux amputation was required in any patient.
Ultimately, 41 of 45 ft (91%) healed without recurrence during 23.6 months of follow-up
(range 4–44 months). Another more recent retrospective study analysed the outcomes of 13
patients undergoing IPJ arthroplasty versus 13 patients who were treated with standard
care [18]. The decision to temporarily stabilise the hallux IPJ was chosen in an individual-
ised way but was not used in cases of infection. The outcomes were favourable to the surgi-
cal group in terms of time to healing (3.5 weeks in surgical group versus 9 weeks in standard
group, p = 0.033) and recurrences (7.7% in surgical group versus 53.8% in standard group,
p = 0.031). No amputations were performed in the surgical group whilst 38.4% were carried
out in standard group, but it did not reach statistical significance (p = 0.06). There were
three postoperative complications. Incisional wound dehiscence in two patients (15.4%)
and infection in one patient (7.7%). Transfer ulcer appeared in two occasions (15.4%) and
they were located at the plantar aspect of the second toe and second MPJ [18]. A patient
who had previously undergone a second ray resection developed a plantar ulcer under the
IPJ of the hallux. The ulcer was resistant to conservative treatment and finally reached the
cortical bone (Figure 23.1). IPJ arthroplasty through a dorsal approach was performed
(Figure 23.2) and no recurrence was found after five years of follow-up.
An audit of Keller arthroplasty showed that this procedure was frequently used in
patients with diabetes having peripheral neuropathy and other medical conditions such as
coronary artery disease and peripheral vascular disease. Regarding foot problems, Keller
arthroplasty was used in cases of ulceration and osteomyelitis as well [19]. Dannels dem-
onstrated that increasing the motion in the hallux led to healing of ulcers in all cases with-
out recurrences during a follow-up of 28.8 months [20]. Furthermore, another group of
authors analysed the outcomes of treating plantar medial IPJ neuropathic ulcers resistant
to offloading with total contact cast (TCC) [21]. They used Keller MPJ arthroplasty with
insertion of a 0.0625 in. Kirschner wire in a group of 14 patients extracted from a group of
78 patients with an ulcer of the plantar aspect of the great toe. These 14 patients displayed
preoperative diminished range of motion of the first MPJ and their ulcers did not respond
to a mean of 40 days of TCC. This surgical group was compared to a similar population of
15 patients without restricted MTP motion and were successfully treated by TCC only.
Sixty-four percent of the surgical group healed within 14 days of surgery, with the remain-
ing ulcers healed within 23 days. Patients treated with TCC only healed after 47 days.
Neither infectious nor hardware-related postoperative complications were reported. The
MTPJ range of motion increased to a mean of 32.1° after Keller arthroplasty [21]. Armstrong
et al. performed a case–control comparing Keller arthroplasty versus standard non-surgical
care [22]. Patients who underwent surgery healed faster and had fewer recurrent ulcers
(standard 35.0% versus surgery 4.8%, p = 0.02) during the six-month follow-up. Armstrong
 23.3 ­Hallux and First Metatarsal Head Procedure 379

Figure 23.1 Neuropathic ulcer under the IPJ of the hallux resistant to offloading and conservative
care.

Figure 23.2 Left: Dorsal incision to approach the IPJ of the hallux. Right: Postoperative x-ray
showing the arthroplasty.
380 23 Surgery for the Diabetic Foot

et al. [22] reported 40% of postoperative infections, which is higher than the 30.7% reported
in a short retrospective series [23] or the absence of postoperative infections in the Lin’s
series [21]. However, 38.1% of the patients belonging to the standard non-surgical group
also had infections (p = 0.9). No differences were found regarding amputation rates (stand-
ard 10.0% versus surgery 4.8%, p = 0.5) [22]. A group of authors, based on their results in a
small retrospective series, recommended performing Keller arthroplasty in patients with
resistant plantar hallux ulcerations, even in the absence of hallux rigidus [24]. Twenty-one
percent of postoperative dehiscence/wound infections and 17% of reulcerations were
reported in this series in which the surgeons did not use a pin [24]. Transfer pressure trans-
fers lesions to lesser toes and is a possible complication of this surgery. Specifically, transfer
lesions after Keller arthroplasty can cause complications of this surgery. Although these
complications did not appear in one series [21], transfer ulcers are common. Recurrence to
the second toe were reported in 3.5% [24] and other authors reported 38.4% of transfer
lesions to metatarsal heads in a small series consisting of 13 ft. These transfer ulcers
occurred at the plantar aspect of either the first, second, third, or fifth metatarsal heads
[23]. Only one patient from the surgical group of the Armstrong’s series had recurrence
located in the plantar heel [22]. Sesamoidectomy could also be a useful procedure for treat-
ing neuropathic foot ulcers located under the first metatarsal head [25]. The authors per-
formed a retrospective study including 26 cases with open ulcerations in which tibial
sesamoid (13 occasions, one bilateral) or both (13 occasions, one bilateral) was carried out.
Four of 26 cases (15.4%) developed reulcerations during a mean follow-up of two years and
nine months [25]. Excision of the tibial sesamoid may predispose to the development of
hallux valgus deformity and excision of both sesamoid bones to the hallux hammer toe.
This was not found during the follow-up in this particular series [25].

23.4 ­Lesser Toes

Toe deformities in patients with diabetes associated with toe ulcers are very common.
Different series have reported good results addressing this problem by means of flexor digi-
torum longus tenotomies for treating distal tip ulcers in a flexible hammer toe. The pub-
lished series includes some patients with ulcers in which the surgery is curative but with a
prophylactic aim as well, and other times, patients without ulcers just for a prophylactic
purpose. Two systematic reviews of this topic have recently been published [26, 27]. The
authors reviewed six retrospective studies with a total of 264 flexor tenotomies performed
on toes with ulcers and 57 performed as a prophylactic procedure in the latest systematic
review [27]. The procedure was also used in ulcers complicated by osteomyelitis. The
­healing rate ranged from 92 to 100% with a low rate of postoperative complications.
Recurrences were found in 12 to 15% of the cases [28–30]. Transfer lesions in an adjacent
toe were found in 8.7% of the cases in a series consisting of 103 tenotomies in which no
recurrences of the same ulcer were found [31]. In the systematic review, patients compli-
cated by osteomyelitis had longer healing periods. All the studies were retrospective but it
could be concluded that flexor tenotomies of the lesser toes is a safe and useful procedure
for preventing and treating diabetes-related toe ulcers. In cases of rigid deformities,
­arthroplasty could be necessary. The long-term outcomes after arthroplasties of the lesser
 23.5 ­Lesser Metatarsal Head 381

toes at a site of previous ulceration were uniformly good, with 96.3% of patients remaining
ulcer-free at a mean of three years postoperatively [7]. A group of authors reported good
outcomes with modified arthroplasties but it was carried out in cases with complications
and will be discussed further [32]. Well-designed studies dealing with lesser toes arthro-
plasties with prophylactic purpose are necessary.

23.5 ­Lesser Metatarsal Heads

Metatarsal osteotomy should be considered for chronic cases of ulcers that are not compli-
cated by osteomyelitis below a specific metatarsal head. Osteotomies have been used for
treating neuropathic plantar ulcers in few series [33–36]. However, few studies have
addressed such a procedure exclusively with prophylactic purpose and without open ulcer-
ation. One series reported a worrying figure of postoperative complications. Sixty-eight
percent of the patients who underwent a closing wedge metaphyseal osteotomy made at
the base of the metatarsal approximately 1 cm distal to the tarso-metatarsal joint with inter-
nal fixation had complications. Although the patients did not have any recurrence, 32%
became complicated by postoperative Charcot disease, 14% had a deep infection and 9%
had transfer lesions [34]. The authors stated that the procedure was associated with a high
rate of complications, as would be expected in this patient population [34]. However,
­previous experiences from other groups did not show such a high rate of postoperative
complications. Rosenblum et al. [13] reported on 39 patients with 42 neuropathic plantar
ulcers complicated by severe ischaemia. After successful revascularization, 15 ft (36%) with
superficial ulcers were treated by an elevating osteotomy at the anatomical neck of the
metatarsal bone through a dorsal approach without using internal fixation [13]. Although
the osteotomy group was not analysed separately, no severe complications were reported in
the series [13]. Tillo et al. [33] reported a retrospective series of 49 patients that underwent
four different types of osteotomies: osteoclasis, v-osteotomy, shortening colectomy and
oblique-sliding osteotomy [33]. Postoperative complications were not reported. Twenty-
seven patients (55%) had neither evidence of reulceration nor transfer lesions. Thirty
patients (59%) developed transfer ulcerations within an average of 17 months and by
19 months three patients (14%) had a recurrence of their original ulcer. Six patients (27%)
had transfer calluses [33]. Recently, two series reported osteotomies in diabetic foot ulcers
performed by percutaneous procedure, also called minimal invasive surgery (MIS). A group
of authors reported a retrospective series of 20 osteotomies performed on 17 patients. Two
patients (11.7%) developed a transfer lesion 4 and 10 months after the procedure and the
osteotomy failed to offload the metatarsal head in three cases (15% of the osteotomies) [35].
A group of authors performed percutaneous extra-articular lesser metatarsal neck osteot-
omy in a prospective cohort of patients who had not responded to non-operative treatment
during at least a six-month period [36]. The series consisted of 35 chronic plantar ulcers
that were treated with 32 operations. Additional surgical procedures (flexor and extensor
tenotomies, osteotomies of the proximal phalanx and osteotomies for hallux valgux deform-
ity) were performed in 26 of 32 operations. The mean healing time was 7.9 weeks (SD 4)
and no recurrences were found after a mean follow-up of 25.3 months [36]. Unlike previous
reports dealing with osteotomies in diabetic foot ulcers, the authors included 60% of ulcers
382 23 Surgery for the Diabetic Foot

that penetrated to the bone or joint (Grade III, University of Texas Wound Classification)
and 68.57% of ulcers with infection (Stages B and D, University of Texas Wound
Classification). However, patients with active infection were excluded and the data
extracted from the classification is not consistent with the exclusion criteria. Despite
including this high rate of deep infected ulcers, only one patient had a postoperative
­infection [36].
MHR [13, 37–43] has been reported for treating neuropathic plantar ulcers. Postoperative
plantar pressures are reduced after MHR thus leading to ulcer healing [37]. No studies have
been reported presenting the outcomes of MHR as a prophylactic method because all stud-
ies were carried out with ulcerated patients. Some of the studies were aimed at comparing
conservative versus surgical approach. Piaggesi et al. [43] included in a randomised trial
with at least 60% of the patients undergoing MHR for treatment of neuropathic plantar
ulcers. Patients who underwent surgical treatment had a higher healing rate, healed faster,
and presented fewer infectious complications and less recurrences. Recurrences occurred
in the same site of previous ulceration in the group of standard care (41%), whilst all the
recurrences in the surgical group (14%) occurred in different sites than that of surgery after
a follow-up of six months. Transfer pressure and reulcerations in other sites are common
after MHR. The first metatarsal showed the highest risk for reulceration (hazard ratio
3.307; 1.472–7.430) whilst the fifth metatarsal showed the lowest risk (hazard ratio 0.339;
0.138–0.832) in one study dealing with transfer lesions. Forty-one percent of reulcerations
were found after 13.1 months of follow-up [41]. The fifth MHR could be the procedure least
associated with reulcerations. Armstrong et al. [39] reported the efficacy of the fifth MHR
versus a group in which standard non-surgical treatment was implemented for treating
neuropathic ulcers. Twenty-seven percent of recurrences were found in the non-surgical
group compared to 4.5% in the surgical group. An example of fifth MHR can be seen in
Figure 23.3. The patient had a neuropathic plantar ulcer under the fifth metatarsal head
which frequently recurred despite using customized insoles. Fifth MHR was performed
through a lateral approach (Figure 23.3). Postoperative x-ray is shown in Figure 23.4. No
recurrence was found after four years of follow-up.

Figure 23.3 Left. Neuropathic plantar ulcer under the fifth metatarsal head. Right: Intraoperative
view of the removal of the fifth metatarsal head.
 23.6 ­Tendon Achilles Lengthenin 383

Figure 23.4 Post-operative x-ray after fifth metatarsal head resection.

Pan MHRs could be a useful procedure in cases of multiple recurrent neuropathic

non-infected forefoot ulcers without ischaemia. This procedure was evaluated in a
case–control retrospective study including 46 patients who underwent pan MHR and
46 patients non-surgically treated who were the control [44]. Patients that underwent
surgery had fewer recurrent ulcers (39.1% for the non-surgical group versus 15.2% for
the surgical group; p = 0.02). There was no significant difference in the incidence of
amputation at any level (13.0% for the non-surgical group versus 6.5% for the surgical
group; p = 0.5) [44].

23.6 ­Tendon Achilles Lengthening

Perhaps the best quality study regarding surgical offloading was carried out by Mueller
et al. [45]. The authors conducted a randomised-controlled trial (RCT) comparing ten-
don Achilles lengthening (TAL) in combination with a TCC for six weeks, versus a TCC
384 23 Surgery for the Diabetic Foot

alone. The authors performed this study to assess the healing rates of forefoot ulcers.
They used a percutaneous procedure by means of three partial hemisections of the ten-
don, placing the foot in 10° of dorsiflexion. Wounds were not closed. Surgery combined
with TCC achieved a 100% success rate in ulcer healing, whilst those treated with a TCC
alone achieved 88% ulcer healing. The recurrence rate was significantly different at two
years of follow-up: 81% recurrence in the TCC group compared with only 38% in the
TAL cohort (p = 0.002). The risk for ulcer recurrence was 75% less at seven months and
52% less at two years than that in the TCC alone group. However, 13% of the patients in
the TAL group developed heel ulcers after treatment [45]. This complication is concern-
ing and has been reported in as high rate as 35% [46] and 47% [47] of patients after
undergoing TAL procedure. Heel ulcers can occur from calcaneal gait associated with
either an overly lengthened tendon or a tendon rupture [48]. Other authors have also
reported the usefulness of TAL or gastrocnemius resection to reduce the rate of ulcer
recurrences when comparing with TCC alone [48]. A recent meta-analysis [49] that
included two RCTs [45, 50] was performed. No statistically significant difference was
reported between TAL or gastrocnemius recession and TCC regarding the time to heal-
ing of diabetic foot ulcers and the rate of healed ulcers. The rate of ulcer recurrence was
significantly lower following TAL or gastrocnemius recession than TCC [49]. In theory,
gastrocnemius recession may lessen the potential complication of iatrogenic heel ulcers.
Surgeons should examine the preoperative calcaneal pitch as demonstrated on lateral
standing radiographs prior to performing Achilles tendon lengthening. In those patients
with a normal calcaneal pitch, caution should be exercised in performing TAL and a
gastrocnemius recession may be an alternative.
In conclusion, available studies regarding surgical offloading are retrospective with
evident selection bias. IPJ and MPJ arthroplasties may be considered effective proce-
dures for preventing neuropathic hallux ulceration without significant ischaemia. This
could lead to reduced recurrences of these ulcers that are associated with high pressure
on the plantar aspect of the hallux. These procedures sometimes have a significant rate
of postoperative infectious complications, wound dehiscence and recurrences due to
transfer pressure. Sesamoidectomy may be a valuable procedure in cases of plantar
ulcerations under the first metatarsal head. Flexor tenotomies of the lesser toes is a
safe and useful procedure for preventing and treating diabetes-related toe ulcers with
flexible deformity. In cases of rigid deformities, arthroplasty could be necessary. In
superficial, non-complicated neuropathic ulcers, osteotomy at the neck of the metatar-
sal without internal fixation through a classical or MIS approach could be a safe proce-
dure but further well-designed research is needed. MHR is a good method to achieve
healing in patients with complicated neuropathic plantar ulcers including metatarsal
head osteomyelitis, however its association with pressure transfer and reulcerations in
other sites limits its role as a prophylactic procedure. Pan MHR may be a useful proce-
dure to prevent recurrences in cases of multiple forefoot ulcers. TAL should be consid-
ered an effective strategy to reduce recurrence of neuropathic ulceration of the plantar
aspect of the forefoot in patients with diabetes mellitus and limited ankle dorsiflexion,
although it could be complicated by new heel ulcers. Well-designed studies with long
term follow-up are needed to definitively establish the role of surgical offloading in
patients with diabetes.
 23.7 ­Curative Surgery for Treating Diabetic Foot Osteomyeliti 385

23.7 ­Curative Surgery for Treating Diabetic Foot

Osteomyelitis

Although amputations remain a common procedure, modern surgeons involved in multidis-

ciplinary diabetic foot teams have developed more conservative surgical strategies to treat
DFO. Conservative surgery is defined as any procedure in which only the infected bone and
non-viable soft tissue are removed, but no amputation of any part of the foot is undertaken
[40]. Different types of conservative surgery for treating DFO has been described (Table 23.1).
Conservative surgery was successful in almost half of the patients admitted for DFO in a series
consisting of 185 surgically treated patients [40]. The author defined the failure of conservative
surgery as the need to perform any amputation of the foot in two settings: [1] impossibility to
perform a conservative procedure during initial operation; or [2] the need to perform any
amputation later than an initially conservative surgical procedure. The risks of failure included
exposed bone, the presence of ischaemia, and necrotising soft tissue infection [40]. In theory,
a conservative surgical approach would change the foot biomechanics less than amputation,
thereby minimizing the risk of reulceration. However, biomechanics of the foot may change
even when small pieces of bone are removed, potentially leading to recurrences [51]. A pro-
spective cohort of patients undergoing surgery for DFO addressed the problems of recurrence
of infection and reulceration. The percentage of recurrence of the infection, reulceration, and
new episodes of osteomyelitis was 4.6, 43, and 16.9%, respectively, in patients with a median
length of follow-up of 101.8 weeks. This study demonstrated that conservative surgery, fol-
lowed by antibiotics guided by bone cultures, is a safe approach to obtain remission of bone

Table 23.1 Types of conservative surgery on diabetic foot osteomyelitis.

Conservative surgery

Ostectomy (also called
‘bone debridement’)
Exostectomy
Distal phalangectomy
Arthroplasty of
interphalangeal joint
Metatarsal head resection
Metatarsal resection
Resection arthroplasty of
metatarsal-phalangeal joint
Sesamoidectomy
Partial calcanectomy
Any removal of bone tissue without formal anatomic limits.
It is frequently carried out through the ulcer. Sometimes is
performed in outpatient facilities to take bone samples for
microbiological purposes.
Totally or partial removal of exostosis. It is frequently carried
out in cases of plantar deformities associated with chronic
Charcot foot.
Removal of any part (or all) distal phalanx. Sometimes is
associated with tenotomies to correct toe deformities
reducing the risk of recurrences
Removal of any interphalangeal joint
Removal of a metatarsal head
Removal of any part of metatarsal bone excluding head
Removal of metatarsal-phalangeal joint. Keller arthroplasty
of the first metatarsal-phalangeal joint is frequently used
Removal of one or both sesamoid bones
Partial removal of the calcaneus
386 23 Surgery for the Diabetic Foot

infection. Reulceration was common and associated with plantar ulcers and Charcot deform-
ity [51]. A randomised trial compared primary antibiotic treatment (90 days) with conservative
surgery (plus 10 days of antibiotics) [52]. No differences were found regarding healing rates
(which was considered as ‘remission’), healing time, and complications requiring subsequent
surgery. Four patients from the antibiotic arm of the study (16.6%) underwent surgery after
worsening. Three patients who were initially treated by conservative surgery underwent a
subsequent minor amputation. No difference in minor amputations was found between the
two groups (p = 0.336). Two reulcerations were detected in the antibiotic group (9.5%), and
four (21%) in the surgical group during the 12 weeks of follow-up after healing (p = 0.670). No
recurrences were found in either groups during follow-up [52]. This study clarified some previ-
ous questions, however the small sample size and short-term follow-up limits the conclusions
that can be drawn and applied in clinical practice [53]. Although, it could be concluded that in
mild and moderate cases of neuropathic non-ischaemic forefoot ulcers complicated by osteo-
myelitis, antibiotic treatment is as effective as surgery.
Recent works highlighted patients with bone margins affected by infection after under-
going amputation for osteomyelitis showed poor prognosis. Residual osteomyelitis at the
pathologic margin was associated with a higher rate of treatment failure, despite the longer
duration of antibiotic therapy [54]. Another retrospective observational study involving 27
patients with diabetes showed that the overall rate of residual osteomyelitis was 40.7%
(11/27). Nine out of eleven patients (81.8%) with positive margins had poor outcomes,
including three re-amputations, three wound dehiscences, one reulceration, one death,
and one chronic wound that required skin grafting [55].

23.8 ­Surgery of Forefoot Osteomyelitis

Phalanxes and metatarsal heads are the most frequent location of osteomyelitis in the feet
of patients with diabetes [40, 51, 56–58]. The most common amputations classically used to
remove infected bone in diabetic patients with forefoot osteomyelitis are toe, ray, and trans-
metatarsal resections [59]. Forefoot osteomyelitis was treated by means of 88% minor and
12% major amputations in a series published in 1994 [60]. Surgery without amputation
may be good for a patient with diabetes because it is aesthetically acceptable [61] although
the impact of this type of surgery on the quality of life has not been addressed.
Removing the distal phalanx can be successfully performed to treat osteomyelitis of
the distal phalanx of lesser toes. The procedure can be combined with flexor tenotomy as
can be seen in Figure 23.5. In cases of involvement of the IPJ, a resection arthroplasty
can be performed [32, 40, 62, 63]. A group of authors described a modified resection
arthroplasty to treat osteomyelitis of the IPJs of lesser toes. After extensive debridement
of bone and soft tissues, they copiously irrigated the wound and inserted a Kirschner
wire, 1.2 mm in ­diameter. Healing was achieved in 25.6 ± 6.2 days with this method and
just three cases of toe amputation were eventually performed [32]. MHR is a very useful
procedure employed by different study groups in cases with osteomyelitis [13, 38–40, 43,
51, 61, 64] however transfer ulcers are very common, especially if the first metatarsal
head is removed [41]. Transfer ulcer to the third metatarsal head after removing the sec-
ond metatarsal head can be seen in Figure 23.6. Osteomyelitis involving the hallux is a
 23.8 ­Surgery of Forefoot Osteomyeliti 387

Distal osteomyelitic phalanx removal

Flexor tenotomy

Figure 23.5 Intra-operative view of a patient who underwent resection of the distal infected
phalanx and flexor tenotomy.

Figure 23.6 Transfer ulcer to the third metatarsal head after removing the second metatarsal
head complicated by osteomyelitis.

serious problem because the hallux has an important role in the biomechanics of the
foot, and the hallux should be preserved if possible. One-stage resection and pin stabili-
sation were reported in a ­retrospective series consisting of 15 patients (18 ft) with an
average follow-up of 48.8 months [65]. Only one patient required a transmetatarsal
amputation after the procedure for ­worsening infection and wound complications.
388 23 Surgery for the Diabetic Foot

Another option is to use external fixation after removing the infected bone [66].
The authors used staged surgical procedures ­consisting of ulcer excision, removal of all
necrotic soft tissue and bone, followed by pulse lavage irrigation, culturing, and polym-
ethylmethacrylate antibiotic cement placement. Subsequently, a mini-external fixator
was placed in four of six cases at the index procedure to stabilise the affected joint. When
the infection was cleared, they used an allogenic bone graft, iliac crest bone graft, or
arthroplasty without bone grafting with the external fixator. None of the surviving sub-
jects developed recurrent ulceration or required amputation after 14 months of follow-up
[66]. Another group reported a cohort including 28 patients with osteomyelitis of the
first ray treated by a technique requiring a one-stage surgical approach [67]. After surgi-
cal debridement with removal of the infected bone, the authors placed antibiotic-loaded
bone cement and stabilised the treated area with an external fixator. Four patients
­developed a relapse of the ulceration after the procedure. During the follow-up period,
no ulceration recurrences, transfer ulcerations, shoe fit problems, or gait abnormalities
were detected in the other 24 patients [67]. Using antibiotic-impregnated cement spacer
to fill the cavity resulting from the removal of the infected bone is another option. The
authors describing this therapy treated seven of 20 patients that presented with osteomy-
elitis of the first MPJ. Bone debridement and antibiotic-impregnated cement spacer were
used in every patient and Kirschner wire was used in three patients. Five patients
required further surgeries including cement removal and metatarsophalangeal arthrode-
sis [62]. The outcomes in this subgroup of patients were good and one of these patients
required a below-the-knee amputation due to complications arising from a new ulcer
under the fifth metatarsal head.

23.9 ­Surgery of Midfoot Osteomyelitis

A large series, including patients with diabetes and mid- and rear foot osteomyelitis, has
not been reported in the medical literature. Most reports that include these patients are
case-reports and it is very difficult to extract conclusions. Cases involving midfoot osteomy-
elitis are frequently associated with underlying Charcot deformity. It has been suggested
that repeat bone resection followed by antibiotic cement spacer or beads in such cases is a
successful method to achieve healing [68]. As a consequence of bone resection, the foot
becomes destabilised and immobilisation has to be enforced. Several ways of immobilising
an unstable foot have been reported, including internal fixation, external fixation or both.
Internal fixation is contraindicated in an area of active osteomyelitis [68]. Circular fixation
based on Ilizarov principles provides stabilisation following correction of deformities, and
can be used in patients with active infections [69].

23.10 ­Surgery of Rear Foot Osteomyelitis

Subtotal and total calcanectomy has been suggested as an option to achieve limb salvage
in patients, including those with diabetes [70–75]. A systematic review of partial or total
­calcanectomy as an alternative to below-the-knee amputation was recently reported [76].
   ­Reference 389

The combined data represented 100 patients that had undergone 76 partial and 28 total
calcanectomies, giving a total of 104 calcanectomies. Forty-nine of 76 partial calcanecto-
mies (64.4%) did not have complications. Total calcanectomy was carried out without
complications in 14 of 28 cases (50%). Seven cases of partial calcanectomy (9.2%) and
four cases of total calcanectomy (14.3%) subsequently required a major amputation
(14.3%). Patients with diabetes had a fivefold greater risk of undergoing a major amputa-
tion [76]. Seventy-five percent of patients maintained their preoperative ambulatory sta-
tus postoperatively, following either partial or total calcanectomy [76]. Once the wound
is healed, the patient will need regular follow-up care, customised insoles and adequate
footwear to minimise the risk of reulceration. Because the Achilles tendon is sacrificed
with partial and total calcanectomy, some type of ankle foot orthosis will be necessary.
Orthotic devices such as an AFO or Charcot restraint orthotic walker (CROW) will be
necessary for patients to maintain their ambulatory status after total or partial calcanec-
tomy [76].
In conclusion, two prospective studies have demonstrated that conservative surgery
without amputation provides an effective approach to remove bone infection from the feet
of patients with diabetes. However, solely retrospective and small series have evaluated dif-
ferent surgical techniques. Although these techniques could be more acceptable to the
patients because they produce minor aesthetic changes on the appearance of the foot, they
are also associated with reulcerations due to pressure transfer. More research is needed to
define the role of surgical treatment of DFO.

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 395

24

Footwear and Orthoses for People with Diabetes

J.S. Ulbrecht1,2 and S.A. Bus3
1
Department of BioBehavioral Health and Medicine, Pennsylvania State University, University Park, PA, USA
2
Mount Nittany Health, State College, PA, USA
3
Department of Rehabilitation Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

24.1 ­Introduction

It is now well established that important foot injuries in diabetic patients are primarily a
consequence of loss of sensation in the feet due to neuropathy, where loss of protective
sensation (LOPS) is defined as that degree of sensory loss at which mechanical injury is no
longer prevented by pain; LOPS is best diagnosed using the 10 g monofilament [1, 2]. Such
lesions can then become ‘non-healing’ because of persistent trauma to the wound ­permitted
by lack of pain [3].
Broadly speaking two types of injuries can occur. The first is stepping on an object or
injuring the side or dorsum of the foot against an object such as furniture, door frame,
small stone in the shoe, etc. And the second is injury due to repetitive trauma associated
with ambulation, where the load associated with each step is sub threshold to cause injury,
but tissue breakdown occurs after many steps. These lesions are typically either plantar
lesions that develop at sites of high plantar pressure or skin breakdown associated with
non-plantar rubbing by a shoe.
It is therefore intuitively obvious that shoes, if they do not fit or function properly, can
cause foot injury in a person with LOPS, but, importantly, that shoes that appropriately
prevent or mitigate exposure of the foot to mechanical forces can prevent foot injury. In this
chapter we will discuss how to approach the prescription of shoes for patients living with
diabetes.

24.2 ­What is a Therapeutic Shoe for a Person Living

with Diabetes?

It is important to remember that just because a shoe is ‘special’, ‘prescription’, ‘diabetic’, or

‘therapeutic’, and perhaps expensive, does not make it right for a specific patient.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
396 24 Footwear and Orthoses for People with Diabetes

24.2.1 The Shoe Upper

Whilst the shoe upper is clearly critical in preventing a significant proportion of foot
injuries in patients with LOPS, we are aware of no published studies that have system-
atically examined how to provide the best shoe upper. Thus, most of the following
is based on opinion developed from other opinion papers in the literature and
experience.
The shoe upper must first and foremost accommodate the foot. Poor footwear fit is
widely believed to cause many foot injuries, ulcers, and even amputations in persons with
diabetes [1, 4]. To prevent injury from simple mis-sizing, it is essential that patients with
LOPS have shoe length and width carefully determined by measurement, since such
patients often cannot give adequate feedback regarding shoe fit. Two studies have demon-
strated that patients with LOPS choose shoes that are at least a size too small in 75–80%
of cases [5, 6].
Thus, professional care is typically needed to provide a shoe upper that accommodates a
foot, even without deformities. Unfortunately, many fashionable shoes fail even in that
regard. Furthermore, many patients with LOPS are older and have specific foot deformities
such as bunions and clawed and hammered toes. Various strategies for accommodating
even significant deformities are available including shoe uppers made of soft material,
shoe uppers made of leather that can be stretched, and ultimately shoe uppers that are
custom moulded (US)/bespoke (UK) specifically for the patient. Simply avoiding shoes
with stitching at key areas of the upper can often make all the difference in avoiding non-
plantar foot injury.
In addition, shoes must also accommodate orthoses that are deemed appropriate for that
patient. As will be discussed later, patients at very high risk of plantar foot injury often
require orthoses of significant thickness. Thus, an extra depth shoe is often needed just to
accommodate an appropriate orthosis.
The last important role of the shoe upper is to protect the foot from the environment.
This is the main reason for recommending primarily closed shoes rather than sandals. It is
more difficult for a small pebble to work its way into a closed shoe than for the same thing
to occur when a person is wearing a sandal. Injuries of the foot by stubbing a toe ambulat-
ing to the bathroom barefoot at night are common, and a shoe upper provides at least some
degree of protection from this type of injury.

24.2.2 Slip-On, Laces or Velcro?

There again is no experimental evidence to guide the provider on this point. However,
lace up shoes are typically recommended to assure a snug closure of the throat of the
shoe. Shoes that are not held on snuggly allow sliding and this could result in distal foot
injury and also permits misalignment of the foot with respect to the orthosis in the shoe.
Some ‘give’ in the lacing can accommodate at least some variation in foot volume due to
edema. Velcro closure is sometimes necessary if the patient cannot tie his or her shoes.
Patients in that case should be taught to close the Velcro as tightly as possible. Slip on
shoes do not provide adequate tightness of the closure nor adequate accommodation of
volume change.
 24.2 ­What is a Therapeutic Shoe for a Person Living with Diabetes 397

24.2.3 Orthoses
The terms ‘insole’ and ‘foot orthosis’ are often used interchangeably, although an orthosis
usually implies that some custom attempt to impact the function of the foot has been
implemented. Orthoses for patients with LOPS should usually be ‘accommodative’ rather
than ‘corrective’. The ‘corrective’ or ‘functional’ foot orthoses that are used to correct foot
alignment – in sports medicine, for example – are typically not appropriate for LOPS
patients, because they tend to increase loading in order to change foot function.
With respect to orthoses it should also be remembered that the ‘stock’ insoles delivered
with most therapeutic shoes are meant only as a filler and usually need to be replaced
before footwear is provided to the patient – they are typically flat and much too thin.

24.2.3.1 Cushioning
A useful conceptualization of cushioning in footwear is to consider the foot of a person
standing on a rigid flat surface compared with the same patient standing on a very thick
foam mat. The foam mat ‘cushions’ the foot by providing a surface that accommodates
to the contours of the foot, thereby distributing load to more of the plantar surface.
‘Hardness’ of the foam is an important factor. An orthosis that is too stiff will not suffi-
ciently ‘give’ to cushion, whilst an orthosis that is too soft will ‘bottom out’ and also fail
to cushion. If the material can be significantly compressed by pinching it between the
thumb and finger, then it is probably too soft for effective cushioning of the foot.
Hardness of a material can be described using the Shore A scale, foams around Shore A
Durometer 20 are most useful when used as flat material. An example would be PORON®
Urethane Foam. A foam mat of infinite thickness would completely equilibrate loading
across the foot surface. This, of course, is not possible to achieve in practice. Based on
unpublished data, thickness of 10 mm (3/8″) is suggested for a flat insole, if the shoe is
deep enough to accommodate this, since the relationship between thickness and off-
loading is curvilinear, and the shoulder of the curve is at about 10 mm (3/8″) for Shore A
Durometer 20 foam. Additionally, recent evidence has been found for the efficacy of
open and closed cell foam materials as top layer of an insole for relieving pressure under
the entire foot [7].
Orthoses also lose the ability to provide cushioning with repeated use. The practi-
tioner should examine orthoses at every visit to see if replacement is required. Tell-tale
deep impressions under bony prominences where the material may be extremely thin
are signs that the orthosis should be replaced. Some foams can lose their cushioning
capacity by taking on permanent compression even after just one day of use. Dispensing
several pairs of orthoses with a pair of new shoes is recommended if it is economically
feasible.
Another way to attempt to equally distribute load across the whole foot plantar surface
is to fully mould the orthosis to the patient’s foot [8]. Such an orthosis is typically made
based on an impression of the foot (plaster cast, foam box, or direct digital scan). This
approach does not differentiate between highly loaded areas such as are found under
bony prominences and less loaded areas where there is a lot of soft tissue between the
bone and skin, and therefore this approach does not in reality completely equilibrate
loading.
398 24 Footwear and Orthoses for People with Diabetes

24.2.3.2 Load Transfer

An additional strategy to address high pressure at bony prominences is to provide focused
load relief by transferring load to another region. Load reduction has traditionally been
accomplished by using metatarsal (MT) pads and bars, which are intended to elevate one or
more MT heads (MTHs). Recent data have provided confirmation for the efficacy of insole
construction elements such as MT pads and bars and medial arch supports in offloading the
forefoot [7, 9]. The exact location of the apex of the pad in relation to the MTHs is critical to
the effectiveness of the MT pad or bar. Studies have shown, for example, that a 5 mm differ-
ence in positioning can markedly affect the load relief provided [10] and that one standard
position is not best for all feet. Some placements can even increase pressure at the target site
[11]. This variation in response makes effective orthosis design difficult, especially since
aligning the exact location of a plantar prominence on an orthosis subjectively can be prob-
lematic. In general, the closer the apex of the MT pad or bar is placed to the MTH, without
being underneath it, the more effective it is likely to be. MT pads are available in different
heights (typically between 1/4″ and 3/8″ [6–10 mm]), and the higher pad or bar that can be
accommodated in a given shoe, the better. Based on unpublished data, the relationship
between offloading and MT bar height is also curvilinear with the shoulder of the curve in
the 10–15 mm region. MT pads usually have an adhesive to allow attachment atop an exist-
ing orthosis or can be milled or otherwise added during manufacture of the orthosis.
Load relief can also be achieved at a plantar prominence by altering the material properties
or configuration of the orthosis directly under the prominence. The usual approach is to
excavate a ‘well’ in the orthosis (and sometimes also in the midsole) directly under the promi-
nence. This well can then be filled with a soft compressible material [7], but our own research
has shown that not filling such a relief with any material provides the best offloading. The
edges of the well must be tapered such that they do not cause a local increase in pressure.

24.2.4 Rigid Outsoles (Rocker and Roller Shoes)

All of the above interventions are designed to be placed between the foot and the shoe, but
important reductions in forefoot pressure can also be obtained by making the shoes rigid
and contouring the outsole. The patient walks somewhat differently than they would in
flexible shoes and some practice is required to use the shoes comfortably and successfully.
This type of modification can be performed on almost any shoe by a shoemaker who inserts
a rigid plate (steel or carbon fibre) into the midsole. The two basic designs are the
‘rocker’ – where there is an abrupt transition between front and back of the sole, and the
roller where the transition is made by a smooth curve (Figure 24.1).
Rigid shoes can be remarkably effective, reducing peak plantar pressure in the forefoot
by 20–50%. Studies have shown that their effectiveness depends on specification of appro-
priate design parameters for rocker height, position of the rocker axis and orientation of
the axis, and that different individuals respond to the same shoe design in different ways
[12]. A rule-of-thumb from these studies is to place the axis of the rocker at approximately
55–60% of shoe length from the heel and to give the platform on which the foot rests a mini-
mum amount of toe spring (‘turn-up’ at toe). Even though such a configuration will not be
optimal for all subjects, it will almost certainly result in reduced plantar pressure at the
MTHs and toes.
 24.2 ­What is a Therapeutic Shoe for a Person Living with Diabetes 399

Roller

Roller
Radius

Take off
Rocker (% of Shoe Length)

Rocker Angle

Figure 24.1 Roller and rocker shoes: to make the outsole rigid the outer portion of the original outsole
is ground off, and a steel, carbon, or similar stay is incorporated between the original outsole remnant
and a new outsole glued on (this old and new is particularly apparent for the sports shoe below). Key
factors in the offloading efficacy of the roller or rocker shoe are their geometry – for the roller take off as
% of shoe length and radius; and for the rocker take off % and angle. See text for more details.

24.2.5 Customizing Offloading for Individuals Using Plantar

Pressure Measurement
Most of the available evidence for the use of footwear in ulcer prevention is for the preven-
tion of ulcer recurrence [4, 13]. Several prospective studies had shown a beneficial effect of
the use of therapeutic footwear compared to standard footwear in preventing ulcer recur-
rence; however, one RCT showed no effect [14]. These contrasting results have been attrib-
uted to the wide diversity of interventions and control conditions tested and the lack of
information about offloading efficacy of the footwear used, complicating the comparison
of studies in this area [15]. As we will discuss next, when offloading is documented to be
effective and the footwear is worn, the clinical trial results are positive.
Indeed, the last decade has seen much progress with the exploration of how plantar
­pressure measurement can enhance clinical practice. It has long been established that
400 24 Footwear and Orthoses for People with Diabetes

­ europathic plantar ulcers occur at sites of high plantar pressure, typically under the MTHs
n
or tips of deformed toes.
The group of Cavanagh and Ulbrecht have focussed on developing an algorithm to pre-
cisely place MT bars and reliefs in an orthosis based on each patient’s measured plantar
pressure. These orthoses also incorporate the total contact principle. Thus, shape is cap-
tured as well as barefoot plantar pressure. The orthoses are designed using computer
assisted design (CAD) and start with shape of the foot, to which offloading MT bar and
reliefs are added at locations determined by the algorithm (Figure 24.2). These orthoses are
then milled from a firm EVA and covered by a softer urethane foam. Manufacture could
occur locally, but in the US occurs typically at a central fabricating facility with the finished
orthoses shipped back to the provider. Compared to other remotely manufactured orthoses
that are reimbursed in the US as otherwise best standard of care available, these pressure-
base orthoses have been shown to offload MTHs 21–32% better and to reduce the risk of
re-ulceration sub MTHs in very high-risk patients 3.4 fold over 15 months [16]. Whilst
these orthoses also include features that offload areas of the plantar surface other than the
MTHs, efficacy in terms of preventing ulceration has not been tested at these other sites.
Barefoot plantar pressure describes the foot. It is also, however, possible to measure pres-
sure at the foot-shoe interface and this measurement speaks to the success of offloading
(Figure 24.3). The group of Bus et al. have taken the approach of using in-shoe pressure
measurement to inform iterative modification/enhancement of orthoses. Using this
approach re-ulceration was reduced by 2.6 fold in patients who used their shoes at least
80% of the time, compared with patients using orthoses made by the same experts, but not

(a)

(b)

Figure 24.2 Metatarsal pads and bars: insole (a) is designed using traditional techniques based
only on captured shape of the foot. The metatarsal pad (orange) is placed by the technician based
on the apparent location of the metatarsal heads as captured by shape; a metatarsal bar could be
placed in the same way. In (b) foot shape and barefoot pressure are combined in the design
process. Placement of the metatarsal bar (yellow) follows a pressure contour previously established
to provide optimal offloading in most patients; the relief (red) is placed in the same way.
 24.2 ­What is a Therapeutic Shoe for a Person Living with Diabetes 401

Figure 24.3 Optimizing orthosis design using in-shoe plantar pressure: peak plantar pressure
during walking, measured (a) under the foot during barefoot walking and (b) inside a shoe before and
after optimization of orthosis design using in-shoe pressure measurement. Note that the peak plantar
pressure barefoot is >1000 kPa whilst in shoe it has been reduced from 239 to 172 kPa after
modification of the shoe.

iteratively modified/enhanced based on in-shoe pressure measurement [17]. In this study

52% of the ulcers were sub MTH, 24% hallux, 20% lesser toes and 5% midfoot.
In the approach where the orthosis is designed by an algorithm based on barefoot plantar
pressure and manufactured remotely, the local expertise required is the ability to select a
shoe, fit the shoe plus orthosis, and educate/motivate the patient. In the scenario where
offloading is optimized using in-shoe pressure, the patient must also have access to a highly
skilled orthotist. A reasonable clinical pathway in a healthcare system might be to offer the
first approach to all at risk, and the second approach to those with extremely high risk,
particularly if they are not successful otherwise.

24.2.6 Offloading by Plantar Area at Risk

Heel plantar foot ulcers are typically caused by direct trauma or develop as a pressure
sore from bedrest. Once the plantar soft tissues of the heel are injured, recurrences are
common and difficult to prevent. Patients with recurring plantar heel ulcers should be
managed by an experienced orthotist and, if available, in-shoe pressure measurement
should be utilized.
Midfoot plantar foot ulcers are slightly more common than heel ulcers. They are typically
associated with a prominent base of the fifth MT, or Charcot midfoot deformity. Fifth MT
ulcers are best managed using reliefs, whilst for Charcot midfoot deformity a fully custom-
made shoe is the best option given the severe deformity present. In both cases, in shoe
pressure measurement is also very useful.
Sub MTH ulcers are the most common and, as discussed above, some combination of MT
bar, relief, and potentially rigid outsole modification is usually effective.
402 24 Footwear and Orthoses for People with Diabetes

Weight bearing toe ulcers are typically found on the distal end of toes that become
weight-bearing because of clawing or hammering. Raising the MTHs using a MT bar can
be helpful, since it also raises the toes in the shoe and reliefs – typically under all the
toes – can be incorporated. The most effective footwear modification for offloading toes is
a rigid outsole [12].

24.2.7 Footwear Modification Versus Surgery

Another option for reducing ulceration risk is to modify the foot rather than the shoe.
Procedures include surgeries to correct deformed toes, hallux rigidus, prominent MTHs,
and midfoot prominences. Achilles tendon lengthening has risks but does reduce forefoot
plantar pressure. A full discussion of how to decide between modifying the shoe vs. modi-
fying the foot is beyond the scope of this chapter. No randomized clinical trial has addressed
this question and the choice unfortunately often depends on local interest and availability
of expertise in one area or the other. Clearly not all foot deformities in a patient with LOPS
require surgery. On the other hand, dogged pursuit of ever more complex and cumbersome
footwear modifications, where a relatively simple surgical procedure could be effective, is
also inappropriate. Consideration must include patient fitness for surgery, desired activity
level, complexity of and short-term disability due to the procedure, risks of the procedure,
patient willingness to use the prescribed footwear and patient preference.
As an example, percutaneous flexor tenotomy for toe ulceration of clawed toes is a
remarkably simple and safe procedure [18], whilst footwear modifications to prevent toe
ulcers are cumbersome and not very effective. Conversely surgery on MTHs to reduce pres-
sure is more involved whilst orthoses modifications are usually effective.

24.3 ­Who Needs Therapeutic Shoes?

As discussed earlier, a person with adequate sensation (who does not have LOPS) will not
sustain foot injury due to repetitive trauma and will protect a site of injury such as caused
by stepping on an object, because such a lesion will be painful. Furthermore, such a person
will know when a shoe is too small, because it will feel uncomfortable; and will typically
doff an uncomfortable perhaps highly ‘fashionable’ shoe before it causes an injury. In
­general, therefore, diabetic people with adequate sensation do not need specific prescrip-
tion footwear. An exception might be a person with marked foot deformity, particularly in
the setting of vascular disease, where even a painful injury from ill-fitting footwear may not
heal because of the vascular disease.
The argument has been made that all people living with diabetes should only wear well-
fitting shoes to avoid development of general shoe related deformities, such as bunions, to
limit risk later if they should develop LOPS. There is no evidence for such a recommenda-
tion, and the counter argument is that limiting footwear options (and for that matter
encouraging foot directed self-care) is an unnecessary burden for a person not at increased
risk of foot injury at that time and already burdened by all the other aspects of living with
diabetes.
 24.4 ­Choosing the Appropriate Footwear for the Patient with LOP 403

24.4 ­Choosing the Appropriate Footwear

for the Patient with LOPS

The approach to choosing the shoe upper has been discussed above. The shoe upper must
accommodate the foot, its deformities, and the most appropriate orthosis. A standard shoe
may not be sufficient for this purpose, in which case an extra-depth shoe or a super-extra-
depth shoe can be used, which have, respectively, approximately 1/4″ and 1/2″ (6 and
13 mm) of additional depth in the toe box. Occasionally it is necessary to provide a custom
moulded (US)/bespoke (UK) shoe just to have enough room for a sufficiently thick ortho-
sis, particularly if this is for a patient with dorsal deformity such as dorsally dislocated toes.
Based on the recently published studies summarized above, it could be argued that a
patient with LOPS should have their barefoot plantar pressure measured and should have
orthoses designed based on their measured barefoot plantar pressure, or that orthoses and
potentially outsoles should be adjusted based on measured in-shoe plantar pressure to
assure ideal offloading. This will, however, likely never be optimal care because research
has also shown that only a minority of patients with LOPS with even very high plantar
pressure ever ulcerate. Therefore, the first line of plantar protection for a patient with
LOPS but no other risk factors is a quality sports shoe, as long as any deformity can be
accommodated. Sport shoes significantly reduce plantar pressures compared to conven-
tional shoes [19]. An equivalent would be a depth dress shoe with a thick flat or even
moulded orthosis.
Patients with prior ulceration, on the other hand, have risk of recurrent ulceration
40–50% in the first year [20] and such patients certainly should be provided enhanced foot-
wear and ideally orthoses and shoes optimized using plantar pressure measurement, as
should patients with abundant or hemorrhagic callus, before they actually ulcerate [20]. If
these tools are not available then all the components of orthosis design discussed
above – appropriate materials, moulding, maximum available thickness, MT bar of maxi-
mum available height, reliefs, rigid outsole modification – should be incorporated, as
appropriate. These patients must pay special attention to footwear for the remainder of
their lives. It is only after an ulcer has healed that definitive footwear can be provided.
Specifying the details of prescription footwear is often considered to be a task of the shoe
technician, orthotist or pedorthist, and not the clinician. However, it is important for the
clinician who is the primary provider of foot care to know what the available options are.
The higher the risk of foot ulceration and the more deformity present, the more customized
the shoe should be. Only patients with severe foot deformity or other special problems will
require custom moulded (US)/bespoke (UK) shoes that one of the specialists mentioned
above can provide. This is shown schematically in the ‘footwear pyramid’ in Figure 24.4.

24.4.1 Shoe ‘Break-in’

It is customary to encourage patients to not use newly provided shoes full-time immedi-
ately. Rather ‘break-in’ as recommended where shoes are worn initially perhaps only an
hour in the morning and an hour in the afternoon, with increasing wear day by day over
two weeks. Intuitively this makes sense because we all know that shoes accommodate to a
foot with wear and additionally a particular shoe may not be ‘sufficient’ for a patient despite
404 24 Footwear and Orthoses for People with Diabetes

Figure 24.4 The footwear pyramid.

Activity Foot
Level Custom Deformity
Molded
Rigid Sole ExD
Extra-Depth shoes

Athletic shoes

of the provider’s best effort. Careful twice a day self-examination of the feet, perhaps with
temperature monitoring [20], must be a component of this break-in period. There are no
studies that would inform how long the ‘break-in’ period should be and how it should be
structured.

24.4.2 The Diabetic Patient with an Ulcer

There is no evidence that any shoe utilized for every day wear to prevent an ulceration
provides sufficient offloading to heal an ulceration, even though it is common practise to
use such shoes for ulcer healing in many settings throughout the world [3].

24.4.3 The Diabetic Patient with a Recently Healed Ulcer

The first few weeks following return to normal ambulation after ulcer healing is a period of
very high risk [16], and it may be preferable to transition the patient into new therapeutic
footwear by providing a very well-cushioned walking splint or orthopaedic walker to ena-
ble the fragile new tissue to consolidate. Another option for this purpose is a bivalve total
contact cast. As above, transition to new footwear should always be gradual, and such
‘break in’ can utilize one of these transition devices as the alternative to the new shoes.

24.4.4 The Charcot Patient

A full discussion of shoe-gear for the patient with a quiescent Charcot foot is beyond the
scope of this chapter. However, it is clear from the usual severity of the midfoot deformity
of a patient with a Charcot foot that custom moulded (USA)/bespoke (UK) footwear is
often the recommended treatment.

24.4.5 Going Home with the Patient

It is all too easy to carefully design shoes for a patient, dispense them, and then have them
sit in a closet, be given to a friend, etc. Some patients conclude that the therapeutic shoes
are only for going outdoors; thus addressing what is worn in the home, at night to go to the
bathroom, etc., must be a priority in each case. Research has shown that patients are less
adherent with footwear use at home [21], where many take the most steps! Some patients
save their special shoes for special occasions, and others simply took them home to please
the provider. Some patients are farmers and some steelworkers; some like to play golf, and
 24.4 ­Choosing the Appropriate Footwear for the Patient with LOP 405

others to ride horses. All activities that the person may do must be considered and appropri-
ate footwear for all activities must be provided, if possible. Insurance coverage sometimes
gets in the way of this ideal. In that case, the therapeutic shoes provided as a priority should
address the activity in the patient’s life that puts most stress on their feet for the longest
amount of time; so perhaps plantar pressure enhanced shoes for the factory floor and sports
shoes for home. Overshoes for snow and mud are a reasonably inexpensive option.

24.4.5.1 Instability
Patients with LOPS report 15-fold more injuries during walking or standing than do dia-
betic patients without LOPS [22].
The reason for this balance problem is that balance is dependent on three inputs about
body position in space: proprioception from the feet, vision, and vestibular. Obviously, in
a patient with LOPS, proprioception is degraded. Unfortunately, the footwear interven-
tions utilized for prevention of plantar injury decrease proprioceptive feedback from the
plantar surface further [23]. In fact, an approach used experimentally to degrade foot pro-
prioception in healthy subjects is standing on foam! Rigid outsoles may make balance
worse yet, depending on how this is assessed [24, 25]. Some patients will complain that the
therapeutic shoes worsen their balance, whilst others may simply not wear them without
telling the provider.
It is important to discuss this issue with patients a priori and suggest mitigation. A walking
stick will enhance the feeling of security (by providing proprioception through the hand),
particularly on uneven ground. Many younger patients do not want a cane but will consider
a telescopic aluminium hiking pole. Similarly, a hand running against the wall, counter, etc.
can be helpful. When standing it is helpful to touch a wall, tree, counter, chair back, etc. with
the hand or hip.
Reaching and therefore looking up degrades vestibular input, so when looking up it is
always best to lean against something. Stairs are the most dangerous place in a house. It is
best to always hold the hand-rail and to try to have someone else carry anything that must
be held in both hands (laundry basket) or use a backpack. Only go up and down stairs that
are well lit. Also, always turn the lights on, even going to the bathroom at night; be sure you
can turn the light on from your bed before walking across the room.

24.4.5.2 Adherence to Wearing Therapeutic Footwear

The most advanced and well-designed prescription shoe can only be effective if worn by the
patient on a continuing basis. However, a number of studies have shown that consistent use
of such footwear is rarely the case and that poor adherence with wearing therapeutic foot-
wear is associated with increased risk of ulceration (e.g. Bus et al. [17, 26]). Patients can
often use their therapeutic shoes for the majority of the time only to fail, and ulcerate, while
on holiday or attending a special event such as a wedding at which they felt the need to wear
attractive (but unsafe) footwear [27].
No research has yet established the optimal approach to maximize patient adherence to
therapeutic footwear use. Knowledge is important, but insufficient by itself for behaviour
change. Person-centred communication, shared decision making and other components of
motivational interviewing are likely to be helpful but have not yet been rigorously investi-
gated in this setting [28–31].
406 24 Footwear and Orthoses for People with Diabetes

24.5 ­Summary and Future Trends

Older studies of prescription footwear for high-risk diabetic patients had equivocal results.
In these older studies plantar and non-plantar ulcer outcomes were often mixed, and with
respect to the plantar surface typically neither offloading efficacy nor consistent use of the
footwear by the patient were validated. Fortunately, research in the last decade has now
clearly demonstrated that when shoes do effectively offload highly loaded points on the
plantar surface and are worn by the patient consistently, the risk of plantar ulceration is
reduced.
It is now also clear that plantar pressure measurement can add significant value to foot-
wear design, particularly for high-risk patients. As clinicians we must improve our ability
to stratify risk, and administrators must enable plantar pressure technology in healthcare
systems for higher risk patients.
Last, and no less important, clinicians must improve ability to help patients achieve foot
care and footwear behaviours to reduce the risk of ulceration.

­Acknowledgement

We gratefully acknowledge the contribution to this chapter of our colleague and mentor
Peter Cavanagh, PhD, DSc, who was a co-author of this chapter in the previous editions.

­Conflict of Interest Statement

Dr Ulbrecht is a part owner of DIApedia LLC, an R&D company active in the field of dia-
betes related foot problems. DIApedia LLC has developed off-loading orthoses for at-risk
diabetic patients that are currently being sold in the US and Europe.

­References

1 Schaper, N.C., Van Netten, J.J., Apelqvist, J. et al. (2016). Prevention and management of
foot problems in diabetes: a summary guidance for daily practice 2015, based on the IWGDF
guidance documents. Diabetes Metab. Res. Rev. 32 (Suppl 1): 7–15.
2 Crawford, F., Cezard, G., Chappell, F.M. et al. (2015). A systematic review and individual
patient data meta-analysis of prognostic factors for foot ulceration in people with diabetes:
the international research collaboration for the prediction of diabetic foot ulcerations
(PODUS). Health Technol. Assess. 19 (57): 1–210.
3 Bus, S.A., Armstrong, D.G., van Deursen, R.W. et al. (2016). IWGDF guidance on footwear
and offloading interventions to prevent and heal foot ulcers in patients with diabetes.
Diabetes Metab. Res. Rev. 32 (Suppl 1): 25–36.
4 Bus, S.A., van Netten, J.J., Lavery, L.A. et al. (2016). IWGDF guidance on the prevention of
foot ulcers in at-risk patients with diabetes. Diabetes Metab. Res. Rev. 32 (Suppl 1): 16–24.
  ­Reference 407

5 Harrison, S.J., Cochrane, L., Abboud, R.J., and Leese, G.P. (2007). Do patients with diabetes
wear shoes of the correct size? Int. J. Clin. Pract. 61 (11): 1900–1904.
6 Nixon, B.P., Armstrong, D.G., Wendell, C. et al. (2006). Do US veterans wear appropriately
sized shoes? The veterans affairs shoe size selection study. J. Am. Podiatr. Med. Assoc. 96
(4): 290–292.
7 Arts, M.L., de Haart, M., Waaijman, R. et al. (2015). Data-driven directions for effective
footwear provision for the high-risk diabetic foot. Diabet. Med. 32 (6): 790–797.
8 Nouman, M., Leelasamran, W., and Chatpun, S. (2017). Effectiveness of total contact
orthosis for plantar pressure redistribution in neuropathic diabetic patients during
different walking activities. Foot Ankle Int. 38 (8): 901–908.
9 Guldemond, N.A., Leffers, P., Schaper, N.C. et al. (2007). The effects of insole
configurations on forefoot plantar pressure and walking convenience in diabetic patients
with neuropathic feet. Clin. Biomech. 22 (1): 81–87.
10 Hayda, R., Tremaine, M.D., Tremaine, K. et al. (1994). Effect of metatarsal pads and their
positioning: a quantitative assessment. Foot Ankle Int. 15 (10): 561–566.
11 Holmes, G.B. Jr. and Timmerman, L. (1990). A quantitative assessment of the effect of
metatarsal pads on plantar pressures. Foot Ankle 11 (3): 141–145.
12 Chapman, J.D., Preece, S., Braunstein, B. et al. (2013). Effect of rocker shoe design features
on forefoot plantar pressures in people with and without diabetes. Clin. Biomech. (Bristol,
Avon) 28 (6): 679–685.
13 van Netten, J.J., Price, P.E., Lavery, L.A. et al. (2016). Prevention of foot ulcers in the
at-risk patient with diabetes: a systematic review. Diabetes Metab. Res. Rev. 32 (Suppl 1):
84–98.
14 Bus, S.A., van Deursen, R.W., Armstrong, D.G. et al. (2016). Footwear and offloading
interventions to prevent and heal foot ulcers and reduce plantar pressure in patients with
diabetes: a systematic review. Diabetes Metab. Res. Rev. 32 (Suppl 1): 99–118.
15 Bus, S.A. (2016). The role of pressure offloading on diabetic foot ulcer healing and
prevention of recurrence. Plast. Reconstr. Surg. 138 (3 Suppl): 179S–187S.
16 Ulbrecht, J.S., Hurley, T., Mauger, D.T., and Cavanagh, P.R. (2014). Prevention of recurrent
foot ulcers with plantar pressure-based in-shoe orthoses: the CareFUL prevention
multicenter randomized controlled trial. Diabetes Care 37 (7): 1982–1989.
17 Bus, S.A., Waaijman, R., Arts, M. et al. (2013). Effect of custom-made footwear on foot
ulcer recurrence in diabetes: a multicenter randomized controlled trial. Diabetes Care 36
(12): 4109–4116.
18 Rasmussen, A., Bjerre-Christensen, U., Almdal, T.P., and Holstein, P. (2013). Percutaneous
flexor tenotomy for preventing and treating toe ulcers in people with diabetes mellitus. J.
Tissue Viability 22 (3): 68–73.
19 Perry, J.E., Ulbrecht, J.S., Derr, J.A., and Cavanagh, P.R. (1995). The use of running shoes to
reduce plantar pressures in patients who have diabetes. J. Bone Joint Surg. Am. 77 (12):
1819–1828.
20 Armstrong, D.G., Boulton, A.J.M., and Bus, S.A. (2017). Diabetic foot ulcers and their
recurrence. N. Engl. J. Med. 376 (24): 2367–2375.
21 Waaijman, R., Keukenkamp, R., de Haart, M. et al. (2013). Adherence to wearing
prescription custom-made footwear in patients with diabetes at high risk for plantar foot
ulceration. Diabetes Care 36 (6): 1613–1618.
408 24 Footwear and Orthoses for People with Diabetes

22 Cavanagh, P.R., Derr, J.A., Ulbrecht, J.S. et al. (1992). Problems with gait and posture in
neuropathic patients with insulin-dependent diabetes mellitus. Diabet. Med. 9 (5): 469–474.
23 Paton, J., Glasser, S., Collings, R., and Marsden, J. (2016). Getting the right balance:
insole design alters the static balance of people with diabetes and neuropathy. J. Foot
Ankle Res. 9: 40.
24 Ghomian, B., Kamyab, M., Jafari, H. et al. (2016). Rocker outsole shoe is not a threat to
postural stability in patients with diabetic neuropathy. Prosthet. Orthot. Int. 40 (2): 224–230.
25 Vieira, E.R., Guerrero, G., Holt, D. et al. (2014). Limits of stability and adaptation to
wearing rocker bottom shoes. Foot Ankle Int. 35 (6): 607–611.
26 Waaijman, R., de Haart, M., Arts, M.L. et al. (2014). Risk factors for plantar foot ulcer
recurrence in neuropathic diabetic patients. Diabetes Care 37 (6): 1697–1705.
27 Armstrong, D.G., Dang, C., Nixon, B.P., and Boulton, A.J. (2003). The hazards of the
holiday foot: persons at high risk for diabetic foot ulceration may be more active on
holiday. Diabet. Med. 20 (3): 247–248.
28 van Netten, J.J., Francis, A., Morphet, A. et al. (2017). Communication techniques for
improved acceptance and adherence with therapeutic footwear. Prosthet. Orthot. Int. 41 (2):
201–204.
29 Gabbay, R.A., Kaul, S., Ulbrecht, J. et al. (2011). Motivational interviewing by podiatric
physicians: a method for improving patient self-care of the diabetic foot. J. Am. Podiatr.
Med. Assoc. 101 (1): 78–84.
30 Price, P. (2016). How can we improve adherence? Diabetes Metab. Res. Rev. 32 (Suppl 1):
201–205.
31 Keukenkamp, R., Merkx, M.J., Busch-Westbroek, T.E., and Bus, S.A. (2018). An explorative
study on the efficacy and feasibility of the use of motivational interviewing to improve
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Med. Assoc. 108 (2): 90–99.
 409

25

The Diabetic Foot in Remission

Tanzim Khan1, Sicco A. Bus2, Andrew J.M. Boulton3,4, and David G. Armstrong1
1
Division of Vascular Surgery and Endovascular Therapy, The Southwestern Academic Limb Salvage Alliance, Department of
Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
2
Amsterdam UMC, location Academic Medical Center, Department of Rehabilitation Medicine, Amsterdam Movement
Sciences, University of Amsterdam, Amsterdam, The Netherlands
3
Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK
4
University of Miami, Miam, FL, USA

25.1 ­The Diabetic Foot in Remission

Once a diabetic foot wound has healed, the regenerated cutaneous tissue does not have the
strength of the adjacent skin and is vulnerable to mechanical forces, such as pressure and
shear. In addition, healed full-thickness plantar ulcers may have a significant deficit in the
adipose tissue that provides cushion to the skin during weight bearing. Studies have shown
that one of the most substantial indicators for a diabetic foot ulceration is the history of a
prior foot ulcer [1, 2]. Armstrong et al. performed a review of 19 studies, which demon-
strated a 40% recurrence rate of ulcerations at one year, 60% within three years, and 65% in
a five year period [3]. These significant numbers demonstrate the need for protection of the
foot even after an ulceration has healed. Casting and offloading of the foot do not correct
deformities of the lower extremity, and even those who have received reconstructive sur-
gery of the musculoskeletal and arterial systems are still afflicted with the neuropathic
component of diabetes, placing them at continued risk for diabetic foot complications due
to a lack of pain feedback.
It is not uncommon for patients and their families to stray away from follow-up and
adherence to treatment, as they believe they no longer have issues with their foot. This
mindset bears heavy consequences, as those who are adherent to treatment protocols have
significantly better outcomes than those who are non-adherent [4, 5]. Barefoot walking, ill
fitting shoes, and the lack of foot monitoring contribute to the recurrence rate of ulcera-
tions in these patients. Armstrong and Mills proposed a change in syntax, to reflect the
high recurrence rate, and stress the compliance needed by patients to maintain ulcer-free
days [6]. Healed ulcers were to be considered in remission rather than being simply labelled
as healed. The term remission provides a means to communicate the severity of diabetic
foot ulcerations to patients, which have mortality and complication rates comparable to

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
410 25 The Diabetic Foot in Remission

Diabetic Foot Remission

Offloading

Patient Education

Self-Examination

Professional Foot Care

Persistent Monitoring Technologies

Figure 25.1 The necessary components needed to maximize ulcer-free days in diabetic foot
remission. If any of the components are failing, the ring will be broken, and incidence of relapse
will increase.

those of aggressive cancers [6, 7]. A diabetic foot ulcer in remission indicates to the patient
that a lifetime of follow-up and preventative treatment will be needed to preclude devastat-
ing complications from arising in the future. Maintenance of remission requires several
components to work concurrently to sustain ulcer-free, hospital-free, and activity rich days
(Figure 25.1).

25.2 ­Maintaining Remission

25.2.1 Offloading
Distributing pressure over a larger surface area is a key principal in maintaining a diabetic
foot in remission. In a study by Owings et al., the authors established an in-shoe plantar
pressure threshold of 200 kPa, in which those who had fallen under this pressure had
remained ulcer-free [8]. In the same study, barefoot plantar pressure at a site of previous
ulceration averaged around 506 kPa, well above the suggested in-shoe pressure of 200 kPa
[8]. Other studies have since supported this pressure threshold as target for footwear pre-
scription [9, 10]. Normal shoe gear places the insensate patient at risk for re-ulceration, and
can be a source of self-induced injury if not fitted properly. Offloading devices such as
custom diabetic shoes and insoles, have demonstrated the ability to reduce plantar pressure
and shear, and in effect reduce re-ulceration rates [11–16]. Therefore, it would be justifiable
to state that prescribed therapeutic footwear are a mainstay for the management of patients
in remission, and adherence to walking in these devices are essential to maintaining ulcer-
free days [14].
 25.2 ­Maintaining Remissio 411

25.2.2 Surgical Offloading

Surgical management of deformities and pathomechanics of the foot and ankle are consid-
ered therapeutic procedures to maintain diabetic foot ulceration remission. The goal of
diabetic foot surgery is to eliminate forces that increase peak plantar pressures and osseous
prominences that are susceptible to friction and shear. Surgical offloading is an accepted
method of offloading the diabetic foot, and is often employed when ulcerations are refrac-
tory to conservative treatment or early aggressive treatment is needed to create a planti-
grade foot. One must be cautious of patient selection in diabetic foot surgery, as there is an
increased risk of complications compared to their non-diabetic equivalents [17, 18].
Limited ankle dorsiflexion has been associated with diabetic foot ulcers [19], and is prev-
alent in those who have elevated peak plantar pressures and history of neuropathic ulcers
[20]. This is often contributed to an Achilles tendon contracture, also known as equinus.
Percutaneous tendo-achilles lengthening (TAL) has demonstrated a 27–28% reduction in
peak plantar pressures in the foot [21]. The TAL is a powerful tool that can be performed as
a stand-alone procedure, as well as an adjunct to other operative techniques. Again, the
possible complications of this procedure have to be considered before employing it [18].
Digital deformities such as hammertoes and claw toes are often the source of non-plantar
diabetic foot ulcerations, as well as increased pressure to the plantar heads due to retro-
grade plantarflexion and distal migration of the plantar fat pad [22]. Surgical correction of
these deformities consists of joint arthroplasties, tendon tenotomies, and metatarsal head
resections. A combination of these procedures aims to decrease the incidence of ulceration
at the distal tip, dorsal interphalangeal joint, and sub-metatarsal tissue in those diabetic
foot remission [23].
Deformity and instability are hallmark features of Charcot Neuroarthropathy. Fractures,
subluxations, dislocations, and bone destruction result in deformities, the most common
being the ‘rocker-bottom’ seen in the midfoot tarsal bones [24]. Surgical management of
Charcot foot ranges from bone exostectomy to allow for the fitting of therapeutic footwear,
to osseous reconstruction with the use of internal and external fixation to create a planti-
grade foot [24]. Surgical management of the Charcot foot is a management strategy that
works in conjunction with therapeutic offloading devices.
The loss of adipose tissue after the healing of a plantar foot ulcer places the plantar skin
at risk for re-ulceration, especially when there is a prominent subcutaneous osseous struc-
ture present. In order to maintain remission, Luu et al. introduced a technique implement-
ing autologous adipose tissue to the sole of the foot [25]. They harvested 25 cc of adipose
tissue from the abdomen and injected the fat graft into the plantar areas of the foot demon-
strating lack of soft tissue bulk and fat pad atrophy [25]. Follow-up demonstrated MRI
evidence of fat graft incorporation and lack of clinical signs of increased pressure or ulcera-
tion [25].

25.2.3 Patient Education and Self-Management

The patient’s participation in maintaining remission is a must if recurrence risk is to be
reduced. The first step in this process is educating the patient on the severity of diabetic
foot ulcers and the prognosis that they carry. The use of the term remission rather than
412 25 The Diabetic Foot in Remission

healed wound, should instil a sense of severity into the mind of the patient during coun-
selling [6]. It is important for the clinician to understand that many neuropathic patients
may not comprehend the precautions and modalities needed to keep them ulcer-free, as
they do not feel pain. Without the sense of pain, these individuals often do not believe
they are having issues with their foot, as they feel as if they are asymptomatic.
Reinforcement has to be provided by caregivers, with reiteration that custom shoes with
insoles, Charcot restraint orthotic walkers (CROW), or any other prescribed therapeutic
offloading devices, must be worn as they have shown to be strong protectors against ulcer-
ation and recurrence [9, 18].
Self-management is the patient’s role in practising active prevention of diabetic foot
ulcers. This includes adopting preventive foot behaviours such as avoiding walking bare-
foot, checking the temperature of bathwater, maintaining proper hygiene, moisturizing the
feet, and performing daily self-inspection [26]. Self-examination is a mandatory process in
retaining a state of remission, and will often require a mirror for visualization of the plan-
tar and posterior foot, especially in those with limited joint mobility or with marked obe-
sity. Visualization and palpation of a hemorrhagic callus in the plantar foot is analogous to
inspecting for a breast lump during a breast self-exam (Figure 25.2). The presence of blis-
tering, subcutaneous haemorrhage, and callus, especially a hemorrhagic callus, are early
signs that are highly suggestive of impending ulceration [3, 9]. Any of these early signs
should indicate to the patient to follow up with their foot care provider for intervention to
avert active foot ulceration.
The patient practising preventative foot behaviours should still maintain follow up with
a foot care professional every one to three months [27, 28]. The clinician’s goals should be
to inspect the feet for any cutaneous manifestations that are indicative of excessive pres-
sure, inspect offloading devices for proper pressure redistribution, as well as temperature
inspection for signs of inflammation [3]. Along with these visits, one-on-one counselling

Callus = Breast Lump?

Figure 25.2 A haemorrhagic callus on the plantar foot is a warning sign for foot ulceration just as
a breast lump is for breast cancer.
 25.3 ­Conclusio 413

should be used to reinforce preventative measures required to promote ulcer-free days,

which has shown to demonstrate higher rates of foot self-management [26].

25.2.4 Persistent Monitoring Technologies

Advancements in technology play an integral part in moving forward to decrease recur-
rence rates for ulceration. The development of technology that allows early detection of
imminent danger to cutaneous tissue provide objective data to clinicians and patients that
alert them to initiate management strategies to avoid relapse of the diabetic foot. Signs of
calor, erythema, and elevated peak plantar pressures are markers that precede the develop-
ment of foot ulceration [29]. The use of thermometry is one of the techniques to objectively
assess temperature deviations in the foot as a marker for inflammation and ulcer risk.
Temperature differences have shown to be 4.8 times greater at the site of ulceration in the
week preceding its development [30]. In a randomized control trial by Lavery et al., those
who used an infrared thermometer daily to inspect for temperature increases in the foot,
had a fourfold reduction in risk of developing a diabetic foot ulcer [31]. The use of ther-
mometry monitoring serves as a useful tool in maintaining diabetic foot remission, however
has several barriers that have prevented widespread implementation. Factors include avail-
ability of such devices, lack of reimbursement of devices by insurance companies, and the
perceived monotonous task of checking foot temperatures on a daily basis for a lifetime [3].
The use of wearable technology ushers in the future of monitoring therapies for the
foot in remission. The SmartSox is a wearable textile that provides information regarding
pressure levels, temperatures, and lower extremity joint extremity angles. The goal of
the device is to assess the key parameters that place the diabetic foot at risk for foot
ulceration [32].
The SurroSense Rx is a smart insole that monitors for sustained plantar pressure and
alerts the operator by notifications via smart watches to offload their weight [33]. Although
it is not a wearable device, a smart mat has been developed to allow daily foot temperature
monitoring, as one would step on a scale to measure weight. The simplicity of use could
provide increased adherence by patients and provide the benefits of thermometry moni-
toring for reduction in recurrence of ulcerations [34].

25.3 ­Conclusion

The closure of a diabetic foot ulceration is the beginning of a lifetime campaign in main-
taining the diabetic foot in remission. The use of offloading devices and offloading surgical
procedures have shown to reduce risks of recurrence in these ulceration prone patients.
Intimate conversations with patients regarding the morbidity and mortality need to estab-
lish the necessity in compliance with therapeutic shoe gear, professional follow-up, as well
as self-care and self-examination. Although not widely accepted, technologies that monitor
temperature and peak plantar pressure levels can provide care providers and patients early
warnings to possibly halt relapse of diabetic foot ulceration. The future of diabetic foot
remission lies on the interconnection between offloading, improved patient compliance
and education, as well as persistent monitoring technologies.
414 25 The Diabetic Foot in Remission

­References

1 Crawford, F., Cezard, G., Chappell, F.M. et al. (2015). A systematic review and individual
patient data meta-analysis of prognostic factors for foot ulceration in people with diabetes:
the international research collaboration for the prediction of diabetic foot ulcerations
(PODUS). Health Technol. Assess. 19 (57): 1–210.
2 Monteiro-Soares, M., Boyko, E.J., Ribeiro, J. et al. (2012). Predictive factors for diabetic foot
ulceration: a systematic review. Diabetes Metab. Res. Rev. 28 (7): 574–600.
3 Armstrong, D.G., Boulton, A.J.M., and Bus, S.A. (2017). Diabetic foot ulcers and their
recurrence. N. Engl. J. Med. 376 (24): 2367–2375.
4 Bus, S.A. and van Netten, J.J. (2016). A shift in priority in diabetic foot care and research:
75% of foot ulcers are preventable. Diabetes Metab. Res. Rev. 32 (Suppl 1): 195–200.
5 Netten, J.J., Price, P.E., Lavery, L.A. et al. (2016). Prevention of foot ulcers in the at-risk
patient with diabetes: a systematic review. Diabetes Metab. Res. Rev. 32 (S1): 84–98.
6 Armstrong, D.G. and Mills, J.L. (2013). Toward a change in syntax in diabetic foot care:
prevention equals remission. J. Am. Podiatr. Med. Assoc. 103 (2): 161–162.
7 Armstrong, D.G., Wrobel, J., and Robbins, J.M. (2007). Guest editorial: are diabetes-related
wounds and amputations worse than cancer? Int. Wound J. 4 (4): 286–287.
8 Owings, T.M., Apelqvist, J., Stenström, A. et al. (2009). Plantar pressures in diabetic
patients with foot ulcers which have remained healed. Diabet. Med. 26 (11): 1141–1146.
9 Waaijman, R., de Haart, M., Arts, M.L.J. et al. (2014). Risk factors for plantar foot ulcer
recurrence in neuropathic diabetic patients. Diabetes Care 37 (6): 1697–1705.
10 Waaijman, R., Arts, M.L.J., Haspels, R. et al. (2012). Pressure-reduction and preservation in
custom-made footwear of patients with diabetes and a history of plantar ulceration. Diabet.
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11 Busch, K. and Chantelau, E. (2003). Effectiveness of a new brand of stock “diabetic” shoes
to protect against diabetic foot ulcer relapse. A prospective cohort study. Diabet. Med. 20
(8): 665–669.
12 Ulbrecht, J.S., Hurley, T., Mauger, D.T., and Cavanagh, P.R. (2014). Prevention of recurrent
foot ulcers with plantar pressure–based in-shoe Orthoses: the CareFUL prevention
multicenter randomized controlled trial. Diabetes Care 37 (7): 1982–1989.
13 Peters, E.J.G., Armstrong, D.G., and Lavery, L.A. (2007). Risk factors for recurrent diabetic
foot ulcers. Diabetes Care 30 (8): 2077–2079.
14 Bus, S.A., Waaijman, R., Arts, M. et al. (2013). Effect of custom-made footwear on foot
ulcer recurrence in diabetes: a multicenter randomized controlled trial. Diabetes Care 36
(12): 4109–4116.
15 Arts, M.L.J., de Haart, M., Waaijman, R. et al. (2015). Data-driven directions for effective
footwear provision for the high-risk diabetic foot. Diabet. Med. 32 (6): 790–797.
16 Owings, T.M., Woerner, J.L., Frampton, J.D. et al. (2008). Custom therapeutic insoles based
on both foot shape and plantar pressure measurement provide enhanced pressure relief.
Diabetes Care 31 (5): 839–844.
17 Frykberg, R.G., Bevilacqua, N.J., and Habershaw, G. (2010). Surgical off-loading of the
diabetic foot. J. Am. Podiatr. Med. Assoc. 100 (5): 369–384.
18 Bus, S.A., Armstrong, D.G., van Deursen, R.W. et al. (2016). IWGDF guidance on footwear
and offloading interventions to prevent and heal foot ulcers in patients with diabetes.
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Clin Biomech 43: 8–14.
21 Armstrong, D.G., Stacpoole-Shea, S., Nguyen, H., and Harkless, L.B. (1999). Lengthening
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healing wounds and extending ulcer-free days in remission. CWCMR. 4: 83–88.
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25 Luu, C.A., Larson, E., Rankin, T.M. et al. (2016). Plantar fat grafting and tendon balancing
for the diabetic foot ulcer in remission. Plast. Reconstr. Surg. Glob. Open 4 (7): e810.
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reduces the risk for diabetic foot ulceration in high-risk patients. Am. J. Med. 120 (12):
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recurrence in high-risk patients: use of temperature monitoring as a self-assessment tool.
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 417

26

Setting up a Diabetic Foot Clinic

Michael E. Edmonds and N.L. Petrova
Diabetic Foot Clinic, King’s College Hospital NHS Foundation Trust, London, UK

26.1 ­Natural History of the Diabetic Foot

When setting up a diabetic foot clinic, one should understand that the natural history of
the diabetic foot is aggressive and complex, and a special form of care is needed. Three
dangerous pathologies come together in the diabetic foot: neuropathy, ischaemia, and
infection. Over the last 20 years there has been an ever-increasing preponderance of
ischaemic/neuroischaemic ulcers which are now more common than the neuropathic
ulcers [1]. An analysis conducted at the Diabetic Foot Clinic, King’s College Hospital,
London, indicated that the prevalence of neuroischaemic ulcers has been rising since the
1990s from approximately one-third of patients to over 50%, therefore developing into the
most common aetiology of diabetic foot ulcers [2]. The recent large European cohort stud-
ies of patients with diabetes and foot ulcers confirm that at least half are of neuroischae-
mic or ischaemic origin [3–5].
In the natural history of the diabetic foot, both neuropathic and neuroischaemic feet
undergo repeated crises, often starting with minor trauma, aggravated by neuropathy and/
or ischaemia, and accelerated by the swift onset of infection. This can quickly lead to tissue
necrosis which is the fundamental hallmark of the natural history of the diabetic foot.
Progress towards necrosis can be so rapid and devastating that it has come to be regarded it
as a ‘diabetic foot attack’ similar to the heart and brain attacks of the coronary and cerebro-
vascular systems. As a result of neuropathy, the signs and symptoms of external physical
insults may be minimal. Local signs of infection such as pain or tenderness may be dimin-
ished or even absent and this often delays the patient’s presentation. Despite minimal
signs, the pathology emanating from such insults proceeds rapidly without the patient or
medical attendants being fully aware of it. For these reasons, patient’s presentation is often
late and the end stage of tissue death is quickly reached. A ‘diabetic foot attack’ can quickly
reach the point of no return, with overwhelming necrosis.
As well as ulceration and infection, the Charcot foot is also a major problem in diabetic
foot clinics. A marked increase in the reported cohorts of cases has been noted

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
418 26 Setting up a Diabetic Foot Clinic

(see Chapter 19). The Charcot foot can rapidly lead to deformity, ulceration, and infection
and in the hind foot to severe instability. Either infection or instability can lead to major
amputation.

26.2 ­Principles of Care of the Diabetic Foot

In response to this complex and aggressive natural history, certain principles of care
should be followed to achieve successful management of the diabetic patient. There
should be open access for urgent foot problems to allow emergency visits to the clinic.
The window of opportunity for intervention is limited and the diabetic foot clinic must
be set up to seize such an opportunity. In all aspects of diabetic foot presentation, both
emergency and by appointment, ‘Time is Tissue’ and speed is of the essence both in diag-
nosis and delivery of co-ordinated multidisciplinary care of ulceration, infection, and the
Charcot foot [6, 7]. In setting up a successful diabetic foot clinic, it is necessary to plan to
uphold these principles. In order to do so, it is essential to acquire the appropriate space
and personnel, both of which should be organised to carry out the functions of the clinic.
Space, personnel, and organisation will now be discussed separately although there is
some overlap between discussing the role of specific personnel and the organisation of
the clinic.

26.3 ­Space for the Diabetic Foot Clinic

The diabetic foot clinic should be situated in identifiable outpatient space, which is
accessible to patients who have mobility problems. Sufficient space for examination and
treatment rooms is essential as patient flow is important to efficient working of the
clinic and patient satisfaction [8]. The clinic should be a central focus taking on the role
of an ‘operations centre’ for diabetic foot care within the local vicinity but it may also
receive referrals from afar. The outpatient space should be within or connected to a
hospital, as patients with diabetic foot problems require frequent hospital services. It is
necessary for the diabetic foot clinic to work closely with other departments of the hos-
pital notably the vascular laboratory and diagnostic radiology for vascular imaging and
angioplasty and the departments of vascular and orthopaedic surgery for arterial distal
bypass and surgical reconstruction. It is ideal for the diabetic foot clinic to be linked to
a specific hospital ward which continues to adhere to the team approach and provide
continuity.
In view of the preponderance of ischaemic and neuroischaemic ulcers, it is important
that the diabetic foot clinic has close links to a non-invasive vascular laboratory to facilitate
initial diagnosis of ischaemia, decisions regarding the mode of revascularisation, follow-up
care, and suitable and accessible testing on a regular basis [9]. If referral of patients to a
vascular laboratory is not possible, there should be appropriate space and equipment in the
diabetic foot clinic, together with suitable personnel to perform basic vascular investiga-
tions such as Ankle Brachial Pressure Index and Doppler sonograms.
 26.4 ­Personnel for the Diabetic Foot Clini 419

Ideally, a meeting room should be made available in the diabetic foot clinic for team
meetings to discuss patients, ongoing clinic issues, and for educational activities including
seminars and lectures.

26.4 ­Personnel for the Diabetic Foot Clinic

Successful management of the diabetic foot needs the expertise of a multidisciplinary care
team which provides integrated care focused in a diabetic foot clinic [10]. No single person
can take control of the diabetic foot. Members of the team comprise podiatrist, physician,
nurse, orthotist, radiologist, and surgeon, including vascular surgeon, orthopaedic ­surgeon,
and plastic surgeon. Other important members are the vascular scientist, microbiologist,
pharmacist, physiotherapist, occupational therapist, dermatologist, and psychiatrist. The
patient is an important member of the team and can provide useful feedback information
as a service user [8]. The diabetic foot team works closely together, within the focus of the
diabetic foot clinic, but also in inpatient areas including wards, operating theatres, and
angiography suites. It also meets regularly for ward rounds and X-ray conferences. Some
roles may overlap, depending on local expertise and interest. Everyone needs to be clear on
their own role and to be sure about what other team members do [11]. The multidiscipli-
nary foot care team should be available to assess outpatients with active foot disease, not
only in routine appointments but also in emergencies. Each team member should be avail-
able quickly in an emergency. There are, of course, other ways of organising care for
patients with diabetic foot problems, but the multidisciplinary, hospital-based, diabetic
foot clinic has proved to be a successful way of reducing amputations and improving out-
comes [12].
The specific personnel will vary according to the health care system and country. In this
paper, for convenience, reference is mainly made to the personnel of the multidisciplinary
diabetic foot clinic at King’s College Hospital, London. However, the specific principles of
care are universal and will need to be upheld by the particular personnel in different health
care systems.

26.4.1 Role of the Podiatrist

Podiatrists are the gatekeepers of the clinic, making initial assessments on both emergency
patients and those with planned appointments, before ensuring that appropriate members
of the multidisciplinary team jointly assess and treat the patient. The initial assessment has
three main aims:
●● To make an accurate diagnosis of the diabetic foot problem and start appropriate treat-
ment, for example, debridement and dressing of an ulcer. At King’s, the podiatrists
also undertake casting of the foot to offload ulcers and stabilise acute active Charcot
feet. In other clinics, this may be carried out by specially trained nurses or plaster
technicians.
●● To diagnose infection and then in conjunction with the multidisciplinary team to start
antibiotics and decide on the need for surgical debridement.
420 26 Setting up a Diabetic Foot Clinic

●● To perform an assessment of foot perfusion and if ischaemia is present to arrange vascu-

lar laboratory investigations, prior to review by the multidisciplinary team to consider
the necessity and mode of early revascularisation.
The podiatrists also have a role in educating the patients, usually on a one to one basis.
In other clinics, tissue viability nurses, vascular specialist nurses, or specialised wound
care nurses carry out similar roles to the podiatrist described above [13].

26.4.2 Role of the Diabetologist

Diabetologists play a special role in understanding, managing, and co-ordinating the care
of patients with diabetic foot problems. They are responsible for the diagnosis of infection
and ischaemia and facilitate prompt treatment of infection, as well as treating neuropathic
pain. They also decide which patients require urgent admission to hospital and are then
responsible for overseeing their care on the wards. The diabetologist is supported by medi-
cal colleagues who provide clinical assistance throughout the clinic’s weekly opening
hours. This expedites decision-making for admission, prescribing, referrals, and manage-
ment of diabetes and other medical problems. Patients requiring admission are usually
well-known to the inpatient team and follow-up in the diabetic foot clinic after discharge
also provides continuity of care to and from outpatient to the inpatient setting.

26.4.3 Role of the Nurse

Nurses have various roles in diabetic foot clinics. In some clinics, they perform much of the
wound care, dressing changes, and casting as described for the podiatrists above. At King’s,
the nurses manage and dress leg ulcers of diabetic patients that are referred to the clinic
despite it being a foot clinic, and also apply compression bandaging when appropriate.
They also liaise with the community health care system on behalf of all the patients who
attend the foot clinic to make arrangements for community nurse to visit patients who
need their foot ulcer or leg ulcer dressed at home.
Also, the nurses administer intravenous antibiotics and are responsible for inserting and
taking care of the peripherally inserted central catheters (PICC) lines through which these
drugs are given. They lead the home intravenous antibiotic programme for patients of the
foot clinic and liaise with community nurses. The nurses also provide a phlebotomy service
and thus save patients a journey to the main hospital phlebotomy clinic. The nurses also
monitor patients who are unwell during clinic and treat episodes of hypoglycaemia. In
some clinics, diabetic specialist nurses attend and advise patients on the management of
their diabetes.

26.4.4 Role of the Orthotist

The orthotist brings knowledge and understanding of pathology, biomechanics, and
engineering to the team with the aim to improve the function of the patient, from giving
simple advice on foot care and footwear to providing custom orthoses to improve weight
and pressure distribution by offloading areas of high pressure and supporting unstable
Charcot joints.
 26.4 ­Personnel for the Diabetic Foot Clini 421

26.4.5 Role of the Orthopaedic Surgeon

The orthopaedic surgeon takes part in regular joint multidisciplinary clinics and joint
orthopaedic ward rounds where specialist orthopaedic surgical input is required notably in
persistent or recurrent foot ulceration, osteomyelitis, and Charcot feet. In terms of surgical
activity, the orthopaedic surgeon is responsible for debriding infected neuropathic feet,
­correcting forefoot abnormalities, and reconstructing severely deformed Charcot feet.

26.4.6 Role of the Vascular Surgeon

The vascular surgeon takes part in the one-stop fast track joint vascular clinics in assessing
the patient, planning vascular investigations, reviewing results, and implementing treat-
ment – all in the same day. The surgeon also takes part in joint vascular ward rounds. The
surgical duties consist of arterial bypasses, including distal bypasses to the leg and foot
arteries and debriding ischaemic infected feet.

26.4.7 Role of the Plastic Surgeon

The plastic surgeon provides advice and expertise on all aspects of soft tissue deficits and
reconstructive surgery both in joint multidisciplinary clinics as well as on ward rounds.
The surgeon debrides neuropathic feet and carries out skin grafts and free tissue transfer.

26.4.8 Role of the Interventional Radiologist

The role of the interventional radiologist is a combination of providing advice and imple-
menting medical procedures. The radiologist leads a weekly multidisciplinary vascular
radiology meeting and is responsible for making joint decision with colleagues regarding
surgical vascular interventions. The radiologist also advises on and performs vascular
imaging, angioplasties, and stenting [9].

26.4.9 Role of the Vascular Scientist

The vascular scientist, working in the vascular laboratory, is important for assessing the
degree of ischaemia. With the development of high frequency transducers probes with
increased spatial resolution, Duplex ultrasonography allows visualisation of sites of arterial
disease from the iliac arteries downwards to the small pedal vessels in the feet [9]. Such
techniques are also useful to assess the response to endovascular revascularisation. The
scientists also carry out a formal surveillance programme of open bypass interventions
with assessments made for one year, post bypass, to detect any critical stenosis or occlusion,
which is then communicated urgently to the vascular surgeon.

26.4.10 Role of the Microbiologist

Microbiology input is essential for successful wound management and the microbiologist
attends the joint ward rounds. With the emergence of increasingly resistant organisms
422 26 Setting up a Diabetic Foot Clinic

grown from diabetic foot ulcers, rapid access to culture results is essential. In other health
care systems, the infectious disease specialist has an important similar role.

26.4.11 Role of the Pharmacist

A pharmacist with special responsibility for antibiotic dispensing attends the joint vascular
round and in conjunction with the microbiologist advises on the choice and dosage of
antibiotics.

26.4.12 Role of the Physiotherapist and Occupational Therapist

A physiotherapist attends the joint orthopaedic clinics to advise patients on safe and opti-
mum immobilisation for pressure relief and also to supervise rehabilitation and gradual
mobilisation when patients come out of casts.
All patients admitted to the ward are assessed by physiotherapists and occupational ther-
apists who advise on non-weight bearing techniques and tasks of daily living both pre- and
postoperatively and also on discharge from the hospital.

26.4.13 Role of the Dermatologist

The foot clinic has ready access to the dermatology department and patients with dermato-
logical problems such as possible malignancies and inflammatory dermatoses are seen on
the same day by dermatologists visiting the foot clinic.

26.4.14 Role of the Psychiatrist

The foot clinic has access to the liaison psychiatry service, which provides patients with
psychological and psychiatric care as part of their overall management of their diabetes.

26.5 ­Organisation of the Diabetic Foot Clinic

Overall, the diabetic foot clinic should be set up so that it can take on the role of an ‘opera-
tions centre’ or a ‘command centre’ for diabetic foot problems. The diabetic foot clinic
should be the focus of all referrals of patients with diabetic foot problems from the sur-
rounding area and if needed, from afar. In setting up a diabetic foot clinic, it is necessary to
organise the clinic in such a manner to ensure that certain core functions are carried out by
the members of the diabetic foot team to satisfy the basic principles of care. There should
be the facility to see patients urgently through an open access to the clinic. The use of
­modern imaging is important in diagnosis and the foot clinic can facilitate urgent visits to
radiology, nuclear medicine, ultrasound departments, and vascular laboratory. The clinic
can facilitate urgent measurement of inflammatory parameters, such as serum C-reactive
protein. The clinic should provide an opportunity for health care professionals to see
patients together in multidisciplinary specialist joint clinics. In these specialist clinics, it is
possible to organise a ‘fast-track’ service in a ‘one-stop’ visit, comprising clinical ­assessment,
 26.5 ­Organisation of the Diabetic Foot Clini 423

same day investigations and urgent treatment. In order to carry this out, the patient may
need to be present throughout the day and the diabetic foot clinic will act as a multidisci-
plinary diabetic foot day unit [14].

26.5.1 Treating Emergency Patients with Open Access to the Clinic

Diabetic foot patients undergo repeated crises, often starting with minor trauma, aggra-
vated by neuropathy and/or ischaemia, and accelerated by the swift onset of infection. The
diabetic foot can rapidly develop significant tissue necrosis or foot deformity and become a
limb and also a life threatening emergency. One of the key requirements of a modern dia-
betic foot service is the capability to offer patients rapid access to the multidisciplinary
team before reversible tissue damage progresses to necrosis [15]. Thus, an important aspect
of the organisation is an open access service which should operate throughout office hours
of the clinic, and in which patients can be seen without a prior booked appointment, hav-
ing been referred either by themselves or by their community podiatrist, nurse, or general
practitioner. Comprehensive multidisciplinary interventions should be instigated within
hours instead of weeks [6, 7]. Outside office hours, special arrangements can be made with
the emergency department of the hospital to accept and treat patients with urgent diabetic
foot problems.
The UK National Diabetic Foot Audit has recently stressed that the longer the time it
took for a patient with a new diabetic foot ulcer to reach expert care, the greater the chance
of the ulcer being severe and being unhealed after six months [16]. Those with severe ulcers
at first expert assessment were more likely to have a hospital admission within six months,
and to have admissions involving foot disease, revascularisation, and amputation, than
people with less severe ulcers [17]. National guidelinesfrom the UK indicate that diabetic
foot care emergencies should be referred immediately to a multidisciplinary foot care team
[18].This includes patients in whom overwhelming infection or ischaemia is ‘attacking’ the
foot and leading to significant necrosis in a ‘diabetic foot attack’. Such patients need rapid
treatment and admission to hospital through the open access service provided by the
­diabetic foot clinic.

26.5.2 Organisation of the Clinic Including Joint Specialist Clinics

Day to day multidisciplinary treatment is carried out by podiatrist, nurse, and diabetologist.
An important treatment for neuropathic ulcers is offloading. At King’s, casting is carried
out by the podiatrists who construct total contact casts, bi-valve plaster casts, and
Scotchcasts™ in the foot clinic. An orthotic service is available in treatment rooms adjacent
to the diabetic foot clinic providing same-day access to orthotic facilities, stock shoes, cus-
tom footwear, temporary pressure relief, and immobilisation devices.
An important development in managing the increasing complexity of diabetic ischaemic
and neuropathic foot problems has been the development of joint multidisciplinary clinics.
All members of the team must realise that truly multidisciplinary management can only be
achieved by holding regular joint clinics where appropriate groups of patients are collected,
and specialists work together in an environment encouraging swift joint consultation and
co-treatment. Communication is important to allow the team to function well. Within
424 26 Setting up a Diabetic Foot Clinic

these specialist clinics, it is possible to organise a ‘fast-track’ service with a ‘one-stop’ visit.
These joint clinics are popular with the patients as they see all specialties at one visit. The
three main joint clinics are orthopaedic, vascular, and plastic surgery clinics.

26.5.3 Joint Orthopaedic Clinic

The joint orthopaedic clinic is attended by orthopaedic surgeon, podiatrist, and diabetolo-
gist. Patients with Charcot osteoarthropathy and patients needing complex deformity cor-
rections and limb reconstructions are seen. The neuropathic foot with persistent forefoot
ulceration or deformity is evaluated and patients are predominantly assessed for forefoot
reconstruction of toe deformities and for midfoot and hindfoot reconstruction of Charcot
osteoarthropathy. A decision is reached to pursue either surgical treatment or conservative
management. If the latter, then a total contact cast is applied the same day and the patient
is followed up in special casting clinics. A number of patients with Charcot foot deformity
have peripheral vascular disease and are seen jointly by the vascular, orthopaedic, and dia-
betes teams, which further integrates their overall care. Occasionally inpatients, who are
undergoing orthopaedic reconstruction, also need revascularisation surgery, and both
operations are performed during the same admission.

26.5.4 Joint Vascular Clinic

Modern diabetic foot care has been transformed by the multidisciplinary diabetic foot team
with the vascular surgeon and diabetologist liaising closely, together with the podiatrist and
other members of the team. The joint vascular clinic allows expert evaluation of the diabetic
ischaemic foot with same day Duplex assessment in the vascular laboratory in a fast-track
‘one stop’ approach to facilitate an early decision regarding revascularisation [9]. The need for
angiography can be rapidly agreed upon and either angioplasty as a day case when possible
or bypass surgery can be promptly carried out. It has been reported that a delay of more than
two weeks from referral to revascularization is as an independent risk factor for major limb
amputation in patients with diabetic foot ulceration [19]. Ischaemic patients are followed up
post operatively in the diabetic foot clinic to provide continuity of care for wounds and ampu-
tation sites. Follow up includes routine preventive foot care, to detect problems early, rapid
and aggressive care of ulcers, and the provision of statins and aspirin for secondary preven-
tion of arterial disease. Vascular scientists working in the vascular laboratory carry out non-
invasive Doppler ultrasonography imaging and conduct a surveillance system for arterial
lower limb bypass grafts, informing the vascular surgeons of any critical graft stenoses.

26.5.5 The Multidisciplinary Vascular Radiology Meeting

The multidisciplinary vascular radiology meeting is attended by interventional radiologists
as well as by vascular surgeons, vascular scientists, and diabetologists. One of the team of
interventional radiologists leads the meeting. Each case is presented by the appropriate
clinician, haemodynamic vascular data are reviewed and then imaging is discussed. There
is a review of all the previous week’s imaging including Duplex sonography, CT and MR
angiograms and joint decisions are made as to the suitability of angioplasty or alternatively
 26.5 ­Organisation of the Diabetic Foot Clini 425

arterial bypass after careful review of the patient’s co-morbidities. The radiologists carry
out both routine and emergency procedures in 3 interventional suites with a 10-bedded
interventional day case and recovery unit staffed by dedicated radiology specialist nurses.
They also provide an on-call interventional radiology service.

26.5.6 Joint Plastic Clinic

This is attended by plastic surgeon, podiatrist, and diabetologist. Patients with non-healing
ulcers and wounds are assessed and advice is given regarding soft tissue reconstruction.
Negative pressure therapy is useful in post-operative wounds [20]. In cases of severe tissue
destruction, surgical techniques, such as free flaps, are useful in restoring tissue loss.

26.5.7 Outpatient Parenteral Antibiotic Therapy (OPAT)

The diabetic foot clinic has incorporated the opportunities offered by the delivery of intra-
venous antibiotics in the community. Whilst it sometimes allows admission avoidance, it
regularly facilitates early discharge from hospital and it is the patient’s choice over hospital
confinement. The OPAT programme is coordinated by foot clinic nurses and supervised by
the medical team. PICC lines are the main route of intravenous access, both at home and
in hospital. The site of insertion of PICC lines in the antecubital fossa requires regular
skilled care and maintenance. Patients undergoing home intravenous antibiotic therapy
are seen usually once weekly in the clinic.

26.5.8 In-Patient Care

When diabetic patients with severe foot problems are admitted to hospital, they should be
looked after by the multidisciplinary team, which attends the diabetic foot clinic. Some
patients may be under the primary care of the vascular or orthopaedic surgeons and others
under the care of the diabetologist. However, there should be joint ward rounds and multi-
disciplinary team meetings. This has been facilitated at King’s College Hospital by the crea-
tion of the post of diabetic foot practitioner, who, as an experienced podiatrist, coordinates
all aspects of inpatient care including, wound, microbiology, mechanical, vascular and
metabolic aspects and is particularly skilled in applying negative wound pressure therapy
[20]. Diabetic foot practitioners constantly review the inpatients and this serves as an ‘early
warning system’ for the deteriorating diabetic foot, resulting in immediate discussion with
the diabetic, vascular, orthopaedic, and plastic surgical teams. In other health care systems,
nurse practitioners take on these roles.

26.5.9 Reception of Patients and Administration

It is important to have a sympathetic and efficient reception service which is crucial for the
running of the open access clinic. The reception staff are the first point of contact in the clinic
for patients who may be very anxious. Administrative and clerical support is essential to record
and analyse performance [21]. For foot clinics situated in hospitals, it is important to work
closely and harmoniously with hospital managers to achieve optimum economic efficiency.
426 26 Setting up a Diabetic Foot Clinic

26.5.10 Leadership
The leader must be passionate about the care of the diabetic foot and be able to motivate
and encourage patients and health care professionals, acting as a ‘local champion’ for dia-
betic foot care [22]. The leader must be able to drive the work of the clinic and recruit and
retain staff. Different disciplines may be best positioned to take on leadership roles but
enthusiasm and belief in the importance of diabetic foot care is the overriding prerequisite
to lead the diabetic foot clinic team. [8], [11]. In the presence of increasing financial pres-
sure of recent years, members of the diabetic foot clinic and especially the leader should
work closely with hospital managers in the development and successful completion of
business plans to maintain the financial integrity of the clinic.

26.5.11 Activities Other than Patient Care in the Diabetic Foot Clinic
This chapter has concentrated on the clinical aspects of diabetic foot care. In addition to
this and according to resources, diabetic foot clinics should teach patients, health care pro-
fessionals, and the public about the best care of the diabetic foot by arranging seminars for
both professionals and patients and training courses for all disciplines. Again, according to
the circumstances and resources of the clinic, members may also research into the causes
of and devise new treatments for diabetes associated foot complications.

26.6 ­Conclusion

The natural history of the diabetic foot is rapid and aggressive. The diabetic foot clinic must
be set up to offer a rapid and open access service, early diagnosis and urgent treatment
using a multidisciplinary approach to get the right specialists in the room, at the right time,
working together with the patient at the centre. The diabetic foot and its progression may
seem difficult and complex but it is not an impossible condition, and with abundant energy,
skill, patience, enthusiasm, and coordination of expert multidisciplinary treatment, sur-
prisingly good results can be achieved.

­References

1 Ndip, A. and Jude, E.B. (2009). Emerging evidence for neuroischemic diabetic foot ulcers:
model of care and how to adapt practice. Int. J. Low. Extrem. Wounds 8: 82–94.
2 Armstrong, D.G., Cohen, K., Courric, S. et al. (2011). Diabetic foot ulcers and vascular
insufficiency: our population has changed, but our methods have not. J. Diabetes Sci.
Technol. 5: 1591–1595.
3 Jeffcoate, W.J., Chipchase, S.Y., Ince, P. et al. (2006). Assessing the outcome of the
management of diabetic foot ulcers using ulcer-related and person-related measures.
Diabetes Care 29: 1784–1787.
4 Prompers, L., Huijberts, M., Apelqvist, J. et al. (2007). High prevalence of ischaemia,
infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline
results from the Eurodiale study. Diabetologia 50: 18–25.
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5 Gershater, M.A., Löndahl, M., Nyberg, P. et al. (2009). Complexity of factors related to
outcome of neuropathic and neuroischaemic/ ischaemic diabetic foot ulcers: a cohort
study. Diabetologia 52: 398–407.
6 Driver, V.R., Madsen, J., and Goodman, R.A. (2005). Reducing amputation rates in patients
with diabetes at a military medical center: the limb preservation service model. Diabetes
Care 28: 248–253.
7 Driver, V.R., Fabbi, M., Lavery, L.A., and Gibbons, G. (2010). The costs of diabetic foot:
the economic case for the limb salvage team. J. Am. Podiatr. Med. Assoc. 100: 335–341.
8 Neville, R.F. and Kayssi, A. (2017). Blood purification review – advances in CKD 2017
development of a limb-preservation program. Blood Purif. 43: 218–225. https://doi.
org/10.1159/000452746.
9 Huang, D.Y., Wilkins, C.J., Evans, D.R. et al. (2014). The diabetic foot: the importance of
coordinated care. Semin. Interv. Radiol. 31: 307–312.
10 Edmonds, M.E., Blundell, M.P., Morris, M.E. et al. (Aug 1986). Improved survival of the
diabetic foot: the role of a specialized foot clinic. Q. J. Med. 60: 763–771.
11 Piaggesi, A., Coppelli, A., Goretti, C. et al. (2014). Do you want to organize a multidisciplinary
diabetic foot clinic? We can hlelp. Int. J. Low. Extrem. Wounds 13: 363–370.
12 Sanders, L., Robbins, G., and Edmonds, M. (2010). History of the team approach to
amputation prevention: pioneers and milestones. J. Vasc. Surg. 52 (3 Suppl): 3S–16S.
13 Williams, D.T., Majeed, M.U., Shingler, G. et al. (2012). A diabetic foot service established
by a department of vascular surgery: an observational study. Ann. Vasc. Surg. 26: 700–706.
14 Manu, C.A., Edmonds, M. et al. (2014). Transformation of the multidisciplinary diabetic
foot clinic into a multidisciplinary diabetic foot day unit: results from a service evaluation.
Int. J. Low. Extrem. Wounds 13: 173–179.
15 Uccioli, L., Meloni, M., Giurato, L. et al. (2013). Emergency in diabetic foot. Emerg. Med. 3:
160. https://doi.org/10.4172/2165-7548.1000160.
16 National Diabetes Foot Care Audit - 2014-2016 (2017): https://digital.nhs.uk/catalogue/
PUB23525 (accessed Sept 5 2017).
17 National Diabetes Foot Care Audit (NDFA), Hospital Admissions Report 2014-2016 (2017).
18 National Institute for Health and Clinical Excellence (2015). Diabetic foot problems-
prevention and management. NICE Guidelines 19. www.nice.org.uk/guidance/ng19
(accessed 4.02.2018).
19 Noronen, K., Saarinen, E., Albäck, A., and Venermo, M. (2017). Analysis of the elective
treatment process for critical limb Ischaemia with tissue loss: diabetic patients require
rapid revascularisation. Eur. J. Vasc. Endovasc. Surg. 53: 206–213.
20 Apelqvist, J., Willy, C., Fagerdahl, A.M. et al. (2017). Document: negative pressure wound
therapy. J. Wound Care 26 (Sup3): S1–S154.
21 Paisey, R.B., Abbott, A., Levenson, R. et al. (2018). South-west cardiovascular strategic
clinical network peer diabetic foot service review team. Diabetes-related major lower limb
amputation incidence is strongly related to diabetic foot service provision and improves
with enhancement of services: peer review of the south-west of England. Diabet. Med. 35:
53–62.
22 Van Acker, K. (2014). Establishing a multidisciplinary/interdisciplinary diabetic foot clinic.
In: Contemporary Management of the Diabetic Foot (ed. S. Pendsey), 191–198. New Delhi:
Jaypee Medical Brothers Ltd.
 429

27

National Audit of Diabetic Foot Care

Continuing Audit Is Essential for the Delivery of Optimal Care
of Diabetic Foot Ulcers
William Jeffcoate1, Gerry Rayman2, and Bob Young3
1
Nottingham University Hospitals Trust, Nottingham, UK
2
The Diabetes Centre, Ipswich Hospital, Ipswich, UK; University of East Anglia, Norwich, UK and University of Suffolk, Ipswich UK
3
Diabetes UK, London, UK

Measuring the Effectiveness of the Management of Diabetic Foot Ulcers.

27.1 ­Why Should We Document the Outcome

of Routine Care?

Those who work in the field of the diabetic foot are confronted by repeated human ­disasters
on most days. The vast majority are deeply concerned and do the very best they can to heal
the ulcer, to save the foot, and to look after the person. But decisions regarding care are
made difficult by the lack of good treatment for many of the problems that they tackle – with
the only exceptions being the availability of antibiotics for infection and the provision of
good off‐loading when needed. Moreover, the drawn‐out nature of healing is such that it
can be very difficult for clinicians to judge just how well they are doing their job. And while
they are reassured by the knowledge that they are working hard, by seeing that colleagues
do nothing different and by the gratitude expressed by patients and relatives, they don’t
really know whether they are providing the best care possible.
And yet some – whether clinician or manager, and in general or specialist practice, physi-
cian, podiatrist, or surgeon – cannot be doing their job very well because there is evidence
of quite considerable variation in outcome, even within the same country. The incidence of
major amputation, for example, has been reported to vary eightfold across the USA [1] and
very recent data from England have revealed sevenfold variation in major amputation rates
between localities (clinical commission groups, CCGs) even after adjustment for age and
ethnicity [2]. Such variation is now well‐recognised by those who work in the field and
some may have become numb to the knowledge, but to anyone outside – not least those
who have a foot ulcer themselves or care for someone who has one ‐ such wide variation is
potentially shocking. Many would conclude that such variation means that a sizeable

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
430 27 National Audit of Diabetic Foot Care

minority of those responsible for either organising or delivering care of the diabetic foot are
seriously underperforming. And if this is the case, it follows that the investment into the
service, and/or the training and professionalism of clinicians is insufficient to ensure
equality of service for all who need it. For such a situation to persist would be intolerable in
any condition with a higher profile.
The key to reducing variation is to undertake systematic measurement of the services
available for people with diabetic foot disease, and to compare performance. The aim is not
to challenge the professionalism of individual clinicians but rather to learn from the ser-
vices and localities which aspects of the organisation and delivery of care are associated
with better outcomes. It then becomes possible to recommend more widespread adoption
of these practices. If the performance of the worst performing care services in UK was
improved to be no worse than the current median, then the incidence of limb loss for dia-
betes in England would be reduced by one third.

27.2 ­General Principles of Clinical Audit

Clinical audit is a three‐stage process which involves (i) measuring an aspect of clinical
performance, (ii) introducing a change in order to improve it, and (iii) repeating the meas-
urement to determine if the change has had the intended result. When repeated the process
can become the basis of a recurring cycle of improvement.

27.2.1 Choice of Outcome Measures for Clinical Audit of Foot Care

in Diabetes
Outcome measures fall into two groups: (i) those that are based on data that are already
being captured and (ii) those that require new data to be collected. Distinction between
these is central to the planning of systematic audit because an audit that requires the
­collection of new data will impose an extra burden on administrative and clinical staff who
may already be over‐worked, and this must obviously be kept to an absolute minimum. If
it is hard to complete data capture forms, many will not be completed or will not be com-
pleted as accurately as they should be:
i) Data already being captured
Data on amputation
The details that are most often collected are those relating to amputation. And while
amputation data are collected with relative reliability, their analysis requires consider-
able care. Three potential weaknesses have to be borne in mind:

a) Major (above ankle) amputations are essentially different from minor amputations
because they leave a person without a foot that they can walk on. The financial,
social and psychological consequences are enormous. It does not, therefore, make
any sense to combine the two into a single item: ‘lower extremity amputation’
(LEA) – except in an attempt to document the extent of in‐patient workload. It is
obvious that the incidence of major amputation is the more important of the two
 27.2 ­General Principles of Clinical Audi 431

types of operation but interpretation of data even on major amputation alone

­presents its own difficulties. These have been previously summarised [3].
b) Amputation is also not a measure of the natural history of the disease: it is a treat-
ment. Nevertheless, data on amputation form the basis of much of the literature on
the outcome of management of diabetic foot ulcers (DFUs) – which is in stark con-
trast to other conditions (such as all common cancers) in which treatment is never
used as the primary outcome measure. In addition, the decision to perform an
amputation depends not just on the severity of the condition but also on judgments
made about its relative benefit to the patient. Such judgments will inevitably be
influenced by the opinion of professional staff and it has been shown in one study
that the opinions of professional staff regarding the need for major amputation can
differ significantly [4].
c) The expression of data on amputation requires careful consideration of the denomi-
nator. In general terms, the denominator should be the total of those ‘at risk’ and this
is usually taken to be everyone in that community with known diabetes. In many
countries the prevalence of known diabetes is not systematically recorded even
though the numbers having treatments for hyperglycaemia may be – but these will,
of course, underestimate the total. Moreover, the prevalence of known diabetes is
increasing fast – not just because of changing lifestyle but also as a result of screening
programmes which result in many more cases being recognised before the disease
becomes overt. As such, the total will include more newly discovered cases and these
will often have lower mean blood sugar concentrations and a shorter disease dura-
tion, and hence be less likely to be affected by complications. In time, however, the
newly ascertained population will develop neuropathy and peripheral artery disease
(PAD) and will be at increasing risk of foot disease. It follows that the incidence of
major amputation may show a short‐term tendency to fall in countries which under-
take screening programmes but it is very likely to rise to new heights in 10–15 years.
Other hospital activity
Other routinely collected information includes data on hospital admission and
length of stay but both are difficult to align to an episode of foot disease with any
certainty. A foot ulcer may be coincidental to another illness but still contribute to
morbidity and length of stay. Data relating to rehabilitation following limb loss will
also give an incomplete picture because many people who have a leg removed never
actually walk again – either because of general frailty or because they die in the
post‐operative period.
ii) Newly recorded data
As previously discussed, it is imperative that the imposed burden of data capture must
be minimised and data entry must be easy to ensure that the information is reliable.
For example, information on the duration of diabetes can be difficult to determine in a
specialist clinic because it is often not recorded in the secondary care case notes and
many patients will themselves be unable to remember. Another item that can waste a
considerable amount of time is a question which asks how long an ulcer has been pre-
sent. While the question is sensible and the information of potential value, it is a detail
which patients do not always recall with precision and this will undermine the accu-
racy of the database.
432 27 National Audit of Diabetic Foot Care

The most important principle of data collection is that the total number of questions
asked should be reduced to an absolute minimum of essential items. People devising
such questions should resist the temptation to include those which fall into the
‘Wouldn’t it also be interesting to know if…’.category. The answer is that while it would
be interesting to know, such extra questions would be better reserved for another occa-
sion. Datasets can be changed: once one issue has been addressed it can be replaced
with another.

27.2.2 Definition of the Population

If outcomes are going to be compared between populations (of either people or ulcers), it is
important to determine the extent to which the populations are comparable. If the audit is
designed to look at some aspect of ulcer onset or outcome in a population of people with
diabetes, then it is important to define age, sex, ethnicity, social deprivation, type and dura-
tion of diabetes of the population because all of these are routinely recorded in at least
primary care records and all are independently linked to ulcer onset. Other factors, such as
the presence of PAD, can also contribute to ulcer onset and outcome. There is, however, no
agreement on the best criteria for defining or excluding clinically significant PAD in ­routine
practice and hence none that can be used in the audit of large numbers without introducing
some degree of uncertainty. Specialist bedside techniques to define PAD are only marginally
more useful than routine clinical methods and are time‐consuming and impractical in any
audit undertaken on a relatively unselected population.
If, however, the aim of the eventual comparison is to compare outcomes in comparable
types of ulcer, then the ulcer type needs to be defined. The Wagner classification is gener-
ally regarded as being outmoded and the most widely used is the University of Texas (UT)
system [5]. This system does, however, lack one particular component which is closely
linked to the time to ulcer healing, and that is a measure of area. The PEDIS [6] system is
similar to the UT classification but includes a measure of area – even though this system
was devised for the purpose of prospective research (where specific tests can be performed
on participants), and not for audit. The final classification which has been proposed for the
categorisation of DFUs and which was specifically devised for the purpose of audit (i.e. for
the study of populations rather than for the characterisation of individual ulcers) is the
SINBAD system. It is quick to do and has been validated in a number of widely differing
populations [7].

27.2.3 Choice of Outcome Measure

This subject has been described in detail elsewhere [8].

27.2.3.1 Healing
An important aim is obviously to document some aspect of ulcer healing – whether it is a
measure of change in the ulcer area or the percentage in a population which heal by a fixed
time point (such as by 12, 20, or 24 weeks). This approach requires the selection of a single
ulcer as an ‘index ulcer’. In general, however, an outcome measure should be ‘person‐­
centred’ rather than ‘ulcer‐centred’ and the results of the two can be quite markedly
 27.3 ­National Diabetes Foot Care Audit of England and Wale 433

­ ifferent [9]. There are a number of options that might be considered and these include
d
‘being alive and ulcer‐free’ at a fixed time point (such as 12, 20, or 24 weeks) and total ulcer‐
free days (with/without amputation) by one of the same fixed time points. The last has the
advantage of being not just a measure of time to healing but also of recurrence (new ulcera-
tion) (see below).

27.2.3.2 Onset of New Ulceration

The incidence of new ulceration after healing of another ulcer (including either recurrence
of the original ulcer or the development of an ulcer at another site) has been shown to be
in the region of 40 and 60% at one and three years, respectively. It is for this reason that it
is now emphasised that healing of a DFU should be regarded as the condition going ‘into
remission’ rather than being ‘cured’. To that end the use of ulcer‐free days (or months) has
become a very appropriate outcome measure for determining the effectiveness of an inter-
vention in the longer term.

27.2.4 Closing the Loop

The final component of audit is the need to introduce changes into the care pathway and to
monitor its effect. If, for example, it was shown that the incidence of major amputation was
particularly high in an area that had no specialist multidisciplinary team, then the logical
step would be to introduce such a team and to monitor the effect, as has been done in the
past by a number of centres – not all of which have been published but which include
Ipswich and Middlesbrough in UK [10, 11].

27.3 ­National Diabetes Foot Care Audit of England

and Wales

The National Diabetes Foot Care Audit of England and Wales (NDFA) [12] was launched in
2014, and is one of a family of audits linked to the National Diabetes Audit (NDA) [13]. The
core NDA database currently holds the demographic and disease details of over 98% of all
people in England and Wales with diabetes, derived from annual electronic download from
their GP records and hospital specialist diabetes records, hospital episode statistics and the
Office of National Statistics. These details can be linked to the information derived from the
specialist audits – which include the NDFA – using the unique NHS number of each person
in UK. This linkage means that basic data (such as age, sex, ethnicity, diabetes type and
duration, social deprivation, HbA1c, BP, smoking status, and complications) do not need to
be re‐entered for each DFU episode. All these data are held under tight electronic security
by NHS Digital [14]. Data collection for the NDFA initially required signed informed con-
sent from each patient but this requirement was removed in England (although not in
Wales) in August 2017 when participation in the audit became a formal direction from the
NHS. Since August 2017 it has also been possible to link the NDFA results directly with
records of hospital admissions and in‐patient activity. Linkage with mortality data held by
the Office of National Statistics has been available since 2018, and linkage with the National
Registry held by the Royal College of Surgeons is planned.
434 27 National Audit of Diabetic Foot Care

27.3.1 Design of the NDFA

The design of the NDFA was based on the principles outlined above. It was also subjected
to a formal pilot with volunteer sites prior to country‐wide implementation. The capacity
for electronic linkage to the NDA made participation very much easier and has proved
central to its widespread adoption. The new data which needed to be collected fell into two
parts: (i) those on the structure of foot care services which were sought from those respon-
sible for commissioning clinical services in each community and (ii) those that related to
each new foot ulcer episode and which were recorded by the specialist clinicians (whether
podiatrist, nurse, physician, surgeon, or other) who assumed care.

27.3.1.1 Structure of the Foot Care Pathway

The first part involve an annual questionnaire comprising just three questions on the struc-
ture of local care for the prevention and treatment of DFUs. These were sent each autumn
to the bodies responsible for the structure of health care provision in each area: Clinical
Commissioning Groups (CCGs) in England and Local Health Boards (LHBs) in Wales. The
three questions required a simple Yes/No reply and ask whether there is:
i) a training scheme designed to ensure that healthcare professionals have the necessary
competence to undertake routine foot examinations during annual diabetes reviews
ii) an established referral pathway to a designated foot protection service for people iden-
tified during annual foot examinations as being at increased risk, and
iii) an established referral pathway for patients with new, deteriorating or recurrent foot
disease to enable expert assessment within, when necessary, 24 hours.
It should be noted that these questions were simply designed to determine if an attempt
has been made to structure these services and not whether they have been adopted by all
care providers. Thus, the first required only that there was a training scheme in existence
and not that every person attended and actually had the necessary competence. The second
and third questions simply asked if there was a referral pathway and even though not every
person was necessarily referred in that way.

27.3.1.2 Baseline Clinic Details Documented at the Time of First Expert Assessment
The second part – the audit of process and outcome – is based on the ongoing collection of clinical
information on as many as possible of all newly occurring DFUs in England and Wales. The total
anticipated number is not known but is thought to be of the order of 60 000 [15]. The details
obtained from each new presentation relate to (i) the duration of the ulcer and (ii) the severity of
the ulcer (or of the selected index ulcer if there is more than one). Other baseline details (includ-
ing details of patient demographics and their diabetes) are derived by linkage to the parent NDA.
i) Ulcer duration at first expert assessment
In order to reduce the time that might be spent resolving uncertainties relating to defin-
ing ulcer duration, options are grouped into five categories (Table 27.1).
It is not usually possible for people to refer themselves for an expert consultation
­without a referral by their GP. However, some may refer themselves with a new episode
if they have previously been managed by the service or attend the same unit for routine
management of their diabetes. Others may be referred from another hospital team. All
are categorised as ‘self‐referred’ for the purpose of the audit.
 27.3 ­National Diabetes Foot Care Audit of England and Wale 435

Table 27.1 Options used for categorising the time

elapsed between presentation to any health care
professional and first expert assessment.

a) self‐referred
b) less than 2 days
c) 2 days but less than 2 weeks
d) 2 weeks but less than 2 months
e) more than 2 months

ii) Severity of the index ulcer at first expert assessment

Each new index ulcer is graded using the SINBAD system which does not require tests
other than those used in routine clinical assessment. Each of the features in Table 27.2
is graded No (not present, scoring 0) or Yes (present, scoring 1).
The total score for each ulcer will be between 0 and 6 and it has been shown in three
different continents that a score of 3 or more (designated ‘severe’) is associated with worse
outcome.

Table 27.2 The SINBAD classification and score for assessment of ulcer severity.

a. Site: On hindfoot No (0) or Yes (1)

b. Ischaemia: (lower limb arterial disease) No (0) or Yes (1)
c. Neuropathy: Present No (0) or Yes (1)
d. Bacterial infection: Present No (0) or Yes (1)
2 2
e. Area: Area <1 cm (0) or 1 cm or more (1)
d. Depth: To periosteum or joint capsule (0) To bone (1)

27.3.1.3 Clinical Outcome

A single patient‐centred outcome is used, with participating centres being asked to record
whether the affected person is alive and ulcer‐free (having neither an ulcer not any
unhealed surgical wound on either lower limb) at 12 weeks and at 24 weeks after first expert
assessment. If the person has had an amputation they are still recorded as being alive and
ulcer‐free if all operation wounds have healed. Other outcomes are determined from later
electronic linkage to hospital episode data (Hospital Episode Statistics, HES, in England or
Patient Episode Database for Wales, PEDW).

27.3.2 The Findings of the NDFA from 2014 to 2017

The full details of the preliminary findings of the NDFA, including baseline data and clini-
cal outcomes up to six months from presentation are available on line (NDFA 2014–2017
https://digital.nhs.uk/data‐and‐information/publications/statistical/national‐diabetes‐
footcare‐audit/national‐diabetes‐foot‐care‐audit‐2014‐2017 accessed 27th April 2018) and
have been published elsewhere [16].
436 27 National Audit of Diabetic Foot Care

27.3.2.1 Structure Audit

The findings from the structural audit were disappointing (even if not unexpected) with
less than 50% of CCGs/LHBs that answered all of the structure questions on at least one
occasion able to confirm that all three recommendations were in place. This result was
disappointing but almost certainly reflects the traditional lack of attention paid to the dia-
betic foot by both clinicians and non‐clinicians.

27.3.2.2 Process and Outcome

The findings from details of the total registered 22 653 ulcer episodes in 19 453 people were
that highly significant associations exist between the time elapsed from the first presenta-
tion of the ulcer to any health care professional and the time to first expert assessment and
both ulcer severity and clinical outcome. In this respect, ulcer outcome included both the
patient-centred outcome of being alive and ulcer‐free at 12 and 24 weeks as well as all rel-
evant outcomes derived from cross‐linkage with data from hospital episode statistics
(admissions, total lengths of hospital stay, and the numbers of both major and minor
amputations’). The implication is that shortening the time that elapses before first expert
assessment will result in an overall improvement in outcome, as previously suggested in a
number of single centre studies [10, 11, 17].

27.3.2.3 Variation
The NDFA has also confirmed the expected variation which exists between service provid-
ers in clinical outcome (whether survival without new ulceration or amputation) of both
less severe and severe ulcers. For example, the median figure for the incidence of being
alive and ulcer‐free at 12 weeks for people with severe ulcers was approximately 34% but
the values for individual providers (selected only by their registering 50 or more cases in
that category) ranged from approximately 13–49%.

27.3.2.4 Limitations of the NDFA Dataset

The NDFA has been very successful and has provided strong evidence to suggest that
certain aspects of the care process are closely associated with better or worse outcome.
As in any audit, however, it will be necessary to demonstrate that a change in practice
leads to improvement and the necessary quality improvement study is currently in the
planning stage.
The data themselves are, however, inevitably limited by population selection since it is
estimated that only 10–20% of all new ulcer episodes being identified up to March 2017.
Part of this will be the result of the inevitably slow start of a process which involves a
change in the working practice of potentially all specialist teams in the country, but part
will reflect the fact that a sizeable minority of centres do not have a specialist team and part
will reflect the fact that many DFUs – perhaps the majority – are managed exclusively in
the community [18].
The current analyses also do not distinguish between data from people registered for the
first time (whether or not it is their first episode) and those registered on two or more occa-
sions. Eventually, however, it is the aim to distinguish between those presenting with their
first‐ever ulcer and those suffering a repeat episode.
  ­Reference 437

27.3.2.5 From Audit to Guidance

It is hoped that the NDFA will provide the evidence that is needed to increase the adoption
of NICE guidance across England and Wales, with the aim that this will help minimise
variation and improve the overall outcome. Similarly, the results may provide new evi-
dence to suggest ways in which current best practice might also be made better.

27.3.3 Other Audit Initiatives

While this article has dwelt on the NDFA, it is still only one exercise and there are many more
that could, and should, be adopted in order to explore how care of DFUs may be improved.
One recent study of a rather smaller population in Norway has, for instance, also recently
reported a similar association between the time to first expert assessment and clinical out-
come [19]. There is nothing to stop individual centres, or groups of centres, launching their
own initiatives, as some have memorably done in the past [10, 11] and others have done much
more recently [17]. Diabetic Foot International [20] is planning multinational audit using a
common database, DIAFI, and thereby provide a facility especially for resource‐poor nations
in which diabetic foot disease presents a burden which is as great, if not greater, than in
industrialised nations. Given the difficulty of conducting randomised controlled trials in this
complex field [21], careful audit is likely to prove the mainstay of the evidence needed to
define optimal practice in this complex and challenging field for the foreseeable future.

­References

1 Margolis, D.J., Hoffstad, O., Nafash, J. et al. (2011). Location, location, location: geographic
clustering of lower extremity amputation among Medicare beneficiaries wuth diabetes.
Diabetes Care 34: 2363–2367.
2 https://fingertips.phe.org.uk/profile/diabetes‐ft (accessed Sept 5, 2017)
3 Jeffcoate, W.J. and van Houtum, W.H. (2004). Amputation as a marker of the quality of foot
care in diabetes. Diabetologia 47: 2051–2058.
4 Connelly, J., Airey, M., and Chell, S. (2001). Variation in clinical decision making is a partial
explanation for geographical variation in lower extremity amputation rates. Br. J. Surg. 88:
528–535.
5 Armstrong, D.G., Lavery, L.A., and Harkless, L.A. (1998). Validation of a diabetic wound
classification system. The contribution of depth, infection and ischemia to risk of
amputation. Diabetes Care 21: 855–859.
6 Schaper, N.C. (2004). Diabetic foot ulcer classification system for research purposes: a
progress report on criteria for including patients in research studies. Diabetes Metab. Res.
Rev. 20 (Suppl 1): S90–S95.
7 Ince, P., Abbas, Z.G., Lutale, J.K. et al. (2008). Use of the SINBAD classification and score in
comparing outcome of ulcer management on three continents. Diabetes Care 31: 964–967.
8 Jeffcoate, W.J., Bus, S.A., Game, F.L. et al. (2016). Reporting standards of studies and papers
on the prevention and management of foot ulkcers in diabetes: required details and markers
of good quality. Lancet Diabetes Endocrinol. 4: 781–788.
438 27 National Audit of Diabetic Foot Care

9 Jeffcoate, W.J., Chipchase, S.Y., Ince, P., and Game, F.L. (2006). Assessing outcome of the
management of diabetic foot ulcers using ulcer‐related and person‐related measures.
Diabetes Care 29: 1784–1787.
10 Krishnan, S., Nash, F., Baker, N. et al. (2008). Reduction in amputation over 11 years in a
defined UK population: benefits of multidisciplinary team work and continuous
prospective audit. Diabetes Care 31: 99–101.
11 Canavan, R.J., Unwin, N.C., Kelly, W.F., and Connolly, V.M. (2008). Diabetes‐ and
nondiabetes‐related lower extremity amputation before and after the introduction of better
organized foot care: continuous longitudinal monitoring using a standard method.
Diabetes Care 31: 459–463.
12 National Diabetes Foot Care Audit Third annual report (2018) www.hqip.org.uk/public/
cms/253/625/19/1084/ndfa‐3ar‐rep.pdf?realName=EfOm0U.pdf&v=0 (accessed 25th April 2018)
13 National Diabetes Audit (2016‐2017). (https://digital.nhs.uk/data‐and‐information/
clinical‐audits‐and‐registries/our‐clinical‐audits‐and‐registries/national‐diabetes‐audit
(accessed 25th April 2018)
14 https://digital.nhs.uk (accessed 13th May 2018)
15 Abbott, C.A., Carrington, A.L., Ashe, H. et al. (2002). The north‐west diabetes foot care
study: incidence of an drisk factors for new diabetic foot ulceration in a community‐based
cohort. Diabet. Med. 19: 377–384.
16 Jeffcoate, W., Yelland, A., Meace, C. et al. (submitted for publication 2018) Factor
associated with variation in the outcome of diabetic foot disease in England and Wales:
results of the National Diabetic Foot Care Audit (NDFA) 2014‐2017 Submitted to
Diabetologia
17 Paisey, R.B., Abbott, A., Leveson, R. et al. (2018). Diabetes related major lower limb
amputation incidence is strongly related to diabetic foot service provision and improves
with enhancement of services: peer review of the South‐West of England. Diabet. Med. 35:
53–62.
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rpatcice in the UK. Int. Wound J. 15: 43–52.
19 Smith‐Strøm, H., Iversen, M.M., Igland, J. et al. (2017). Severity and duration of diabetic
foot ulcer (DFU) before seeking care as predictors of healing time: a retrospective cohort
study. PLoS One 12 (5): e0177176. https://doi.org/10.1371/journal.pone.0177176.
20 http://www.d‐foot.org/d‐footinternational/diabetic‐foot‐international/(accessed 13th May
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21 Jeffcoate, W.J., Vileikyte, L., Boyko, E.J. et al. (2018). Current challenges and opportunities
in the prevention anf management of diabetic foot ulcers. Diabetes Care 41: 645–652.
 439

28

Regenerative Medicine and the Diabetic Foot

Zachary A. Stern-Buchbinder, Babak Hajhosseini, and Geoffrey C. Gurtner
Division of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA

28.1 ­Introduction

Currently 9.3% of the population in the United States carries a diagnosis of type 1 or type 2
diabetes and 35% of adults have impaired fasting glucose or are pre-diabetic [1]. These fig-
ures are expected to triple by the year 2050 [1–3]. Among the 30 million people in the
United States who suffer from diabetes [4], the prevalence of diabetic foot ulcers (DFUs) is
13% [5]. DFUs represent a major healthcare burden. Data from Medicare and private insur-
ers shows that DFUs cost the American healthcare system between $9–13 billion each year
[6]. The costs are high because (i) there are no therapies that are highly effective, and (ii)
diabetic wounds display a high rate of recidivism, with wounds recurring in up to 70% of
patients [7] (Figure 28.1). DFUs account in part for the high prevalence of lower extremity
wounds. In a national study of wound demographics in the United States evaluating data
from 68 wound centers across 26 states over the course of four years, there were 180 696
wounds treated in 59 953 patients, averaging three wounds per patient. Diabetic wounds,
along with venous leg ulcers and pressure ulcers constituted 48.8% of all wounds studied
[8] (Figure 28.2).
The incidence of lower leg amputation is eight times higher in diabetic than in nondia-
betic individuals [3, 9]. The five-year mortality for patients following amputation is approx-
imately 50% [3]. While interventions exist, such as offloading, local wound care, dressings,
growth factors, extracellular matrix (ECM), engineered skin, and negative pressure wound
therapy, many of these treatments are only moderately effective [2]. There is a pressing
need for new and more effective therapies.

28.2 ­Stem Cells

Stem cells are characterized by their capacity for self-renewal and differentiation. Though
they were first isolated from the hematopoietic system, stem cells have since been isolated
from other tissues including adipose tissue (e.g. adipose-derived mesenchymal stem cells

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
440 28 Regenerative Medicine and the Diabetic Foot

Figure 28.1 Diabetes is associated with impairments in wound healing. Repetitive stress coupled
with loss of protective sensation results in unnoticed injuries and fractures predisposing certain
predictable areas to increased pressure and tissue necrosis.

[ASCs]). Stem cells are often classified and subdivided by their relative potency, that is,
their power to differentiate into many different cell lineages. Pluripotent stem cells can be
induced to transform into any kind of cell of the body. By contrast, a stem cell that is self-
renewing but can only reproduce one kind of cell is said to be unipotent.
Scientists once believed that the potency of a stem cell lineage would decline ­irreversibly
over the course of embryonic development; however, it is now understood that terminally
differentiated cells can be ‘re-programmed’ to an embryonic-like state by promotion of cer-
tain key gene products [10]. Discovery of these induced pluripotent stem (iPS) cells has reori-
ented our view of stemness and the very concept of cell plasticity. In the right environment
and in the presence of select cell-differentiating factors, it may be possible to provoke a given
cell to transform into any other cell type found in the body. This would allow for replacement
of defective or deficient cells in myriad disease states, or even tissue-level engineering. A
patient’s own skin or blood cells might, for example, be induced to recapitulate a cell lineage
with known wound-healing properties. These autografted cells could be expanded and intro-
duced into a chronic, non-healing wound such as a DFU (Figure 28.3).
Stem cell populations persist in most adult tissues, providing limited regenerative poten-
tial over the course of life. It is these resident mesenchymal stem cells (MSCs) that allow
under normal circumstances for the healing of cutaneous wounds, for example. However,
the relative differentiation and loss of potency of these adult stem cells compared to embry-
onic or pluripotent stem cells explains in part why adults do not exhibit the scarless healing
observed during embryonic development of animals. Dormancy or absence of stem cells in
notoriously slow-healing tissues might explain why the central nervous system shows far
less capacity for healing and regeneration than does an organ such as the liver. On the other
hand, non-stem cells which are incapable of infinite self-renewal may provide only limited
tissue regeneration.
 28.2 ­Stem Cell 441

40000
Number of Wounds

30000

20000

10000

0
p m
yx
Fo g
ot
An e
O le
tto r
T s
Co high

Fin rm

Br ax
Isc ger

Sa Site
Ba m
Ha ck
Gr d
Pe in
Up Elb is
pe ow
Th Arm

He st
Pe Axilld
rin a
m
rea e
Bu the
ck
To

a
Le

Fo Kne

lv
Am hiu

ea
k

cru

eu
cc

or
r

r
we
Lo

Wound Location

Figure 28.2 DFUs are a major driver of the increasing number of wounds seen at specialized
centers [8]. Source: Jung K et al., Wound Repair Regen, 2016.

Clinical Surgery
Therapies

Processing

Bone

Muscle Cell Culture

Cartilage

Fat

Differentiation

Figure 28.3 ASCs in a reconstructive cycle. Stem cells can be harvested by liposuction, isolated, and
differentiated. They could then be autologously transplanted back into the patient. Source: Behr et al. [11].
442 28 Regenerative Medicine and the Diabetic Foot

Stem-cell therapies have generated tremendous excitement for their regenerative

c­ apacity, but significant challenges remain in understanding the mechanisms and full
capabilities of these cells [12]. While embryonic stem cells (ES) and iPS cells have the
­greatest plasticity, the existing immunogenic, tumorigenic, and ethical concerns limit their
clinical applicability. Adult derived MSCs have a more restricted plasticity that limits risk
of tumor formation, while maintaining the ability to differentiate into a wide variety of tis-
sue types [12, 13]. ASCs are an ideal source of MSCs due to their abundance and ease of
harvest [14]. Enzymatic digestion of adipocytes yields a remnant stromal vascular fraction
(SVF) comprising fibroblasts, vascular smooth muscle cells, and ASCs, among other cells.
ASCs constitute approximately 30% of the SVF [15]. ASCs can differentiate into bone, car-
tilage, muscle, and fat [16], consistent with a multipotent stem cell. Additionally, ASCs are
a potent source of cytokines known to promote tissue survival and angiogenesis [17]. The
combined properties of ASCs have led to a burgeoning field of translational work [18].

28.3 ­Diabetes and Healing Impairment

Normal wound healing involves the precise coordination of growth factors and chemokines
and cytokines. Hyperglycemia has been demonstrated to induce a variety of intracellular
changes. These include altered activity of nitric oxide, angiotensin II, transforming growth
factor beta (TGF-ß), and vascular endothelial growth factor (VEGF), abnormal lipid metabo-
lism leading to insulin resistance, and an increase in reactive oxygen intermediates [19–25].
Growth factors contribute to endogenous wound healing through the stimulation of wound
angiogenesis and re-epithelialization [26], pathways thought to be impaired in chronic
wounds [27, 28].
Hyperglycemia alters the microenvironment as well as local and circulating cells [29].
Diabetes causes molecular impairments in the skin through rapid degradation of hypoxia-
inducible factor 1 (HIF-1) that is responsible for synthesis of a wide range of growth factors
important for neovascularization and proliferation of local fibroblasts [30, 31]. Diabetes
also causes cellular dysfunction in circulating and local progenitor cells [32]. Importantly,
cells exposed to prolonged hyperglycemia display metabolic ‘memory’, where even upon
return to normoglycemic state, they do not regain their normal function [33, 34]. Thus,
although intensive glucose control reduces the risk of microvascular complications and
tissue comorbidities, it does not eliminate tissue dysfunction [35]. Topical replacement of
these progenitor cells on the diabetic wound would be a viable strategy to accelerate heal-
ing. This method has been successful in preclinical models [36–38].
Recent developments in single cell technology have made it possible to quantify cellular
heterogeneity [36, 39–42]. These techniques have been used to identify stem cell subsets in
human adipose tissue important for normal wound healing [36]. When enriched and
applied to murine diabetic wounds, these cell subsets improve diabetic healing [36].
Diabetic wounds comprise multiple cell types in addition to fibroblasts and ­keratinocytes.
Resident cells in the skin can respond to a variety of forces and are altered with changes in
the microenvironment as seen with hyperglycemia [30–32, 35]. In addition to adversely
affecting fibroblasts and keratinocytes, diabetes also causes cellular dysfunction in circulat-
ing and local progenitor cells [33, 34]. Specifically, there is reduced recruitment of diabetic
 28.4 ­Diabetes and Vascular Dysfunctio 443

(a)
Staining Control Healthy hASCs Diabetic hASCs
106 106 106

105 105 105

104 104 104

DPP4

103 103 103

102 102 102

101 101 101

100 100 100

100 101 102 103 104 105 100 101 102 103 104 105 100 101 102 103 104 105

CD55
(b) (c)
DPP4+/CD26+ hASCs (%)

40 * 50%
% total human EPCs

Controls
30 40%
Diabetics
30%
20
20% *
10
10%
0 0%
Healthy Diabetic *P<0.05

Figure 28.4 Diabetes causes the depletion of both circulating and local progenitor cells in patients
with type 2 diabetes [44]. A single-center clinical study in 130 patients with diabetes undergoing
bariatric surgery demonstrates a loss in a unique subset of adipose stem cells important for wound
healing. Rennert et al Nat Commun 2016 [36]. (c) A clinical study analyzing human circulating
progenitor cells demonstrates a depletion in endothelial progenitor cells in diabetes Tepper et al.,
Circulation 2002 [32].

bone marrow-derived mesenchymal progenitor cells (BM-MPCs) resulting in attenuated

neovascularization, which is irreversible even with tight glucose control [43]. Within this
larger BM-MPC population, there is selective depletion of two transcriptionally distinct
subpopulations in both type 1 and type 2 diabetes. These subpopulations have pro-vasculo-
genic expression profiles, suggesting that they are vascular progenitor cells. Thus, clinically
observed deficits in progenitor cells may be attributable to selective and irreversible tissue
damage in diabetes [43] (Figure 28.4).

28.4 ­Diabetes and Vascular Dysfunction

The greatest impact of diabetes is on the vascular system [45], and cardiovascular com­
plications are the most common cause of death in diabetic patients [45–47]. The main
­pathophysiologic mechanism underlying these complications seems to be dysfunctional
neovascularization in response to ischemia, as evidenced by the reduced growth of collateral
444 28 Regenerative Medicine and the Diabetic Foot

Angiogenesis Vasculogenesis

Blood Vessel Lumen Blood Vessel Lumen

Sprouting
Proliferation EPC
Recruitment
Proliferation
New Vessel Assembly
New Vessel
Parenchymal Parenchymal
Tissue Tissue HYPOXIA
HYPOXIA

Figure 28.5 Angiogenesis and vasculogenesis.

coronary vessels after acute myocardial infarction and the poor clinical outcomes associated
with diabetic peripheral arterial disease (PAD) as seen in the diabetic foot [48, 49].
This pathology involves a mix of structural and functional changes in blood vessel and
heart cellular architecture that is amplified by the limited regenerative capacity of these tis-
sues following insult. Traditional therapeutic modalities focusing on pharmacologic or sur-
gical intervention have shown only incremental benefits, as they do not address this crucial
regenerative deficiency [50]. Advances in stem cell research provide an alternative strategy
for the treatment of diabetes-associated vascular disease through tissue regeneration.
Discoveries in developmental biology implicate the vasculature as a key determinant for
both organ development and physiologic function [3, 4]. Since the vasculature plays a criti-
cal role as an inducer of cell differentiation and proliferation, early incorporation of a vas-
cular network into engineered tissues would appear to be essential. While tremendous
progress has been made in elucidating the mechanisms governing blood vessel growth and
vascular patterning, our understanding remains primitive [5–10, 12–17].
Neovascularization occurs by two distinct processes: angiogenesis and vasculogenesis
(Figure 28.5). In angiogenesis, signals are initiated that indicate a need for new blood vessels,
and mature resident endothelial cells proliferate and sprout new vessels. In contrast, during
vasculogenesis, circulating vascular stem cells (endothelial progenitor cells or EPCs) are mobi-
lized from the bone marrow (BM), a hypoxic environment, and form new vessels [51–56]. The
precise sequence and mechanism by which this process occurs remains poorly understood,
however, it is clear that vasculogenesis is of significant importance in response to ischemia
where it can account for 30–40% of new blood vessels formed [57]. It is also clear that aug-
menting the vasculogenic pathway can improve outcomes in diabetic animals [58].
Tissue regeneration via circulating progenitor cells requires two basic elements: a
functional progenitor cell subset (which can be thought of as the seed) and the appropri-
ate environment-specific signal production (which can be thought of as the soil). Thus,
the observed defects in vasculogenesis in diabetes may be due to defects in stem cell
number/function (seed), defects in the environment necessary for stem cell recruitment
(soil), or both.
 28.4 ­Diabetes and Vascular Dysfunctio 445

Neovascularization in response to ischemic injury occurs partially through vasculogen-

esis [59–61]. Strong evidence suggests that cells responsible for this process originate from
BM and travel to ischemic peripheral tissue to form new vessels [53, 55, 61–63]; however,
their specific lineage remains poorly understood. Hematopoietic stem cells (HSCs) and
MSCs are generally regarded as the most likely sources [55, 64, 65], although at present lit-
tle evidence exists to support the notion that HSCs can adopt non-hematopoietic fates [66–
69], and the case for MSCs rests primarily on their in vitro ability to differentiate into
endothelial cells and vascular smooth muscle [70–72]. Based on these findings, early clini-
cal trials using whole BM-derived cells have been performed with discordant results, likely
due to heterogeneity in this population [73–76]. Further characterization of these cells will
be required if they are to be used therapeutically.
MSCs, isolated based upon adherence to tissue culture plastic in vitro, have been
widely studied in their role as multi-lineage progenitors as they are easily obtainable
from subjects and readably expandable for use in bioengineering applications [77, 78].
However, MSCs are extremely heterogeneous in vitro and lack a definitive surface
marker (SM) profile that can be used in vivo for prospective isolation and analysis [53,
61, 79, 80]. Efforts to identify discrete MSC markers have lagged behind those focused
on HSCs [64, 72, 79, 81–83]. Several SMs have been associated with MSCs grown in
culture, but there is little consensus on which profile constitutes a ‘true’ MSC in vitro or
in vivo [84].
In spite of this, many groups have shown that BM-derived MSCs contribute to postna-
tal vasculogenesis [85–87], are mobilized to the circulation by hypoxia, and migrate
toward hypoxic stimuli in vitro [70, 88–90]. Evidence suggests that the progenitor cell
hypoxia response is blunted in diabetes. Decreased number and function of EPCs are
observed in diabetic patients using currently accepted marker profiles [32]. Yet little
work has been done to evaluate the effect of diabetes on MSCs. Recently, a candidate
BM-derived murine MSC population (Lin-/Sca-1+/CD45-) that responds to tissue
ischemia by increasing peripheral circulation was identified in vivo [91], an observation
not seen for HSCs (defined as Lin-/Sca-1+/cKit+ [LSK cells] [92]) using the same model
[91]. These cells express multiple ES cell genes, are mobilized into the circulation by
granulocyte-macrophage colony-stimulating factor (GM-CSF), and differentiate into
multiple tissue lineages under co-culture conditions [93, 94]. These findings suggest that
this may be an important vascular progenitor population, which could be linked to
impaired neovascularization in diabetes.
Advances in stem cell research may provide an alternative strategy for treatment of DFUs
through tissue regeneration, with target cell types such as endothelial cells and smooth
muscle cells [50, 95]. While a variety of stem and progenitor cells can differentiate into one
or all of these cell types including embryonic ES, iPS, bone marrow mononuclear cells
(BM-MNC), MSC, skeletal myoblasts, umbilical cord or peripheral blood cells, adipose tis-
sue-derived stem cells [96], EPC, and smooth muscle progenitor cells (SPC) [50], the most
effective cell type for regenerative therapy remains unclear.
Diabetic wounds are particularly hard to treat due to their multimodal pathology, yet
MSC-based therapies hold promise for their treatment due to potential delivery of both
regenerative cytokines and cells. Nonetheless, to successfully translate MSC-based therapies
to the clinical setting, a safe, reproducible cell source is needed.
 446 28 Regenerative Medicine and the Diabetic Foot

28.5 ­Functional Heterogeneity of Stem Cells

There is a growing understanding that stem cell lineages have tremendous intrinsic hetero-
geneity [97, 98]. Many stem cell populations have shown phenotypic heterogeneity follow-
ing clonal analyses or non-analytical sorting techniques [99–102], and even putatively
homogenous populations have shown significant diversity starting at the transcriptional
level [40]. In fact, the nature of heterogeneity within stem cells has been repeatedly empha-
sized by the basic science community as a key and yet unresolved question [81, 97, 98].
Heterogenous populations can be divided into subpopulations using single-cell tran-
scriptional analysis (Figure 28.6). Gene expression analyses are a crucial first step in defin-
ing cellular identity and function. Population-based transcriptional analyses, such as
microarray, are useful for defining aggregate gene expression, but cannot describe the tran-
scriptional program of individual cells within the group [103]. Analysis at the single cell
level is required to effectively define the transcriptional profiles of heterogeneous group of
cells, but this approach has been traditionally limited by technical restrictions and cost
[104, 105].
These single cell techniques have been used to study a putatively homogenous popula-
tion of murine long-term hematopoietic stem cells (LT-HSCs), and to identify multiple sub-
populations consistent with the known functional properties of these cells [40]. The
translational goal, however, is to isolate the identified sub-populations through fluores-
cence-activated cell sorting (FACS) for functional analyses and specialized therapeutic

Cell harvest /isolation Raw data acquisition

Bioinformatics
Primers data processing

Single cell FACS

(1 cell/well)

Reverse 1 2 3
Transcription

mRNA

Isolation of PCR
single cell mRNA
Microfluidic-based high-
Single cell cDNA throughput single cell qPCR Final data output

Figure 28.6 Schematic of microfluidics-based single cell transcriptional analysis. Cells are
isolated, FACS sorted as single cells into each well of a 96-well plate, and subjected to a low-cycle
pre-amplification reverse transcriptase polymerase chain reaction (PCR) to create complementary
DNA (cDNA) for each single cell across 48 gene targets. Single cell cDNA and primers for 48 genes
are loaded into the microfluidics chip, and 48 real-time PCR (qPCR) reactions are performed for
each of 48 cells simultaneously (2304 total reactions per chip). A novel bioinformatics analysis
quantifies the heterogeneity of each cell population and clusters the cells into subpopulations
based upon transcriptional activity.

0004670029.INDD 446 3/3/2020 7:43:04 PM

 28.6 ­Advances in Regenerative Therap 447

applications. To achieve this goal, Linear Discrimination Analysis (LDA) can be used to
identify a minimum number of ‘cluster-defining genes’, which can be used to screen SM
transcriptional activity for sub-population correlations using repeat microfluidic analyses.
Correlating SMs can then be used to isolate cellular sub-populations for functional analy-
ses [106].
ASCs have enormous clinical potential due to their abundance, multi-lineage poten-
tial, and regenerative paracrine profile [14, 17]. However, the ongoing use of incom-
pletely defined or heterogeneous ASC populations needs to be reoriented in order to
maximize their clinical potential [18, 107]. Initial attempts to identify human ASCs
(hASCs) sub-populations were limited by impure starting populations and/or the use of
assays evaluating binary expression of a limited number of protein markers using immu-
nostaining and cell sorting techniques [100, 101, 106]. A more thorough approach
requires the simultaneous quantitative analysis of single cells isolated from a well-
defined starting population for multiple transcriptional markers, with sufficient size
(number of cells and markers) to generate meaningful predictions about the origin of
cells and cell groups. Analyses of a tightly sorted population of hASCls reveals a sub-
population of cells with enhanced expression of specific stemness and vasculogenic-
associated transcription factors (Figure 28.7). Interestingly, this sub-population is also
associated with higher gene expression of specific cell SMs, enabling the isolation of this
sub-population for analysis of enhanced tissue regeneration capacities. The ability to
identify, isolate, and expand those stem cell subtypes which are most active in wound
healing and tissue regeneration will greatly enhance our ability to design new treat-
ments for the diabetic foot.

28.6 ­Advances in Regenerative Therapy

Regenerative therapies for the DFU must address the heightened inflammatory state
as well as the compromised neovascularization which together are the hallmarks of
this disease process. MSCs not only reduce inflammation by suppressing the inflam-
matory cytokines such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFNγ),
but also exert an antimicrobial effect either directly and/or by stimulating the phago-
cytic action of immune cells [108]. MSCs also have paracrine action within wound
tissue, secreting VEGF, SDF, and PDGF among other growth factors implicated in
angiogenesis [108]. In a randomized controlled trial of 24 patients with nonhealing
lower limb ulcers (DFUs and Buerger disease), those who received BM-derived MSC
treatment showed significant improvement in wound size and pain-free walking dis-
tance after 12 weeks [109].
It has been demonstrated in a mouse model of skin flap necrosis that ASCs enhance local
blood supply and promote flap survival. Researchers in this study observed a statistically
significant increase in capillary density following injection with ASCs, with some endothe-
lial cells staining positive for a fluorescent label borne by the stem cells [110]. In another
study, transplantation of autologous ASC-containing collagen matrix significantly acceler-
ated wound healing in diabetic mice [111]. In a study of 20 patients with PAD and chronic
ulcers of the lower limb, treatment with ASCs was associated with a reduction in both

0004670029.INDD 447 3/3/2020 7:43:04 PM

 448 28 Regenerative Medicine and the Diabetic Foot

High
Gene Expression
Low

Cluster 1 Cluster 2

Figure 28.7 Human adipose derived stem cell (hASC) clusters. Each small box represents a single
gene in a single cell, within individual cells in columns and genes in rows. Cluster 2 is largely
defined by high expression of genes related to stemness and vasculogenesis, with hypothesized
phenotypical implications.

diameter and depth of ulcers [112]. Raposio et al. studied 45 patients with chronic skin
ulcers, finding that 18 months of treatment with ASCs added to platelet-rich plasma (PRP)
significantly enhanced wound closure rates compared to standard wound care [113]. It has
been proposed that PRP might enhance the wound-healing ability of ASCs by releasing
growth factors such as PDGF-BB, VEGF, and EGF into the wound bed [114].

0004670029.INDD 448 3/3/2020 7:43:10 PM

  ­Reference 449

Bone marrow derived stem cells have also been used with some success. Thirty-seven
patients suffering from end stage- limb ischemia and diabetic foot for whom surgical
­revascularization and endovascular repair had already failed were selected for BM-MPC
treatment [115]. Following intramuscular (IM) injection with BM concentrate, 81% of
amputation-risk limbs were salvaged [115].
In order for MSCs to proliferate and stimulate the healing of DFUs, it is necessary to
design a delivery vehicle that will both ensure sustained cell release and offer some
­protection against the local environment which is highly inflammatory and laden with
proteolytic factors [116]. Materials that recapitulate the physiologic ECM using collagen,
elastin, or glycosaminoglycans (GAGs) are prime candidates [115].

28.7 ­Conclusion

New discoveries in the field of stem cell biology point toward the next frontier in treatment
of the diabetic foot. Preliminary results are promising, however more clinical trials in
human subjects are required to fully establish the efficacy and safety of these cell-based
therapies. There remains a great deal of work to be done in designing optimal formulations
and delivery vehicles which preserve or perhaps enhance the innate regenerative capacity
of these cell populations in the clinical setting. We may well be on the cusp of a new age in
the treatment of this highly morbid and exceedingly common pathology.

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29

Role of the Plastic Surgeon in Diabetic Foot Care

Joon Pio (Jp) Hong and Hyunsuk Peter Suh
Department of Plastic and Reconstructive Surgery, Asan Medical Center, University of Ulsan Collage of Medicine, Seoul, Korea

S
­ ynopsis

The treatment of non-healing diabetic foot ulcerations is complex, typically involving a

multidisciplinary team. Despite the efforts of the team, wound infection, and ischemia
often leads to limb amputation. This chapter introduces the role of plastic surgeons in the
multidisciplinary approach. Plastic surgeons bring on the capability to enhance healing by
soft tissue manipulation, following a reconstruction algorithm to manage and salvage dia-
betic foot ulcers (DFU). Having the reconstructive option in the treatment spectrum may
enhance the healing process and increase the chances for salvage.

29.1 ­Introduction

According to the statistics given in the US, approximately 3–4% of individuals with diabe-
tes mellitus (DM) currently have DFUs or deep infections, and up to 25% will develop foot
ulcers sometime during their life [1, 2]. The risk of lower leg amputation increases by a
factor of 8 once an ulcer develops, and the age-adjusted rate of lower extremity amputa-
tion in diabetic patients is 15-fold compared to patients without DM [3]. These chronic
difficult to heal DFUs negatively impact physical, emotional, and social quality of life, but
are also associated with a potentially huge economic burden to the family [4–6]. Patients
with diabetic foot pathology fear major lower extremity amputation more than death, foot
infection, or end stage renal disease (ESRD) [7]. Furthermore, the five-year mortality after
major amputations may range from 39% to as high as 80% [1, 8]. These are the reasons
why salvage for DFUs remains important as it may reduce economic burden, improve the
quality of life and perhaps reduce mortality. Plastic surgeons may play a critical role in
salvage of the limb as durable soft tissue coverage is essential. Soft tissue coverage in the
face of abnormal foot biomechanics (i.e. equinus, Charcot neuroarthropathy, hallux
­rigidus) may be doomed to failure, and consequently, a multidisciplinary is vital to ensure
optimal results.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
458 29 Role of the Plastic Surgeon in Diabetic Foot Care

29.2 ­Multidisciplinary Approach and the Spectrum of Care

The manifestation of diabetic foot disease may vary from an asymptomatic to critically
ischemic limb resulting in unavoidable amputation. The wide manifestation of signs and
symptoms is due to multifactor pathophysiology including ischemia, neuropathy, and
infection. The addition of external trauma, peripheral edema, and foot deformity may fur-
ther increase the risk for DFU [9]. These risk factors may act alone or synergistically to
result in Charcot deformities, Achilles tendon contractures, ulcerations, necrosis, and gan-
grene. One must consider these pathologies and manage them in sequence in order to
provide an efficient care for the foot. Failure to recognize the underlying factors will result
in early recurrence of foot wounds.
All of the team members, despite their specialty, need to see the patient as a whole.
Treatment for any diabetic foot problem must include optimizing glycemic control and nutri-
tional support, whilst aggressively managing the wound and/or infection to achieve closure
of the defect. Uncontrolled perioperative hyperglycemia should be avoided, since this will
significantly increase the complication rate after any reconstruction [10]. Evaluating the
patient’s nutritional status and correcting it accordingly prior to surgery is also very impor-
tant. Prealbumin with a half-life of two to three days is a good indicator for acute nutritional
status, and low values (<15 mg/dl) have been reported to be a risk factor for poor healing and
postoperative infection [11, 12]. Preoperative education is paramount for both the patient
and family, particularly with regard to postoperative care after the reconstruction.
Prior to embarking on major soft tissue reconstructive surgery, patients often receive
treatment from wound specialists and/or other specialty surgeons. Success after recon-
structive surgery depends on multiple variables such as general medical status, motivated
patient, adequate perfusion, eradication of infection (bone and soft tissue) and a prepared
wound bed [12]. Vascular surgery evaluation is warranted when the patient has diminished
or absent pulses, non-healing wounds and/or symptoms of critical limb ischemia. Diabetic
patients with peripheral neuropathy may not manifest the typical signs of claudication,
and a high degree of suspicion should be entertained in patients with poor healing.
Preparation of the wound bed is vital and includes debridement of nonviable or infected
tissue, local wound care, and appropriate offloading.
With the introduction of a multidisciplinary approach and improved technology, the
trend of management has shifted from major amputation to limb salvage [13]. Addressing
the issues of perfusion, infection, wound treatment, off-loading, bone surgery, and soft tis-
sue coverage, has resulted in increased limb salvage rates. The major amputation rate for
diabetic foot disease in our centre (3–4%) has declined significantly after instituting a mul-
tidisciplinary approach [14, 15]. Although major amputation is still required in select cases
(systemic sepsis, major tissue loss, significant comorbid factors, poor patient compliance,
and non-reconstructable peripheral vascular disease), the primary goal in patients with
diabetic foot disease is to achieve limb salvage by following a structure programme that
relies on good clinical judgement [16, 17]. Reconstruction of the diabetic foot involves
enhancing vascular status, maintaining function through understanding biomechanics
and providing soft tissue coverage. Plastic surgeons play a vital role in any successful limb
salvage programme, often working in concert with other surgical specialties to achieve
optimal results.
 29.3 ­Reconstruction Algorith 459

29.3 ­Reconstruction Algorithm

After the patient and the wound bed are stabilized, further evaluation of the wound is
made following the reconstructive algorithm as outlined in Figure 29.1. If the wound is
simple with minimal or no vital structures exposed, various options are available. If the
wound is large with healthy granulation tissue, skin grafting or a small local flap can be
performed [18]. Well granulating wounds indicate for good vascularity. The use of negative
pressure wound therapy often enhances granulation formation and can be used to prepare
the wound for reconstruction. However, if wound healing is stalling, then further vascular
evaluation is indicated.
The philosophy of reconstruction follows the principles of the reconstructive ladder,
using a step-ladder approach from simple to complex procedures to achieve wound heal-
ing. Although still valued and widely taught, this the concept of a wound-closure ladder
predates the era of modern reconstructive surgery [19]. The current thought process in
modern reconstructive surgery incorporates both soft tissue closure and foot function. For
example, a skin graft placed on a plantar defect will provide coverage, however a skin or
muscle flap with good padding and thicker skin will provide superior functional results.
Consequently, a simpler reconstructive option may not necessarily produce optimal and
durable soft tissue coverage. This is especially true for diabetic foot reconstruction, where
the consequences of inadequate coverage may lead to additional soft tissue loss, osteomy-
elitis, functional loss, increased medical cost, and even amputation. Thus, to provide opti-
mal results the reconstruction plan often migrate up and down the rungs of the ladder. An
evolved principle of the reconstructive ladder, the so called reconstructive elevator, requires
creative thoughts and considerations of multiple variables. Rather than a sequential climb
up the ladder, the elevator approach strives to achieve the best results by modifying the
approach as needed. (Figure 29.2) This paradigm of thought does not eliminate the concept

Hyperbaric
Oxygen
Negative
pressure
Cell Gene therapy
therapy therapy Growth
factor

Good standard of wound care

Systemic care Surgical options
Off loading
Nutrition Skin graft
Advanced dressings
Diabetes control Flap reconstruction
(Ideal wound environment)
Prevention Amputation
Infection control
Education
Vascular supply

Figure 29.1 The whole spectrum of treatment is shown. For anyone being part of the
multidisciplinary team, it is vital to understand the role and solutions of each member. From basic
management of blood sugar level to surgical solutions, the spectrum of treatment can be wide and
complex requiring a team approach.
460 29 Role of the Plastic Surgeon in Diabetic Foot Care

Diabetic Foot Defects no benefit

after debridement and infection control

Evaluate Vascular status

failure unreliable
reliable Bypass surgery
success Angioplasty
Conservative care
Simple wound Complex wound failure

Soft tissue reconstruction

Skin graft/Local flap failure
Bone reconstruction
NPWT Nerve decompression

failure

Amputation
Rehabilitation
Out patient Program

Figure 29.2 The reconstruction algorithm for diabetic foot. The key elements of the treatment are
shown from managing systemic condition, providing a good standard of wound care, evaluating/
enhancing vascular status, application of flaps for reconstruction and the follow-up afterwards.

of the reconstructive ladder, but rather recommends that the method of reconstruction be
chosen based on procedures that results in optimal function as well as appearance [20].

29.4 ­Debridement (this Is Covered in Detail

in another Chapter)

Understanding the vascular distribution of the foot, i.e. angiosomes, helps to plan not
only reconstruction but debridement [21]. When planning for reconstruction, one
should avoid violating the angiosome territory. Incisions and flaps that cross angiosomes
may lead to larger wounds and flap breakdown [22]. Planning debridement according to
the angiosome territory enhances flap survival by increasing the chance for marginal
vascularization from healthy surrounding angiosome territory [23]. There are six angi-
osomes of the foot and ankle originating from the three main arteries and their branches
to the foot and ankle. The three branches of the posterior tibial artery each supply dis-
tinct portions of the plantar foot. The calcaneal branch supplies the heel, the medial
plantar artery supplies the longitudinal arch (nonweight bearing portion of the medial
plantar foot), and the lateral plantar artery supplies the lateral midfoot and forefoot. The
two branches of the peroneal artery supply the anterolateral portion of the ankle and
hind foot. The anterior perforating branch supplies the lateral anterior upper ankle and
the calcaneal branch supplies the plantar heel. The anterior tibial artery and the con-
tinuous dorsalis pedis artery supplies the anterior ankle and the dorsum of the foot.
Fortunately, blood flow to the foot and ankle from the three vessels overlaps due to
 29.5 ­Evaluating and Enhancing the Vascular Statu 461

­ ultiple arterial–arterial connections [21, 24]. By selectively performing a Doppler

m
examination of these connections, it is possible to quickly map the existing vascular tree
and the direction of flow.

29.5 ­Evaluating and Enhancing the Vascular Status

In the reconstruction algorithm, all patients considered for microsurgical reconstruction

undergo a non-invasive CT-angiogram to evaluate the vascular status. Typically, there are
three types of wounds: neuropathic, ischemic, and neuroischemic. The neuropathic
wound may have a patent vessel but the distinction between neuropathic, ischemic, and
neuroischemic type is often not clear. Neuroischemic wounds are common, and the foot
and the extremity can show signs of arterial calcification, particularly in patients with
neuropathy and end stage renal disease. The CT-angiogram provides information regard-
ing general vascular anatomy and artherosclerosis in target vessels. This provides a road-
map to optimally choose recipient vessels and to properly select the flap donor site on the
foot or ankle. The overview is important as collateral vessels may be the main supply to
the distal limb. Without this information, one may elevate the flap harvesting the domi-
nant arterial source to the distal limb, causing limb ischemia. If the vascular status is in
doubt, then consultation for revascularization by angioplasty or bypass surgery is recom-
mended. Although preoperative angiograms may indicate intact anatomy of the artery to
the foot, actual findings upon surgery can be different. In order to confirm the distal
vascular flow, we use ultrasound duplex scans [12, 23]. Our recent experience shows that
peak blood flow velocity greater than 15–20 cm/s on the recipient vessels allows the flap
to safely survive [23]. After successful initial reconstruction using flaps, sudden ischemic
incident to the flap may be observed after one or two weeks. In cases of sudden re-­
occlusion of the artery an emergency angiogram is needed to evaluate the artery status
proximal to the anastomosis. The flap can be salvaged by additional angioplasty if early
intervention occurs. Currently, our initial approach is endovascular intervention due to
the simplicity and minimal invasiveness of the approach. We have observed an average of
6 to 12 cm/s velocity increase after angioplasty, increasing the adequacy of the recipient
artery for reliable flap take. Open bypass surgery is indicated when the endovascular
approach fails to restore the distal flow. In these cases, bypass surgery may not be enough
to salvage the foot, and the flap may require anastomosis to the bypass graft itself to sal-
vage the foot.
The optimal timing of when to perform reconstruction after vascular intervention is not
clear. Reports have shown successful free flap transfer with simultaneous vascular recon-
struction, however, early bypass failures within 30 days are reported to be high [25–27]. In
our experience, partial flap loss or total loss has occurred two to three weeks after combined
cases with simultaneous reconstruction or reconstruction a few days after vascular inter-
vention. This suggests that there should be a sufficient stabilization period after open vas-
cular intervention. For endovascular angioplasties, we usually approach the microsurgery
anastomosis after two to four days. This early approach maximizes the window of patent
flow after intervention and minimizes the risk involving re-occlusion of the artery proximal
to the anastomosis. Establishing adequate perfusion is essential prior to any reconstruction
462 29 Role of the Plastic Surgeon in Diabetic Foot Care

using skin grafts, local flaps and microsurgical reconstruction. If vascular intervention fails
in patients with open wounds and ischemia, amputation usually is required.

29.6 ­Skin Grafts and Substitutes

Autologous skin grafts are one of the most commonly used methods to provide coverage by
a plastic surgeon. The skin can be used as a full or partial thickness grafts and require a
recipient bed that is well vascularized and free of bacterial contamination [20]. The split-
thickness grafts are usually used as the first line of treatment in cases where wounds can-
not be closed primarily, or high tension is suspected on closure. A particularly high rate of
dehiscence may occur after forefoot amputation, largely due to the high tension during
closure. In these cases, skin grafting should be considered to facilitate closure. Skin grafts
should be avoided on wounds with exposed bone, poorly granulating beds, infection, tun-
nelling, and dead space. Autologous cultured keratinocytes can be used when split-thick-
ness donor sites are limited. However, the use of cultured epithelial autograft has been
hampered by reports that show it to be more susceptible to bacterial contamination, varia-
ble success rates, and is costly [28].
A skin substitute is defined as a naturally occurring or synthetic bioengineered prod-
uct that is used to replace the skin. They can used in a temporary, semi-permanent, or
permanent fashion [29]. Temporary epidermal replacements may be beneficial in
­superficial to mid-dermal depth wounds. In deeper wounds, dermal replacements are of
primary importance. Bioengineered products for superficial wounds include porcine
products such as EZ-derm and Mediskin (Brennen Medical-LLC, Saint Paul, Minnesota)
which helps to close the wound, decrease pain and improve rate of healing [29].
Biobrane (UDL Laboratories Inc., Rockford, Illinois) is a bilaminant skin substitute that
is used temporarily. The outer layer is formed with thin silicone payer with pores that
allow removal of exudates and penetration of antibiotics. The inner layer is composed
of three dimensional nylon filament weave impregnated with type I collagen to adhere
to the wound. Bioengineered products that are used for deep wounds are Allograft,
Alloderm (Life Cell Corporation, Woodlans, Texas), Integra (Integra Life Sciences,
Plainsboro, New Jersey), CGderm (CGbio, Seoul, Korea) and Apligraf (Organogenesis
Inc., Canton, Massachusetts). The gold standard for temporary skin coverage is cadaver
skin (allograft) which can used to cover extensive partial- and full-thickness wounds.
Allograft skin prevents tissue desiccation, decreases pain, insensible loss of water, elec-
trolytes and protein and suppresses the proliferation of bacteria [30, 31]. The acellular
dermal matrix engineered from banked, human cadaver skin can also provide single
stage reconstruction when used with a split-thickness skin graft [32]. Integra is an acel-
lular collagen matrix composed of type I bovine collagen cross-linked with chondroitin-
6-sulphate and covered by a thin silicone layer that serves as an epidermis [33]. It is
readily available and does not require a donor site, promoting granulation tissue and
decreasing metabolic demand on the patient. However, Integra must be used on clean
wounds and often requires a second stage for later skin grafting. This bilayer xenograft
can be used ­simultaneously with negative wound pressure therapy, potentially acceler-
ating the re-vascularization of the wound bed.
 29.7 ­Local Flap 463

The use of skin graft or skin substitutes facilitates closure in relatively well vascularized
bed and provide adequate coverage. However, if a large weight bearing portion needs cov-
erage, skin grafts, and dermal substitutes are less optimal as the reconstructed thin skin
will be likely to breakdown after weight bearing. This is particularly true on the plantar
aspect of the foot.

29.7 ­Local Flaps
Local flaps are usually used for smaller defects. Rotation, advancement (i.e. V–Y), ­bipedicle
flap, and transposition flaps are commonly used flaps based on the subdermal plexus or
the underlying vascular source without identification. These techniques are still widely
used for small or medium sized defects that can be reconstructed with regional skin.
Although local flaps are random pattern flaps based on the subdermal plexus, understand-
ing the angiosome as well as the perforator flap concept can increase the chance of success
[24]. When planning to use a local flap in the foot and ankle, a careful Doppler examina-
tion of the foot and ankle is important. When the flap is based on a perforator directly
entering the flap nourishing the subdermal plexus, it will ensure the viability. When per-
forators are visually identified and the flap is solely based on this perforator, it is defined
as perforator flap. Perforator flaps have evolved from musculocutaneous and fasciocuta-
neous flaps without the muscle or fascial carrier. It was a natural evolution as reconstruc-
tion needed fine tuning whilst aiming to minimize donor morbidities. The perforator flap
concept simplified reconstruction and overcame the applications and limits of classical
local flaps. By identifying the perforator as the pedicle and further dissecting towards the
source vessel, it allowed improved movement and better survival of flap. One form of per-
forator based local flap, the propeller flap, is an island flap that reaches the recipient site
through an axial rotation [34, 35]. When a perforator propeller flap is being elevated, the
perforator is dissected free from the fascial and fat adhesions to minimize the chance of
kinking. Although less rotation reduces the chance for kinking, the skin island may be
safely rotated up to 180°. Like the angiosome concept, one must understand the anatomy
and physiology of a single perforator territory to obtain the ideal design of the perforator
flap [36].
Another useful local flap for larger wounds on the foot is the keystone flap. Described by
Behan, the keystone flap is a curvilinear shaped trapezoidal design flap essentially being
two V–Y advancement flaps along the long axis of the flap [37]. The longitudinal tension of
the flap is released thus creating laxity and redundancy in the mid portion allowing to
move horizontally towards the defect with minimal tension. Because of the large size of
the flap, identification of the vascular source is not necessary and is presumed to have vari-
ous blood supplies from the perforators entering from the deep fascia. But when perfora-
tors are identified using a Doppler, one can also call this flap keystone design perforator
island flaps [37].
The reverse sural flap, medial plantar or lateral supramalleolar flaps can be used to
reconstruct moderate sized defects especially on the heel. However, caution is needed
as ischemic changes progress distally in the extremity, and the role of the subdermal
­circulation becomes more important. In these cases, reconstruction may lead to
464 29 Role of the Plastic Surgeon in Diabetic Foot Care

(a) (b)

Microvascular

Distant flap
Tissue expansion

Local flap Distant flap

Local flap
Skin graft
Skin graft

Direct closure Direct closure

Reconstructive ladder Reconstructive elevator

Figure 29.3 A simpler reconstructive option may not necessarily produce optimal results. The
‘reconstructive elevator’ concept chooses the most appropriate floor from which to choose our
reconstruction, based on the specific requirements of the patient, the wound and the circumstances.
Thus, to provide optimal form and function, we jump up and down the rungs of the ladder. The
reconstructive elevator requires creative thoughts and considerations of multiple variables to
achieve the best form and function rather than a sequential climb up the ladder.

s­ ubdermal circulation injury breakdown of the flap and surrounding skin. Thus, ade-
quate vascular evaluation of the foot may be warranted even in cases where local flaps
are planned.
Figure 29.3 shows a patient with DFU on the dorsum of the foot. After applying good
principle of care and with adequate circulation, the patient’s foot was reconstructed with a
propeller flap based on a perforator artery most likely from the dorsalis pedis artery. A
small skin graft was used to cover the donor site and the flap and donor site healed without
incident and achieved good overall contour.

29.8 ­Free Flaps

Historically, diabetic foot wounds have been regarded as a relative contraindication for
microsurgical free-tissue transfer to the lower extremity. This was due to the increased
incidence of small-vessel disease, resulting in impaired microcirculation. The thought
was that free tissue transfer to an impaired microcirculation was doomed to failure.
Particularly, it was believed that diabetic patients have both macro and micro arteriolar
occlusive disease contributing to ischemic lesions [38]. However, other studies have
failed to demonstrate increased arteriolar occlusive disease or endothelial proliferation
in small vessels branching from the main source [39–42]. A meta-analysis of 18 studies
of free tissue transfer in 528 patients suggests the indications for surgery are: (i) Lower
 29.8 ­Free Flap 465

limb defect which has not displayed any signs of granulation or healing despite adequate
debridement or necrotic tissue and conservative treatment; (ii) No significant renal func-
tion impairment; (iii) No significant systemic illness likely to be exacerbated by multiple
operations and prolong rehabilitation; (iv) Previously ambulatory status with the aim to
restore a functional limb; (v) Patients who are likely to engage in the significant
­physiotherapy required for return to normal living; (vi) Peak flow velocity of >40 cm/s in
recipient artery [43]. We generally agree with the suggested inclusion criteria with the
exception of the significant renal disease. In our experience, we have not found an
increased risk for failure of free tissue transfers despite the fact that uremia may result in
a decrease in cell mediated immunity and impaired wound healing [44, 45]. Renal trans-
plant patients who were immunosuppressed had an odds ratio of 4.857 of having flap
failure (p = 0.041). The microsurgery technique involves using small recipient vessels
rather than a major vessels for reconstruction [46]. The most important factor associated
with success or failure of the graft may be the perfusion of the recipient vessel. Small
recipient vessels with good pulsatile flow are amenable to microsurgery whilst and an
absolute contraindication to free tissue transfer would be the absence of perfusion from
any distal small vessels.
The biggest challenge in reconstructive microsurgery for diabetic foot wounds is iden-
tifying an recipient vessel. Even with visual pulsation in the pedal arteries, atheroscle-
rosis, and calcification can make the anastomosis very difficult. Careful examination of
CT angiograms may assist in finding reliable recipient vessels. Calcification spared seg-
ments of the major artery can be used for the anastomosis in an end to side manner.
Alternatively, the anastomosis can be performed end to end in branches of major arter-
ies [12, 47, 48]. In our experience, using the branch from the major artery as a recipient
may be a better choice. It is relatively rare to see calcification in branches from the
posterior tibial and dorsalis pedis arteries, and technically one can easily anastomose to
a supple and soft artery without diminishing distal flow. An alternative anastomosis
may be the T-style anastomosis, where bypassing the artery segment with a branch to
the flap is inter-anastomosed between the proximal and distal recipient artery. If possi-
ble, we try to avoid using a major artery as an end to end fashion, as this method will
decrease the distal flow to the foot and will have a negative impact on the overall circu-
lation of the foot [12, 23].
The goals of flap reconstruction in diabetic foot wounds are: to provide a well vascular-
ized tissue to control infection; to provide adequate contour for footwear; maintain dura-
bility; resist shearing forces. Controversy still remains as to which flap offers the optimal
solution to reconstruct the foot (i.e. muscle flaps with skin grafts, fasciocutanous flaps,
and recently added perforator flaps), especially on the weight bearing surface. Regardless
of the specific flap, the principle of reconstruction is to cover these defects with well vas-
cularized tissue. A well performed flap provides an independent and well-nourished vas-
cular supply to eradicate infection, increase local oxygen tension, enhancing antibiotics
delivery and neovascularization to the adjacent ischemic tissue [49, 50]. In our clinical
experience we are shifting towards using perforator flaps (such as anterolateral thigh per-
forator flap, gluteal artery perforator flap and superficial circumflex iliac perforator flap)
466 29 Role of the Plastic Surgeon in Diabetic Foot Care

as these provide a thin flap to minimize shearing. These flaps utilize only the superficial
fat to imitate the fibrous septa of the sole to adhere tightly, enhance neovascularization of
the subdermal plexus with adjacent tissue and provide adequate blood supply to fight
infection
A report by Hong et al. reported that the microsurgical approach to reconstruct diabetic
foot wounds has high rates of flap survival rate and limb salvage (91.7 and 84.9% respec-
tively), which is similar with other reports [43, 51]. Failures were noted in patients with
peripheral artery disease requiring multiple angioplasties and renal transplantation
patients taking immunosuppressive agents [51]. Free flap reconstruction and limb salvage
may have not only improve quality of life, but may have a positive impact on patient
­survival. The death rate after five years for a major amputation can be as high as 78% [52–
54]. In our previous reported series, according to the Kaplan–Meier survival estimate curve,
the five-year survival rate for reconstructed patients compared to patients undergoing
major amputation was 86.8% and 41.4% respectively [51]. Although the average age (63 vs
54.6 years respectively) and ASA classification (2.7 vs 2.3 respectively) of the major ampu-
tated patients were relatively higher than the reconstructed patients in that series, it was
not statistically significant. If patients who underwent reconstruction using local flaps
were included in the overall data, potentially a greater difference favouring reconstruction
might be apparent.
The recent introduction of the supermicrosurgery concept provides an opportunity for
more options for the recipient vessels. Based on the concept that angiosomes around the
ischemic defects are healthier, surgeons can find a very small artery or a perforator to
use as a recipient vessel [23, 47]. The overall success rate for the supermicrosurgery
approach in diabetic foot wounds is 90.5%. Whilst this is slightly lower than nondiabetic
foot reconstruction, it compares favourably to diabetic foot reconstruction using the
classical approach [23]. A benefit of supermicrosurgery using the perforator flap is that
it provides well-vascularized tissue without being dependent on major vessels. This con-
cept may expand the indications for free tissue transfer in more severe cases of the
ischemic diabetic foot.
Figure 29.4 illustrates an approach with using the supermicrosurgery approach to recon-
struct a DFU.

29.9 ­Amputation

Lower extremity complications remain amongst the most common reasons for hospi-
talization in people with diabetes. There are cases where major amputations are inevi-
table. However, there is a role for the reconstructive surgeon even in patients
undergoing amputation. Soft tissue reconstruction by an experience plastic surgical
team can help preserve as much of the residual limb as possible. In some cases, pres-
ervation of the foot may be possible avoiding a major amputation. Similarly, recon-
struction may salvage a below knee amputation rather than proceeding to an above
knee amputation.
 29.10 ­Conclusio 467

(a) (b)

(c)

Figure 29.4 A 69-year-old patient showed necrosis and ischemic change on the medial aspect of
the metatarsal phalangeal join of the right foot (a). After endovascular approach and enhanced
circulation, the patient underwent complete debridement including part of the bone. A small
perforator was marked using a hand held Doppler and Duplex scan, A propeller flap was designed
based on this perforator (b). The flap was elevated, rotated to cover the defect and the donor site
needed a small skin graft. The flap healed uneventfully and the findings at one-year showed good
contour and well-maintained flap (c).

29.10 ­Conclusion

Plastic surgeons are an important component in any multidisciplinary approach for the
treatment of diabetic foot wounds. When technically feasible, the trend of management
has shifted from major amputation to limb salvage [13]. Using a team approach to address
the issues of perfusion, infection, wound treatment, off-loading, bone surgery, and soft
tissue coverage, the rate of major amputation is declining. Successful limb salvage is pos-
sible utilizing the principles of the reconstructive ladder and reconstructive elevator. See
Figure 29.5.
468 29 Role of the Plastic Surgeon in Diabetic Foot Care

(a) (c)

(b) (d)

Figure 29.5 A 71-year-old male patient with ischemic diabetic foot is noted with wound on the
dorsum of the left foot (a). Upon angiogram, the dorsalis pedis is not shown reflecting the wound
with the correlating angiosome (b). After angioplasty better flow was noted with an increased
velocity of the perforator from 13 to 21 cm/s (c). After debridement of the wound, a perforator of
the first metatarsal artery was used along with the accompanying vein to connect the superficial
circumflex iliac artery (SCIP) flap. The follow-up at two years six months shows good contour with
a well-preserved functioning foot (d).
   ­Reference 469

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lower extremity by means of microvascular free-muscle flap--a preliminary report. J. Vasc.
Surg. 12 (5): 581–585.
50 Chang, N. and Mathes, S.J. (1982). Comparison of the effect of bacterial inoculation in
musculocutaneous and random-pattern flaps. Plast. Reconstr. Surg. 70 (1): 1–10.
51 Oh, T.S., Lee, H.S., and Hong, J.P. (2013). Diabetic foot reconstruction using free flaps
increases 5-year-survival rate. J. Plast. Reconstr. Aesthet. Surg. 66 (2): 243–250.
52 Ecker, M.L. and Jacobs, B.S. (1970). Lower extremity amputation in diabetic patients.
Diabetes 19 (3): 189–195.
53 Goldner, M.G. (1960). The fate of the second leg in the diabetic amputee. Diabetes 9:
100–103.
54 Kucan, J.O. and Robson, M.C. (1986). Diabetic foot infections: fate of the contralateral foot.
Plast. Reconstr. Surg. 77 (3): 439–441.
 473

30a

Algorithms for Diabetic Foot Care

Management of the Hot Swollen Foot
Michael E. Edmonds, Chris Manu, and Nina Petrova
Diabetic Foot Clinic, King’s College Hospital NHS Foundation Trust, London, UK

The differential diagnosis of a hot swollen foot falls into two parts, the infected hot swollen
foot and the non-infected hot swollen foot [1] (Table 30a.1).
The infected foot can be divided into the cellulitic foot, with no obvious skin breakdown
or tissue loss and the cellulitic foot with tissue loss. Furthermore, the cellulitic foot with no
tissue loss can be divided into the neuropathic/neuroischaemic foot with cellulitis alone, or
with cellulitis and septic arthritis. The cellulitic foot with tissue loss can be further subdi-
vided into the neuropathic/neuroischaemic foot with ulceration and the Charcot foot with
ulceration.
The non-infected swollen foot can be divided into the Charcot foot, the foot with acute
gout [4], the lower limb with deep vein thrombosis (DVT) [5], and the critically ischaemic
foot [6].
To diagnose and treat a hot swollen foot, it is important to perform a thorough history,
examination and investigations. One cannot depend on one approach such as history alone.
It must be noted, that due to the presence of neuropathy and abnormal immunological
responses in diabetes, physical examination may be unremarkable for signs of infection
such as redness, increased warmth, or swelling. Also, indicators for infection or inflam-
mation such as leukocytosis may be absent [7]. Because of peripheral neuropathy, it may be
necessary to perform extra imaging than otherwise would be needed in a patient with an
intact peripheral nervous system.
Table 30a.1 describes the main features to observe in the history, examination, and inves-
tigations to determine the various causes of the hot swollen foot. Attention to these features
should lead to the correct diagnosis and then appropriate treatment.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
Table 30a.1

Infected Foot with cellulitis

No tissue loss
Neuropathic/ neuroischaemic foot
History
Examination ●● Redness of the skin in a hot
swollen foot which may quickly
extend to the leg
Severe or rapidly progressive
●●
cellulitis may lead to necrotising
fasciitis with blistering erosions
and pustules or haemorrhagic
bullae.
●● Crepitus of the skin from gas in
soft tissues
Tissue loss
Septic arthritis Neuropathic/ neuroischaemic Charcot foot with ulceration
ulceration
Rapid onset of unilateral erythema and swelling of foot and leg;
Shivering, chills, nausea and vomiting if septic
Swelling and erythema of foot and leg not affected by elevation;
Tenderness according to degree of neuropathy
Local lymphangitis and lymphadenopathy
●● The ankle joint may develop Skin breakdown
infection with minor but non Ulceration
apparent skin breakdown as Cellulitis
portal of entry of infection
Necrosis
●● Focal swelling of hind foot in
the background of general ●● Neuropathic ulceration: ●● Ulceration over bony
swelling of the foot predominantly on the sole of the prominence in patients
●● May have discomfort/pain foot, associated with neglected with medial convexity
alone or with ankle callus deformity or rocker
dorsiflexion and plantar ●● Neuroischaemic ulceration: bottom foot deformity
flexion depending on the predominantly on the margins of
degree of neuropathy. the foot, including the tips of the
toes and the areas around the back
of the heel
●● Crepitus of the skin from gas in
soft tissues
●● Probe to bone test to assess for
osteomyelitis [2].

Investigation ●● Culture of tissue from pustules,
erosions or ulcer to determine
causative organism
●● Blood culture
●● Foot and ankle X-ray to detect
gas in soft tissues
Treatment Wide spectrum antibiotics until causative organism known and then antibiotics to target organism.
●● The patient should rest and
elevate the affected limb.
●● The edge of the involved area of
erythema should be marked to
monitor progression or
regression of the infection.
●● If necrotising fasciitis or gas in
tissues diagnosed, urgent
surgical debridement should be
carried out.
Full blood count may show leukocytosis, but not necessarily so
Serum C-reactive protein - elevated
●● Foot /ankle X-ray to detect ●● Culture of tissue from ulcer/necrosis to determine causative
signs of septic arthritis: loss of organism
joint space, erosions, ●● Foot X-ray to detect osteomyelitis /foreign body in penetrating
destruction of subchondral injury
bone ●● When X-ray normal, MRI to detect osteomyelitis [2].
●● If X-ray normal, MRI to detect ●● Bone biopsy to detect osteomyelitis on histology and culture [2]
early signs of septic arthritis
namely synovial enhancement
and joint effusion
●● Ultrasound to detect joint
effusion and facilitate
aspiration of joint fluid, which
may contain pus cells and on
culture reveal the causative
organisms.
●● Assess for lower limb
ischaemia
●● If in the hind foot, the infected ●● Treatment with oral or intravenous antibiotic therapy over the
joint should undergo drainage duration of six weeks or more depending on the presence of
and wash out in theatre. osteomyelitis [3]
●● The patient should rest and ●● In cases where the infection is extensive or fails to respond to
elevate the affected limb. antibiotic therapy, surgery can be performed to resect infected
●● If the limb is significantly bone with a short course of antibiotic therapy postoperatively [3]
ischaemic, then it should be
revascularised.
(Continued)
Table 30a.1 (Continued)
Charcot foot
History ●● Sudden onset of swelling and
erythema of foot.
●● Patient cannot put foot in shoe.
●● There may be a history of minor
trauma such as tripping,
twisting the ankle or walking
over rough surfaces such as
cobbles.
●● About 30% of patients complain
of pain or discomfort.
●● Rarely, pain may be very severe
●● Charcot osteoarthropathy may
follow injudicious mobilisation
after surgery, a period of bed
rest or casting.
Non-Infected foot
Gout
●● Rapid onset of severe pain in
the foot usually in the
inflamed first metatarsal –
phalangeal joint at the base of ●● Heavy ache in the leg
the first toe.
●● This may follow joint injury.
Patient may be taking drugs
that lead to raised uric acid
such as diuretics, cyclosporine
or chemotherapy.
●● The attack will normally
subside within 3 to 10 days.
●● Past history of gout involving
foot or other joints.
Deep Vein Thrombosis (DVT) Critically ischaemic foot
●● Leg pain or tenderness in one or ●● Gradual onset of swelling
both legs, which may occur only of the foot usually
while standing or walking. associated with pain
across the dorsum of the
●● There may be a recent history of
foot and toes.
immobility, (including extended ●● Sitting or hanging the
bed rest due to injury or illness or foot out of bed can often
prolonged travel in a car or relieve the pain.
aeroplane. ●● Initially, there may be no
●● Other factors tissue loss.
Pregnancy
Contraceptive therapy
Smoking
Cancer
Surgery that damages the veins in the
leg
Family history or genetic
predisposition to forming blood clots
Obesity
 Charcot foot Gout Deep Vein Thrombosis (DVT) Critically ischaemic foot

Examination ●● Unilateral erythema and ●● Affected joints are hot, swollen ●● Swelling of the lower leg especially ●● The foot is pink and
swelling of foot relieved by and red and not affected by below the knee but may also swollen with pallor on
overnight elevation. elevation. involve the thigh. elevating the foot and
●● Classically the foot is at least 2°C ●● Usually there is marked ●● Warmth in the skin of the leg erythema on dependency
hotter than the contralateral foot tenderness which may be not ●● Red or discoloured skin in the leg. (Buerger’s sign).
as measured with an infrared skin so apparent as in non‐diabetes ●● The calf may be tender to ●● The colour of the
thermometer but acute Charcot because of neuropathy. palpation. dependent ischaemic foot
foot may be present with a smaller Skin over the joint is shiny and can be a deceptively
skin temperature difference
●●
●● Dorsiflexion of the foot may be healthy pink or red,
red. painful.
●● In the late presentation, ●● Occasionally there is fever. caused by dilatation of
deformity may have developed capillaries in an attempt
●● Gouty tophi may be present in to improve perfusion [4].
in the forefoot, mid‐foot and foot or elsewhere
hind foot and ankle. ●● The ischaemic foot is
●● The mid‐foot is the commonest usually cold. However, in
site of Charcot osteoarthropathy patients with diabetes,
and is recognised clinically by and autonomic
the medial convexity and rocker neuropathy the
bottom deformities. temperature of an
●● The medial convexity is associated ischaemic foot can be
with the classical Lisfranc’s tarso‐ normal or even elevated.
metatarsal fracture‐dislocation.
●● The rocker bottom deformity
develops when there is
disintegration and displacement
of the cuneiforms or the proximal
tarsal bones, resulting in collapse
of the mid‐foot. Rocker bottom
deformity is frequently associated
with plantar ulceration.
●● When the hind foot is involved,
the early presentation is of a
swollen ankle.
●● Later, there is severe structural
deformity and instability of the
ankle joint. This can lead to a flail
ankle on which it is impossible to
walk. Ulceration can often develop
over the malleoli.
(Continued)
Table 30a.1 (Continued)
Charcot foot
Investigation ●● Full blood count may rarely
show leukocytosis
●● C‐reactive protein may be
mildly elevated
●● X‐rays foot (straight and
oblique) and ankle (straight and
lateral) also lateral of the foot
and ankle (X‐rays standing if
possible). However, when
patients present early in the
acute active phase, X‐ray may be
normal.
●● Further investigations are then
necessary. An MRI examination
will portray soft tissue and bony
damage, including bone oedema
●● A technetium methylene
diphosphonate (MDP) bone
scan can detect early evidence
of bone damage by
demonstrating focal areas of
increased uptake of
radionuclide. Recently single‐
photon emission computer
tomography (SPECT‐CT) can be
carried out in addition to the
conventional bone scan. If the
bone scan is negative, then this
rules out a Charcot foot.
Non-Infected foot
Gout
●● Full blood count may show
leucocytosis
●● C‐reactive protein is elevated
●● Serum uric acid is usually
raised but not always
●● X‐ray of the foot may show
erosions in affected joints.
●● Aspiration of joint and
microscopy of joint fluid to
detect urate crystals.
●● As joint infections can also
cause similar symptoms to
gout, joint fluid can be
assessed for infection.
Deep Vein Thrombosis (DVT)
●● Measuring D‐dimer in blood ‐
usually used to rule out DVT.
●● D‐dimer may be raised in
infection, malignancy and post
operatively.
●● Duplex scan of the veins of the leg
to demonstrate obstruction. Blood
flow in normal veins is
spontaneous and phasic with
respiration and can be increased
by manual compression distal to
the ultrasound probe. When the
phasic pattern is absent, flow is
defined as continuous, indicating
the presence of venous outflow
obstruction.
Critically ischaemic foot
●● Initially, the ABPI should
be measured,
supplemented by
assessment of the arterial
Doppler waveforms.
●● Further tests such as
measurement of
transcutaneous oxygen
tension and toe pressure
may be helpful in
assessing degree of the
ischaemia.
The degree of ischaemia
●●
is thus assessed both
clinically and with non‐
invasive haemodynamic
investigations.
●● Visualisation of the lower
limb arteries can be
achieved with Duplex
ultrasound, computed
tomography angiography
(CTA) and magnetic
resonance angiography
(MRA).

Charcot foot
Treatment ●● The foot is initially immobilised
in a non‐weight bearing total
contact cast. The cast is checked
after 1 week, and replaced if it
has become loose due to
reduction of swelling.
●● It is regularly checked and
replaced as necessary. The
patient should use crutches and
be encouraged to avoid
weight‐bearing on the affected
side.
●● In many cases it is difficult to be
completely non‐weight bearing
because the patient has multiple
co‐morbidities including loss of
proprioception, postural
hypotension, high body mass
index and, in some cases,
neuropathy of the upper limbs,
all of which can make it
difficult to use crutches.
●● An alternative treatment is a
prefabricated walking cast, such
as the Aircast. A moulded insole
should replace the standard
insole provided with the cast by
the manufacturer.
●● However, the hind foot Charcot
is probably best treated in a total
contact cast.
Non-Infected foot
Gout
●● Attacks of gout can be treated
with non‐steroidal anti‐
inflammatory drugs
(NSAIDS),[5]
●● Prednisone can be given to
patients who can’t take
NSAIDs. Prednisone is usually
given by mouth with the dose
tapered down over 10 to
14 days.
●● Colchicine can be given orally
to relieve an acute gout attack.
●● Colchicine is usually effective
if taken within 12 to 24 hours
of a gout attack.
Deep Vein Thrombosis (DVT)
●● For patients with proximal DVT of
the leg, anticoagulant therapy is
recommended for 3 months [6].
Choice of drug depends on patient
factors such as hepatic/renal
function, pregnancy, cancer,
obesity, and bleeding risk.
●● For patients with an acute isolated
distal DVT of the leg but without
severe symptoms or risk factors for
extension, serial imaging of the
deep veins for 2 weeks is
recommended.
●● Anticoagulation is generally not
needed if the thrombus does not
extend.
●● Extension of the thrombus is
generally an indication to start
anticoagulation.
Critically ischaemic foot
●● The critically ischaemic
foot should be referred
urgently to a vascular
opinion.
●● In some patients,
increased perfusion may
be achieved by
angioplasty.
●● However, unless there is a
very significant localised
stenosis in iliac or
femoral arteries,
angioplasty rarely
restores pulsatile blood
flow to the foot which is
necessary to keep the
limb viable in critical
ischaemia. This is best
achieved by arterial
bypass which may need
to be to the distal
circulation [7].
480 30a Algorithms for Diabetic Foot Care

­References

1 Humphreys, W. (1999). Lesson of the week the painful red foot – inflammation or ischaemia?
Br. Med. J. 318: 925–926.
2 Lipsky, B.A., Aragon-Sanchez, J., Diggle, M. et al. (2016 Jan). IWGDF guidance on the
diagnosis and management of foot infections in persons with diabetes. Diabetes Metab. Res.
Rev. 32 (Suppl 1): 45–74.
3 Senneville, E. and Robineau, O. (2017). Treatment options for diabetic foot osteomyelitis.
Expert Opin. Pharmacother. 18: 759–765.
4 Shekelle, P.G., Newberry, S.J., FitzGerald, J.D. et al. (2017). Management of Gout: a
systematic review in support of an American college of physicians clinical practice
guideline. Ann. Intern. Med. 166: 37–51.
5 Merli, G., Galanis, T., Eraso, L. et al. (2017). Deep vein thrombosis. BMJ Best Practice. http://
bestpractice.bmj.com/topics/en-gb/70 (Last accessed 6 Feb 2018).
6 Slim, H., Tiwari, A., Ahmed, A. et al. (2011). Distal versus ultradistal bypass grafts:
amputation-free survival and patency rates in patients with critical leg ischaemia. Eur. J.
Vasc. Endovasc. Surg. 42: 83–88.
7 Armstrong, D.G., Lavery, L.A., Sariaya, M., and Ashry, H.J. (1996). Leukocytosis is a poor
indicator of acute osteomyelitis of the foot in diabetes mellitus. Foot Ankle Surg. 35 (4):
280–283.
 481

30b

Approach to a New Diabetic Foot Ulceration

Prashanth R.J. Vas and Michael E. Edmonds
Diabetic Foot Clinic, King’s College Hospital NHS Foundation Trust, London, UK

30b.1 ­Introduction

Diabetic foot ulceration (DFU) is common with an estimated lifetime incidence between 19
and 34% and often very challenging to treat [1]. Less than half of new DFU heal within
12 weeks [2] and in the EURODIALE study, nearly a quarter had yet to heal at 1 year [3]. It
is understood that greater than 50% of all DFU are infected at some point and approxi-
mately 17–20% of those with infection undergo some level of amputation [1, 4]. In the
United Kingdom, 135 of such procedures are conducted per week, with figures demon-
strating a rising trend, while in the United States of America (USA), figures published by
the Centre for Disease Control and Prevention, estimated rate 3.2 per 1000 diabetic popula-
tion for lower extremity amputation in 2009, adjusted for age. The presence of peripheral
vascular disease adds an additional dimension of complexity and increases the risk of
infection, slow- healing, hospitalisation, and amputation [1, 4]. In addition, non-healing,
DFU can lead to significant disability and increased morbidity [5–8] and overall, DFU is
associated with an increased mortality risk ranging from 5–15% at one year [4, 9, 10] up to
70% at five years, a rate higher than many common cancers [1, 10, 11]. Furthermore, the
associated treatment costs are substantial. In England, for the year 2014–2015, the direct
attributable cost of managing DFU was estimated to be more than £1 billion [12].
Development of DFU can lead to significant limitation of health-related quality of life, a
proportion of which persists despite improvement or healing of the DFU, underscoring the
frailty of the individual both in physical but also psychological domains [13]. Thus, the
morbidity, recognised slow healing rates, high economic costs, and the high mortality asso-
ciated with DFU make a compelling case for early recognition and prompt treatment initia-
tion of any new-onset DFU.
The approach to a new DFU, thus, falls into two main processes: (i) Clinical Care pro-
cess – an expert multidisciplinary foot service (MDFS) providing best practice care to
facilitate DFU healing, irrespective of the etiology; (ii) Structural process – providing the
framework for foot risk characterisation, foot protection, clear referral pathways when a

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
482 30b Approach to a New Diabetic Foot Ulceration

new DFU is noted and a high-quality preventative/protective service. In this overview, we

will focus primarily on clinical care and algorithms to facilitate healing, but it is important
to place emphasis and stress the importance of the overarching structural process.

30b.2 ­Clinical Care for the Management of DFU

Patients with a new DFU should be prioritised for rapid assessment by a specialist MDFS.
Delay in referral has been shown to be associated with poor outcomes, including longer
healing rates and greater risk of amputation [14]. Although guidelines vary, people with an
active foot problem (not self-presenting) should be referred to the MDFS within one work-
ing day and triaged within one further working day with the aim that all MDFS new DFU
referrals to be seen (open access) within 24 working hours.

30b.2.1 Patient Assessment

At initial visit, a detailed medical and drug history should be sought. In addition, informa-
tion should be acquired on diabetes control, diabetes related complications (and treatments
received), neuropathic pain and symptoms of lower limb vascular insufficiency. Many indi-
viduals with DFU have difficult socioeconomic circumstances as well as psychological
challenges [15]. A clear picture early on will help tailor how clinical information is deliv-
ered and accepted. Box 30b.1 describes the baseline assessments required when assessing a
new DFU and Table 30b.1 summarises the initial laboratory, radiological, and microbio-
logical investigations undertaken.

30b.2.2 DFU Assessment

A clear assessment of the DFU should be made to include wound characteristics, presence
of features of infection and importantly, the current vascular status. Documentation of
wound size, area, depth alongside the quality of tissue present within the ulcer are impor-
tant (Box 30b.1).

30b.2.2.1 Identification of Infection

Recognition of infection is one of the most important but also one of the most challenging
aspects. Between 50 and 90% of DFU are infected by the time they present [4]. Typical fea-
tures of infection include pain, increase in exudate, skin and soft tissue oedema, and cel-
lulitis when there is spread of infection through the soft tissues. The latter is sometimes
difficult to identify in darker coloured skin. The neuro-immunomodulation of diabetic
neuropathy, however, while making the ulcer more susceptible to infection, may also mask
the typical symptoms and signs. Foul odour, friable/discoloured tissue, undermining of
wound edge, week on week increase in exudate and poor granulation could be considered
secondary surrogate indicators of infection [16]. Microbiological samples should be sent
away when clinical infection is suspected, preferably, tissue specimens [17]. In those with
suspected diabetic foot osteomyelitis (DFO), attempts should be made to obtain a bone
specimen. While, superficial swabs of DFU are discouraged [17], a good deep wound swab,
 30b.2 ­Clinical Care for the Management of DF 483

Table 30b.1 Investigations undertaken at the Kings College Hospital Diabetes Foot Clinic for a DFU.
Please note a valid test for neuropathy/loss of protective sensation is also undertaken but has not been
included. All patients without easily palpable pulses will have duplex waveforms assessed as standard.

Hematology Biochemistry Radiology Vascular Lab Microbiology

Full Blood Urea and X-Ray Foot and able Duplex Tissue specimen
Count Electrolytes with weight bearing waveforms or deep swab for
views. Ensure clear culture (when
views of calcaneal tissue specimen is
available for hind not possible)
foot DFU.
Erythrocyte Liver Function MRI Foot Full arterial Bone or Pus for
Sedimentation tests Duplex if culture where
Rate waveforms possible
suggestive of
arterial disease
C-Reactive protein WBC Radionuclide TcPO2 (in
scanning with selected cases)
SPECT (as an
alternative for MRI
or if MRI equivocal)
HbA1C (Glycated Ultrasound imaging
haemoglobin) and and diagnostic
Lipid profile aspiration (where
appropriate)
Vitamin B12,
Folate, Iron profile
(where
appropriate)

MRI = Magnetic Resonance Imaging, SPECT = Single Photon Emission Computed Tomography,
TcPO2 = Transcutaneous Oxygen Tension measurement

obtained after thorough cleansing and debridement may be of value in specific instances.
Sadly, there is limited current evidence available to determine the optimal sampling tech-
nique [18] and more research is urgently needed. Rapidly spreading cellulitis, blistering/
necrosis of skin are features of limb threatening infection and may be accompanied by
systemic features such a temperature > 38 °C, tachycardia (>90 beats/min), tachypnoea
(>20 breaths/min) and muscle aches and should prompt admission to hospital, even at the
first visit [19].

30b.2.2.2 Excluding Peripheral Vascular Disease

There is a distinct difference in the presentation, temporal healing trends and in the manage-
ment of the two major presentations of DFU: neuropathic DFU and neuroischaemic DFU.
Purely ischaemic DFU exist (often presenting as tissue necrosis secondary to critical or acute
limb ischaemia) but are proportionally a distant third subtype (or a variant of neuroischaemic
ulceration if high end assessments of neuropathy detection are employed). Characterisation of
peripheral arterial disease (PAD) is an important early step and should be ideally undertaken at
484 30b Approach to a New Diabetic Foot Ulceration

the first visit, or as soon as possible. Palpation of pedal pulses is recommended in a number of
guidelines but data on inter-observer variability and accuracy is conflicting. Therefore, this is at
best a screening test. The International Working Group on the Diabetic Foot (IWGDF) recom-
mends the use of bedside non-invasive tests as first line, but without advocating one particular
modality as optimal [20]. An ankle brachial index (ABI) of >0.9, presence of triphasic pedal
Doppler waveforms or a toe brachial index of ≥0.75 suggest the absence of PAD. Vascular calci-
fication may result in a falsely elevated ABPI thus a ‘normal’ ABPI does not rule out PAD on the
other hand in those with an ABPI of <0.9 in the presence of vascular calcification the true arte-
rial pressure may be considerably lower than suggested by the Doppler measurement.
Measurement of toe blood pressure (≥30 mmHg increases pre-test probability of healing by
25%) and transcutaneous cutaneous oxygen tension (TcPO2, ≥25 mmHg) may also provide
important information and prognosticate the potential for healing [21]. Critical Limb Ischaemia
(CLI), where the perfusion to the lower limb or pedal arteries is severely reduced and the viabil-
ity of the tissue compromised (presence of ulceration, gangrene, or pain at rest), is characterised
by an ankle pressure typically between 50 and 70 mmHg (or lower) or toe pressures <50 mmHg
or transcutaneous oxygen tension (TcPO2) <30 mmHg [22]. Those with neuroischaemic DFU
should receive a fast-tracked vascular consult and the extent (often multilevel) and severity of
PAD should be ascertained.

30b.2.2.3 Ulcer Classification

An accepted system of DFU classification will help communication between various members
of the MDFS and provide an overview of DFU progression. Many classification and scoring
systems for DFU exist, with varying degrees of validation [23]. While the University of Texas
classification and the Wagner classification systems have been widely utilised, the United
Kingdom National Diabetes Foot Audit has adopted the Site, Ischaemia, Neuropathy, Bacterial
Infection, Area and Depth (SINBAD), which by virtue of its simple scoring system and relative
quickness allows for evaluation of high volume data between multiple centres and benchmark
clinical outcomes. The recently introduced Wound, Infection, Ischaemia (WIFI) has been
shown to prognosticate risk of lower extremity amputation and DFU healing [24].

30b.2.3 Footwear
Biomechanics play an important role in achieving wound stabilisation and healing.
Therefore, documentation of foot shape, any associated deformities and their relevance to
the DFU is important. Review of current footwear and mobility aids is also equally ­essential.
Abnormalities of foot pressure can be present early in the course of diabetic neuropathy.

30b.2.4 Imaging
Imaging the foot is important. Indeed, we believe it should be an extension of clinical
examination. The aim of imaging is to exclude soft tissue gas or presence of foreign body,
provide supportive information to differentiate soft tissue infection from DFO, evaluate the
impact of structural abnormalities and in the serial evaluation/monitoring of post-surgical
changes. Plain radiography (X-ray) should usually be undertaken at the first visit or the
earliest available opportunity in all DFU’s; in addition, a repeat X-ray should be considered
 30b.3 ­Management of DF 485

if there is further clinical change. For the detection of DFO, the sensitivity (40–60%) and
specificity (60–90%) of plain radiography is low, particularly in early DFO as changes may
take up to two weeks or longer to manifest. Magnetic resonance imaging (MRI) is currently
considered as the main imaging modality for the detection of DFO with high sensitivity
(88–100%) [25], and specificity (40–90%). MRI can also delineate the extent of soft tissue
involvement and detect deep collections (Table 30b.1).

30b.2.5 Laboratory Blood Panel

Laboratory assessments help provide a metabolic overview of the individual, influence,
and support management. In the setting of an acute infection or when DFO is present, a
rise in white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) may occur [17], but not always so. Improvement in these parameters have
been shown to be predictive of DFU healing, DFO remission, and may even indicate DFO
recurrence [26]. The glycated haemoglobin (HbA1C) indicates recent glycaemic control
which may require optimisation. Renal and liver function give an indication of general fit-
ness and need to be monitored to ensure safe administration of antibiotics (Table 30b.1).

30b.3 ­Management of DFU

The approach to the management of a new DFU has six major components (Box 30b.2).

30b.3.1 Wound Control

Any callus surrounding the ulcer should be removed by sharp debridement together with
removing slough and non-viable tissue from the ulcer edge and base. This is also an oppor-
tune time to assess depth and determine if the ulcer tracks down to the bone [17]. The current
guidelines from the IWGDF and American Podiatric Medical Association/Society for Vascular
Medicine do not support the use of any one single dressing type [27, 28]. Application of a
sucrose octasulphate dressing has been recently shown to improve wound closure of neurois-
chaemic DFU at 20 weeks (adjusted odds ratio 2.6, 95% CI 1.43–4.73; p = 0.002) [29]. Post-
operative wounds, or those which have been extensively debrided in clinic, may benefit from
negative pressure wound therapy (NPWT) to enhance healing [28]. Adjunctive therapies
such as platelet concentrates, platelet-derived growth factors, extracellular matrix products,
amniotic membrane products, epidermal growth factors, bioengineered skin, low level laser
and hyperbaric oxygen therapy have, as yet, limited evidence of efficacy to justify adoption
into routine practice. In addition, larval debridement therapy may have a role in challenging
sloughy ulcerations where sharp debridement is not possible or very painful.

30b.3.2 Vascular Control

Neuroischaema is present in 45–60% of all DFU. Those with CLI, will require urgent revas-
cularisation – either endovascular or surgical to prevent deterioration of the DFU and to
achieve limb salvage [30, 31]. Those on dialysis have higher prevalence of neuroischaemia.
486 30b Approach to a New Diabetic Foot Ulceration

Box 30b.1 Initial Assessments Required at Initial Review of a DFU (See Below)

Examination
History

First DFU or previous history present Determine if foot is neuropathic, or

Previous leg/foot ulcer or lower limb,
amputation/surgery
Prior angioplasty, stent or leg bypass
surgery
Smoking?
Duration of Diabetes, current control
Ascertain if associated comorbidities –
cardiac, renal, liver
Social, drug and psychological history
Vision, Mobility aids used? Carer support?
Employment status
neuro-ischaemic (feel for foot pulses)
Look for features of critical limb ischaemia
(pain, necrosis)
Are there musculoskeletal deformities
inlcd Charcot foot changes
Cardiovascular examination
Dermatological examination
Appropriateness of current Footwear

DFU Characteristics DFU Clinical Workshop at First Visit

Classify DFU. Location:medial/lateral, Organise formal non-invasive vascular

plantar/dorsal, toe, interdigital, forefoot,
midfoot, hindfoot.
Document wound size and depth.
Clinical signs of infection and presence of
exudate: Amount of exudate, colour, odour,
viscosity or frank pus. Is there cellulitis?
Does it probe to bone?
Presence and quality of surrounding callus
Look for undermining/tracks/sinuses
Quality of surrounding skin
Leg Oedema
Presence and nature of PainIf more than
one DFU is present, assess individually
and check if there is a physical link or track.
assessment-local guidance may vary,
Doppler waveform is a good start. If
monophasic, organise full arterial duplex
and vascular review
Bloods on first visit (see Table 30b.1)
Basline imaging (see Table 30b.1)
Ensure a microbiological specimen for
culture is obtained if there are clinical
signs of infection.
Need to ensure a clear management plan is
initiated, discussed with patient and followed
through. Reinforce education, add clarity on
weight bearing, provide approprite offloading
footwear

Healing and amputation free survival is significantly reduced compared to those not on
dialysis [32]. Often, and including in our practice, those with milder PAD are observed
closely within the MDFS with supportive wound care. Revascularisation is undertaken if
the DFU shows deterioration or is slow to progress. Recent advances in interventional radi-
ology alongside ultra-distal/pedal bypass surgery within an integrated pathway have facili-
tated delivery of complex revascularisation [5]. Figure 30b.1 provides a schematic approach
to the management of a non-limb threatening DFU.

30b.3.3 Mechanical Control

In neuropathic DFU, the overall aim is to redistribute plantar pressure. The choices avail-
able include the total contact cast (TCC), or a prefabricated cast such as Aircast Diabetic
Pneumatic Walker™ (or equivalent, when a non-removable device is contraindicated),
 30b.3 ­Management of DF 487

Box 30b.2 Components of DFU Control. DFU = Diabetic Foot Ulceration

Wound
Control

Vascular
Education
control

DFU

Metabolic Mechanical
control Control

Infection
control

Scotchcast boot or temporary shoes with a cushioning insole or a wedge to provide forefoot
or heel offloading such as the DARCO™ boot. Among these, the TCC is the currently
accepted ‘gold standard’ [33]. Semi-compressed adhesive felt padding may be used to divert
pressure, especially from small neuropathic DFU’s. In those with neuroischaemic DFU,
TCC is a relative contraindication. Those with chronic or recurrent ulcerations resulting
from high pressure points related to bony deformities should be considered for surgical
offloading. Although the majority of data for surgical intervention comes from case series,
rather than controlled studies, they are nonetheless, quite encouraging.

30b.3.4 Microbiological Control

Infection in DFU can range from mild, local involvement to severe limb-threatening infec-
tion with severe necrosis and systemic features [17]. Debridement of surrounding callus,
removal of slough and necrotic tissue along with thorough cleansing will reduce the micro-
bial bioburden in mildly infected DFU and may be all that is needed [17]. The choice of
antibiotic depends on the patients’ geographical location, past infection status, previous
antibiotic exposure, comorbidities as well as the allergy status. Empirical oral antibiotic
therapy should definitely target gram-positive organisms (Staphylococcus aureus and strep-
tococci). However, those with chronic DFU’s where the bacterial milieu is typically polymi-
crobial or with those with suspected or known antibiotic resistant organisms may need to
488 30b Approach to a New Diabetic Foot Ulceration

New Foot Ulcer in someone with diabetes

Detailed Ulcer Classification

Presence of Diabetic Neuropathy?

Yes No

Presence of peripheral arterial disease? Presence of peripheral arterial disease?

No Yes Yes No

Neuropathic DFU Neuroischaemic DFU Ischaemic DFU Consider differential

diagnosis:
Rheumatology or
Assess for ulcer depth and presence of infection. Note Site of DFU. dermatology related
Exclude concomitant Charcot. In Neuroischaemic DFU, involve vascular surgery early Involve vascular (e.g vasculitis,
surgery urgently malignancy)

Ulcer, Ulcer with cellulitis Ulcer with underlying Ischaemia, but not critical and
Critical Limb ischaemia Involve specialist
no infection or soft tissue infection osteomyelitis not known to be non/slow- teams+
healing. Decision to monitor
or already known to be
non/slow-healing Support as
made.
Neuropathic DFU
Sharp debridement Sharp debridement and Sharp debridement and Until investigations
and wound care wound care wound care
DFU management as in Organise angioplasty or conclude
TCC or appropriate TCC* or Appropriate Bone culture targeted
Off-loading, Off-loading, Adequate Neuropathic DFU pathway surgical bypass to
antibiotics,
infection control, Early input from orthopaedic facilitate healing or
Supportive medical surgery, tissue loss control.
care Supportive medical care Podiatric or surgical removal
of sequestrum where
Healing as predicted
necessary, (4–6 weeks)
Involve vascular
TCC or appropriate Off- DFU management as in surgery early
loading, Neuropathic DFU pathway
Supportive medical care.
Yes No

Healing as predicted (4–6 weeks) Further assessment Healing as predicted

in 4–6 weeks, (4–6 weeks)

Healing as
Yes No
predicted?
No Yes

Ensure appropriate bespoke Revisit Ischaemia,

footwear/orthotics provided,
Ensure CVD risk optimised,
Supportive medical care,
Close supervision for recurrence
once healed (follow up in DFC or
community foot health clinic),
Patient education on ongoing
foot care.
Revisit offloading technique, Yes No
Revisit infection-consider
surgical debridement of infected
tissue + May need continuation of
antibiotics or change in antibiotics
to reflect current pathogens,
Ensure appropriate bespoke
Discuss home environment, footwear/orthotics provided,
Assess compliance Vascular surveillance as per local
Consider surgical offloading protocol for those with
angioplasty/bypass,
Ensure CVD risk optimised,
Supportive medical care

Close supervision for recurrence

once healed follow up in DFC or
community foot health clinic,

Patient education

Figure 30b.1 Schematic overview of the approach to a non-acutely limb threatening diabetic foot
ulceration (DFU). CVD = cardiovascular disease, DFC = Diabetic Foot Clinic, TCC = total contact cast

have bespoke antibiotic treatment from the outset. In our practice, Coamoxiclav, adminis-
tered thrice daily is now the primary empiric antibiotic of choice for mild infections in
penicillin tolerant individuals. The emergence of antibiotic resistant strains such as
Methicillin resistant Staphylococcus aureus (MRSA), Vancomycin resistant enterococci
(VRE) and multidrug resistant gram-negative organisms are proving a significant chal-
lenge in determining antimicrobial therapy in many outpatient MDFS clinics.
 30b.3 ­Management of DF 489

Moderate–severe infections should be considered as potentially limb-threatening (‘­diabetic

foot attack’) and may be the first presentation of a new DFU. These require admission to
hospital, intravenous antibiotics and possibly, early surgical debridement [19]. Empirical
broad spectrum intravenous antibiotics are recommended until microbiology results allow
for targeted therapy. Use of other agents is influenced by prior microbiology results. DFO
may require surgical excision of sequestrum followed by targeted antibiotic therapy guided
by bone culture. There is randomised controlled evidence for managing DFO with primary
antibiotic therapy. However, studies have been limited to low grade, forefoot predominant
DFO without significant soft tissue infiltration/extensive ulceration [34]. There is very little
consensus on the recommended duration of antibiotic therapy. Guidelines advocate between
2 weeks for mild infection to more than 12 weeks in those with advanced hindfoot osteomy-
elitis [17]. In addition, there is very little agreement on the most favourable antibiotic delivery
mode (oral versus intravenous) [17].

30b.3.5 Metabolic Control and Management of Comorbidities

As neutrophil function and wound healing is impaired by hyperglycaemia, tight glycaemic
control is recommended. Insulin initiation or consideration of newer anti-hyperglycaemic
agents may be necessary. Close liaison with the patients’ diabetes care team is important.
Cardiovascular risk optimisation and antiplatelet therapy should be considered as per local
guidelines. Smokers should be advised to stop and referred to smoking cessation services.
Furthermore, patients are likely to be less mobile whilst recuperating; focus on diet and
lifestyle control may also be important. Leg oedema may benefit from compression bandag-
ing and diuretic therapy – this may have additional benefits on wound moisture control.
Other tenets of care to consider would be ensuring adequate nutritional support, optimis-
ing anti-cardiac failure therapies, monitoring renal failure, anaemia correction and where
available, psychological, and social support.

30b.3.6 Education
Patient education in those who have already presented with a neuropathic DFU has two
main streams – to allow healing and to maintain remission. Most individuals with DFU
have loss of protective pain sensation and need advice on how to protect their feet from
mechanical, thermal, and chemical trauma [35]. In addition, they will require instruction
on the principles of ulcer care such as importance of rest, footwear, regular dressings, fre-
quent observation for signs of infection, and to ensure compliance with offloading devices.
In practice, it is useful to reinforce these principles at every clinic visit. It is also important
to ensure the advice is simple, memorable and in keeping with the individuals’ emotional,
educational, and cultural sensibilities. Effective education can be challenging and unfortu-
nately, there is little data to support the above statements. A recent Cochrane review con-
cluded that there was insufficient robust evidence for limited patient education in achieving
clinically relevant reductions in ulcer and amputation incidence [36]. Furthermore, the
increasing recognition of coexistent cognitive impairment in diabetic foot individuals [37]
only adds to the complexity.
490 30b Approach to a New Diabetic Foot Ulceration

30b.4 ­Structural Care Process in DFU Management

An integrated, structured framework of delivering risk assessment, foot protection, and

when DFU occurs prompt assessment bound by a predetermined referral pathway is the
key, fundamental process to improve outcomes in DFU in a contemporary context
(Box 30b.3). All individuals with diabetes should be expected to undergo a comprehensive
annual foot evaluation to identify risk factors and foot-risk stratification. If identified at
increased risk, individuals should be prioritised to receive foot protection and education
aimed at understanding the implications of such risk [38]. This is expected to be delivered
through community podiatry led ‘foot protection’ services with close liaison with primary
care teams (western European model). Through this process, those who develop a new
DFU can direct themselves to their foot protection service or primary care team immedi-
ately and an urgent onwards referral to the diabetic foot MDFS is then facilitated. The
International Working Group on Diabetic Foot (IWGDF) and National Institute of Clinical
Excellence and Health (NICE) recommend that all newly recognised DFU’s should be
referred to a MDFT within 24 hours [33, 39]. However, there is a remarkable degree of
uncertainty over how such a care structure is supported, with great variance in the uptake

Box 30b.3 Components of an Integrated Care Process for Diabetic Foot Care

Primary
Care

Foot-risk
MDFT
screening

Integrated
Care Process
for DFU
Continuous Community
training of FOOT
Staff protection

Clear
Social
referral
Support
pathway

DFU = Diabetic Foot Ulceration, MDFS = Multidisciplinary Diabetic Foot Service

  ­Reference 491

of recommendations [40, 41]. In addition to involvement of community podiatry and pri-

mary care teams, some individuals with DFU may present directly to the emergency
department (ED) [42] and therefore it is important to ensure local ED teams are acquainted
with the process DFU care management, especially when patients are not admitted. A well-
designed referral pathway and continuous training of all staff will allow smooth working
within the sectors and not allow at-risk individuals or those with new DFU to ‘fall through’.
A foot protection service should deliver high quality surveillance for those at increased risk
and those who have healed their DFU. It should be able to provide lifelong observation and
bespoke footwear. All the above should be underpinned by regular audit and reassessment
of the pathway to ensure the right care for the individual is providing in the ever-changing
environment of healthcare delivery.

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 495

30c

Algorithms for Diabetic Foot Care

Vascular Evaluation
G. Dovell1,2 and R.J. Hinchliffe1,2
1
Bristol, Bath and Weston Vascular Network, Bristol, UK
2
Bristol Centre for Surgical Research, University of Bristol, UK

30c.1 ­Introduction

Peripheral artery disease (PAD) is common in patients with diabetes and it has been
­estimated that 50% of patients with diabetic foot ulceration will have underlying PAD [1–
3]. Vascular evaluation of the diabetic foot is therefore essential and will guide subsequent
management, including the need for secondary cardiovascular therapy and revascularisa-
tion. PAD represents a significant facet of managing a diabetic foot ulcer (DFU) but there
are multiple factors at play including infection, biomechanics, oedema, and the patient’s
co-morbid status [4].
The pattern of PAD in diabetes is predominantly below the knee [5] and PAD has been
defined in diabetes by the international working group on the diabetic foot (IWGDF) as
‘any atherosclerotic occlusive disease below the level of the inguinal ligament, resulting in
a reduction in blood flow to the lower extremity’ [6]. Aorto-iliac PAD its pattern and man-
agement is largely similar between those with and without diabetes.
Is it essential to identify and treat underlying PAD in patients with diabetic foot ulcera-
tion because it is associated with adverse outcomes; including failure to heal and major
limb amputation [7, 8]. The diagnosis of PAD in patients with diabetes can be challenging.
People with diabetes typically lack the classic symptoms of PAD such as claudication and
rest pain, even in the presence of severe tissue loss [1, 9, 10]. What’s more, the presence of
a palpable pulse does not reliably exclude PAD and the presence of arterial calcification,
tissue oedema, neuropathy, and foot infection can confound the reliability of non-invasive
bedside tests [6].
Education plays a vital role in preventing the formation of a DFU and the absence of foot
pulses on examination identifies a group of patients at higher risk of ulceration to whom
education should be focussed and in whom yearly examination, including foot pulses, is
recommended. The presence of pulses does not exclude significant PAD [7, 11] and those
with ulceration should be evaluated in a multidisciplinary centre capable of both investi-
gating and managing these complex patients [6].

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
496 30c Algorithms for Diabetic Foot Care

30c.2 ­Methods of Vascular Evaluation – Detecting

Peripheral Artery Disease

30c.2.1 History and Examination

History and clinical examination may be able to suggest a diagnosis of PAD but do not reli-
ably exclude it. Elements of a history that would suggest PAD include, intermittent claudi-
cation, rest pain, previous ulceration, infection, or amputation. Clinical examination
findings that support a diagnosis of PAD include absent peripheral pulses, a cool lower
extremity, femoral bruits, and slow venous filling time [12]. Examination should also
include elevation of the foot with the patient supine to above the level of the heart and
subsequent lowering whilst the patient is in a sitting position; pallor on elevation and red-
ness on dependence suggests severe ischaemia. The absence of these signs however doesn’t
rule out significant PAD [10].
In patients without tissue loss, symptoms, and signs of PAD including claudication,
absent pulses, and low ankle brachial index (ABI) are predictors of future diabetic foot
ulceration [13]. It is recommended that these patients be reviewed on a regular basis by a
member of the specialist foot care team to assess and help prevent ulceration [6].
Palpation of foot pulses is affected by room temperature, oedema, and the skill of the
examiner. Reproducibility has been reported as moderate [12] and in the hands of a skilled
examiner palpable pulses do not rule out significant ischaemia or perfusion deficit [14] as
such, in patients with foot ulceration, clinical evaluation should always be supported by
objective testing.

30c.2.2 Non-invasive Bedside Testing

Non-invasive bedside testing can be used to diagnose or exclude PAD and help identify
which patients with a DFU are unlikely to heal and thus need further imaging and consid-
eration for revascularisation. Healthcare professionals should be aware of the limitations
of each method and should decide which to use given their local expertise and available
facilities. All should be performed by trained healthcare professionals in a standardised
manner and there is insufficient evidence to support the use of one test over another [15].

30c.2.2.1 Ankle Brachial Index (ABI)

ABI is conducted by measuring the systolic blood pressure of the brachial arteries and from
both dorsalis pedis and posterior tibial arteries using a handheld doppler and a suitable
pneumatic blood pressure cuff. The patient must be supine and the higher of the brachial
readings is used for the calculation on both sides. The ankle pressure of both dorsalis pedis
and posterior tibial is measured and the higher reading used to calculate the ABI in each
foot [15]. A normal ABI reading is between 0.9–1.3. An abnormal ABI reading is an inde-
pendent predictor of cardiovascular mortality and thus risk factor modification in these
patients must be applied accordingly.
An ABI of <0.9 is useful to identify PAD in people with diabetes who do not have neu-
ropathy. Peripheral diabetic neuropathy is associated with medial wall arterial calcification
and increases the likelihood of a falsely elevated ABI. This is defined as an ABI of >1.3
 30c.2 ­Methods of Vascular Evaluation – Detecting Peripheral Artery Diseas 497

which is also known to be associated with poorer outcomes and cardiovascular events.
High ABI often masks occlusive PAD [16–18] and less severe calcification may result in a
normal range ABI despite clinically significant PAD [19, 20]. Trust the ABI therefore, when
it is low.
In patients with ulceration, an ABI of <0.5 and or an ankle pressure of <50 mmHg iden-
tifies a group at higher risk of amputation [21] and indicates the need for urgent imaging
and subsequent consideration for revascularisation [6]. Vascular imaging is also recom-
mended with large or infected ulceration despite a higher or normal ABI [22].

30c.2.2.2 Ankle Doppler Signal

Using a handheld continuous wave Doppler audible signals can be demonstrated. Each
waveform has a characteristic sound created by the Doppler effect. A triphasic waveform is
characterised by systolic forward flow, early diastolic flow reversal and secondary forward
flow in late diastole. This is considered to represent normal flow and arterial elasticity. A
biphasic waveform has forward systolic flow and diastolic flow reversal, and monophasic
flow is most commonly defined as pandiastolic flow and considered grossly abnormal [23].
The demonstration of triphasic signals at the ankle provides strong evidence for the
absence of PAD [24] and an absent or monophasic signal is an indicator of severe PAD [4].
This technique is however limited by the skill of the operator to audibly recognise the
­signals correctly. Some newer handheld Doppler machines will print out a waveform
reading.

30c.2.2.3 Toe Pressures/Toe Brachial Index

This is conducted in much the same way as an ABI however the pressure in the digital ves-
sels (usually the hallux or second toe) can be measured using either laser Doppler (LD) or
plethysmographic methods; strain gauge or photoplethysmography are most commonly
used. The LD method has been shown to be more sensitive than photoplethysmography, it
is less affected by movement artefact and the toe does not require exsanguination, however
it is more expensive and requires substantially more equipment [25].
A normal toe brachial index (TBI) is >0.8 and a reading of ≥0.75 makes PAD unlikely. TBI is
more reliable than ABI at assessing the forefoot circulation as the readings are less likely to be
falsely elevated due to medial calcification. Toe pressures of <55 mmHg or TBI of <0.7 strongly
suggests PAD however both are affected by the foot surroundings and temperature [15]. In
patients with a DFU, a toe pressure of >30 mmHg increases the pre-test probability of healing
the DFU by at least 25% [26], conversely toe pressures of <30 mmHg, or a TBI of <0.35, would
warrant urgent vascular imaging and consideration of revascularisation.

30c.2.2.4 Transcutaneous Oxygen Tension Measurement (TcP02)

TcP02 is a non-invasive test that measures the partial pressure of oxygen perfusing through
the capillary beds. It is useful to compare peripheral and central readings. A normal TcP02
reading is roughly 60 mmHg and in a patient without diabetes a TcP02 of <30 mmHg con-
firms critical limb ischaemia. TcP02 is useful to predict ulcer healing [21] and measures
perfusion indirectly using heated electrodes. A TcP02 of >25 mmHg increases the pre-test
probability of healing a DFU by at least 25% [26]. However, the technique is not standard-
ised, and results can vary. TcP02 is also time consuming and less reliable in the presence of
498 30c Algorithms for Diabetic Foot Care

oedema and infection as well as being influenced by temperature, the presence of neuropa-
thy and ulcer location (it cannot be used to assess plantar ulceration due to the thickness of
the skin) [27]. Those patients with a DFU and a TcP02 of <25 mmHg should be considered
for urgent vascular imaging and revascularisation [6, 21].

30c.2.2.5 Skin Perfusion Pressure

Skin perfusion pressure (SPP) employs the use of a LD and pneumatic cuffs, identifying
perfusion pressure as the cuff is released. A SPP of >40 mmHg increases the pre-test prob-
ability of healing a DFU by at least 25% [26].

30c.2.2.6 Pulse Oximetry

Pulse oximetry has been suggested as a screening tool for PAD. A drop of 2% in saturation
from finger to toe measurement, or a drop of 2% on elevation of the foot was considered
diagnostic, however there is no consensus within the literature [28] and elevated
­glycosylated haemoglobin levels have been suggested to account for falsely elevated oxygen
saturations and low sensitivity [29, 30].

30c.3 ­Vascular Imaging

Vascular imaging is intended to demonstrate the distribution of PAD to aid both the deci-
sion to and inform the type of revascularisation. It should be considered in those patients
with tissue loss whom bedside testing has identified a severe perfusion deficit (as detailed
above). Those patients with acceptable or borderline bedside test results can be managed
with best medical/wound/foot care for up to six weeks; at which time if the ulceration is
not showing signs of healing, vascular imaging should be sought with an intention to revas-
cularise. There is no gold standard imaging technique and the modality chosen relies upon
the resources of the healthcare system and the professionals requesting and reporting
them. If an ulcer is failing to heal despite best management revascularisation of even minor
PAD with questionable haemodynamic significance should be considered [6].

30c.3.1 Colour Doppler Ultrasound

Colour Doppler ultrasound (CDUS) is colloquially known amongst physicians as a ‘Duplex
ultrasound scan’ due to the two imaging modalities it employs. Firstly B-mode ultrasound
imaging, which uses sound waves from piezoelectric crystals and provides a real time 2D
anatomical image; and secondly, by using pulsed Doppler flow detection from which veloc-
ity assessments can be made. This is usually displayed as a spectral waveform or colour
flow map with velocity (not flow). It is a non-invasive method of assessing the arterial sup-
ply from the aorta to the tibial vessels and PAD is identified and its severity quantified
based upon velocity changes derived from spectral waveforms [31].
CDUS requires an experienced professional to achieve accurate results and a full arterial
assessment can be time consuming [32]. The sensitivity of CDUS for detecting haemody-
namically significant PAD, which is classified as a stenosis of 50% or more, ranges from 89%
in the iliac segment, to 68% in the popliteal segment to, 82–90% in the runoff [33]. It can be
 30c.3 ­Vascular Imagin 499

useful to identify a patent target vessel for revascularisation often not appearing on com-
puter tomography or intra-arterial digital subtraction angiography (DSA); however, runoff
assessment is often difficult and operator dependent [34].
The limitations of CDUS include; obesity, bowel gas, leg oedema, pain, skin ulceration,
and degree of calcification. CDUS is non-invasive and relatively inexpensive but requires
expertise and specialist equipment therefore is not recommended for routine detection of
PAD. It is often the first line investigation when initial bedside tests are abnormal and is
used for preliminary clinical decision making regarding intervention and revascularisa-
tion, as it’s consistency with DSA has been reported at 94.6% [35]. However, interpretation
of the images in diabetic patients, who have a predilection to heavily calcified run off below
the knee, can be difficult and unreliable.

30c.3.2 Multidetector-Row Computed Tomography Angiography (MD-CTA)

MD-CTA uses intravenously injected iodinated contrast to produce cross-sectional images
of the arterial system, as well as imaging the adjacent non-vascular structures. For lower
extremity PAD, patients should be imaged from the renal arteries to the feet. Following
scanning, with modern computer techniques, the images produced can be displayed in a
variety of formats, from the more basic, axial, coronal, and sagittal planes to more advanced
3D reconstruction with soft tissue subtraction [34]. These techniques are continually
evolving.
MD-CTA has been extensively compared with DSA and the sensitivity and specificity of
detecting a 50% stenosis with MD-CTA, when compared with DSA, in two separate meta-
analysis is 92–95% and 93–96% respectively [36, 37].
Access to computer tomography scanning is now commonplace which makes acquisi-
tion of MD-CTA imaging increasingly straightforward. MD-CTA provides valuable ana-
tomical information regarding the vessel wall and surrounding tissues, which is a potential
limitation of predominantly luminal studies such as DSA. Examples include the identifica-
tion of peripheral aneurysms as well as specifying plaque characteristics, calcification,
ulceration, soft plaque or thrombus, neo-intimal hyperplasia, stent restenosis, and stent
fracture [38].
MD-CTA is useful for assessing the aorto-iliac segment, especially in patients where
body habitus or overlying bowel gas has made visualisation with CDUS difficult. The
higher resolution of MD-CTA can sometimes be useful for assessing the below knee vascu-
lature, however the presence of heavy calcification can make differentiation between con-
trast and calcification difficult and it is not recommended for the assessment of the below
knee vasculature in the diabetic patient [39].
The use of MD-CTA is accompanied by a dose of ionizing radiation and patient exposure
should be minimized where possible. Alongside this, the nephrotoxic iodinated contrast
dose used in MD-CTA is usually higher in comparison to DSA and may precipitate acute
kidney injury and need for dialysis. This should be considered when deciding upon imag-
ing modality for a given patient. An estimated glomerular filtration rate (eGFR) of >30 ml/
min is generally considered safe and pre and post scan hydration is recommended [40]. The
use of products such as sodium bicarbonate and acetylcysteine have not been shown to
reduce the rate of acute kidney injury or mortality [41].
500 30c Algorithms for Diabetic Foot Care

30c.3.3 Contrast Enhanced Magnetic Resonance Angiography (CE-MRA)

CE-MRA is a non-invasive imaging technique for PAD that has comparable sensitivity and
specificity to CDUS and MD-CTA [42]. During scanning two separate images are acquired;
firstly an unenhanced mask, followed by contrast enhanced images using gadolinium as the
paramagnetic contrast material,this makes it very susceptible to movement artefact. Its advan-
tages over MD-CTA and DSA include, less confusion between contrast and calcium, lack of
ionising radiation and gadolinium being less nephrotoxic than iodinated contrast [43].
Its limitations include limited spatial resolution, the potential for artefact, gadolinium
induced nephrogenic systemic fibrosis (NSF) in those with reduced eGFR (<30 ml/min)
[40] and the strict contraindications to its use including; implantable cardiac defibrillators,
cochlear implants, some stent grafts, aneurysm clips, and certain types of pacemaker.
Patients with claustrophobia may not tolerate the investigation where they must remain
still for lengthy periods of time to achieve adequate imaging.
It is essential to assess the below knee vessels and CE-MRA alone may suffer from venous
contamination. This is where contrast enters the venous system and confounds the image
obtained. To gain a high-level of accuracy in the assessment of these vessels a complex
hybrid CE-MRA technique must be used [44].

30c.3.4 Intra-Arterial Digital Subtraction Angiography

DSA is considered the gold standard for arterial imaging due to the high spatial resolution it
confers. It is especially useful for assessing vessels below the knee and the evaluation of pedal
circulation [45]. It has the advantage of providing real time imaging as well as allowing endo-
vascular intervention and revascularisation if required. However, the image obtained is two
dimensional and the potential complications are not insignificant. These include those relating
to arterial puncture, including haematoma, pseudoaneurysm, dissection, and limb ischaemia.
As well as those associated to contrast injection, including anaphylaxis and nephrotoxicity, par-
ticularly in those with pre-existing renal or cardiac failure [40]. Due to these risks, DSA is usu-
ally performed once the decision to revascularise has been made [4]. It is important to note that
MD-CTA, CE-MRA, and DSA only provide anatomical assessment and do not provide a physi-
ological assessment of perfusion and the need for revascularisation.

30c.3.5 Vascular Evaluation – Example Algorithms

What follows are suggested algorithms for the evaluation of the diabetic foot in the non-
ulcerated and ulcerated setting. There is no ‘optimum’ pathway and the choice of bedside
test and subsequent imaging relies upon the resources of the healthcare system and the
healthcare professionals requesting and reporting them.
Figures 30c.1 and 30c.2 are algorithms for the evaluation of the non-ulcerated and ulcer-
ated foot respectively.

30c.4 ­Conclusions

The detection of PAD in the intact foot in people with diabetes identifies a patient at
increased risk of subsequent ulceration and amputation.
 Annual History and Examination
(including palpation of pulses)
Symptomatic Patient:
Asymptomatic Patient: • Intermittent Claudication
• No Claudication • +/– Rest pain
• No Rest pain

Bedside Assessment:
Foot pulses
Bedside assessment
present? • Results mostly excluding PAD
1. Ankle brachial index of 0.9–1.3 Use a single test or in combination.
2. Toe brachial index of >0.75
Foot pulses present Foot pulses absent 3. Triphasic pedal Doppler arterial waveform • ABI
• TBI/Toe pressure
Remember in patients with diabetes ABI may be falsely • Triphasic ankle waveform
elevated, especially in patients with established • TcP02
neuropathy, as such more that one bedside test should • Skin Perfusion Pressure
be used.
Bedside assessment
• No further PAD Use a single test or in combination.
investigation. Bedside tests suggest PAD / perfusion deficit ? No
• Manage other risk • ABI
factors for ulceration • TBI / Toe pressure
(eg., neuropathy/callus) • Triphasic ankle waveform Rest Pain
• Diabetic foot education. • TcP02 • Consider vascular imaging
• Skin Perfusion Pressure and revascularisation • Risk factor modification
• Risk factor modification
Yes
and secondary
• Symptomatic control prevention
(analgesia / offload) • Lifestyle advice
No Bedside tests suggest PAD? • Consider alterative
diagnosis, e.g. diabetic
peripheral neuropathy,
Claudication
Yes spinal stenosis, Charcot
disease, arthritis.
• 1 Line :
Recommend lifestyle advice,
• High risk patient for the development of If at any point during the pathway the supervised exercise and
cardiovascualr risk factor
future diabetic foot ulceration. patient develops a foot ulcer switch to modification.
• Frequent review by the foot protection team.
• Patient made aware of likely underlying PAD.
the ulcer algorithm • 2 Line :
Consider revascularisation.
• Secondary cardiovascular prevention. (Figure 2)

Figure 30c.1 The intact foot (no ulceration).

 Bedside Assessment:
Foot ulcer identified Emergency management
• Investigations most likely to exclude PAD
1. ABI of 0.9–1.3 2. TBI of >0.75 3. Triphasic pedal Doppler arterial waveform
• Referral for sepsis control
• Predictors of successful ulcer healing • Needs urgent surgical
1. Toe pressure of >30mmHg 2. TCp02 >25mmHg 3. Skin perfusion pressure History and examination assessment to consider
>40mmHg (including palpation of pulses) debridement/drainage +/–
revascularisation.
• When to image and consider revascularisation with a foot ulcer
based on bedside test?
1. Toe pressure <30mmHg 2. TCP02 <25mmHg 3. ABI <0.5 or ankle pressure Are there signs of systemic sepsis/
<50 mmHg Yes
abscess/gangrene ?

Bedside assessment Bedside assessment

No
Use a single test or in combination. Use a single test or in combination.

• ABI • ABI
Foot pulses • TBI/Toe pressure
• TBI / Toe pressure No present?
Yes
• Triphasic ankle waveform • Triphasic ankle waveform
(no info on perfusion deficit) (no info on perfusion deficit)
• TcP02 • TcP02
• Skin Perfusion Pressure • Skin Perfusion Pressure

Bedside assessment suggests adequate Bedside assessment suggests adequate

Yes perfusion? perfusion?
Yes

Referral for vascular

Reasonable to manage
No imaging and consideration No
Reasonable to manage
conservatively for 6 weeks of revascularisation. conservatively for 6 weeks
with offloading and with offloading and
cardiovascular risk factor cardiovascular risk factor
modification modification

No signs of healing at 6 weeks or worsening despite best wound and medical therapy

Figure 30c.2 The ulcerated foot.

  ­Reference 503

PAD is highly prevalent in patients with diabetic foot ulceration. It is associated with
poor outcomes (failure to heal and amputation) and is therefore important to exclude.
History and clinical examination do not reliably exclude PAD. Non-invasive bedside tests
aid the detection and exclusion of PAD.
The decision to vascularize patients with a DFU and PAD is multifactorial. Those patients
with severe perfusion deficits are at greater risk of amputation and failure to heal. In this
group, vascular imaging should be undertaken to assess the morphological distribution of
PAD prior to consideration of revascularisation.

­References

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 507

30d

Algorithms for Diagnosis and Management of Infection

in the Diabetic Foot
Edgar J.G. Peters1 and Benjamin A. Lipsky2,3
1
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Internal Medicine, Amsterdam Infection & Immunity
Institute, Amsterdam, The Netherlands
2
Department of Medicine, University of Washington, Seattle, WA, USA
3
Green Templeton College, University of Oxford, Oxford, UK

30d.1 ­Diagnosis of Infection

For optimal management, clinicians should follow several steps in diagnosing and treating
patients with diabetes and a foot infection. Figure 30d.1 displays an algorithm giving an
overview of these steps. Beginning at the top of the figure, management begins with the
clinician having a clinical suspicion of the presence of a diabetic foot infection (DFI). Key
initial evaluations include assessment of the neurologic and vascular status of the affected
foot and efforts to optimize the patient’s metabolic status. The clinician should usually
debride the foot wound and at that time, if the wound is clinically infected, collect appro-
priate specimens for bacteriological evaluation. Non‐surgically trained clinicians should
consider the need for a surgical consult, especially for severe infections or those accompa-
nied by a deep abscess or extensive gangrene. Most patients with a severe DFI need surgery
at some point during their treatment.
In patients with an open wound, infection must be diagnosed clinically, not microbio-
logically. Clinically infected wounds should be categorised by their severity, as shown in
Table 30d.1. Persons with a clinically uninfected diabetic foot wound require appropriate
wound care, but not antimicrobial therapy. All patients with a clinically infected wound
should be assessed for anatomical depth of infection (superficial, tendon/muscle, joint/
bone). Classification of infection can help identify patients who might benefit from an
(initially) more aggressive approach, including in‐hospital treatment and surgery.
Furthermore, the recommended empiric antibiotic treatment differs amongst infection
classes. Detailed characteristics that suggest severe infection are mentioned in Figure 30d.1
and Table 30d.2.

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
 Person with diabetes with suspected foot infection

• Assess patient characteristics

- Neurological and vascular status
- Comorbidity and psycho-social status
• Assess wound characteristics
- Cleanse, debride and probe the wound
- Assess for purulence or signs of inflammation
- Consider plain radiographs
• Optimise glucose and metabolic status
• Obtain specimen(s) for microbiology
• Obtain other laboratory tests
• Determine if surgical consultation is needed
• Assess patient’s psycho-social situation

if clinically infected,
classify infection severity
Mild/moderate infection Severe infection

• Assess the need for inpatient treatment • Hospitalize the patient

• Review any available microbiological data • Attend to fluid, electrolyte, metabolic needs
• Arrange for surgery, if needed • Consider obtaining blood cultures
• Select initial antibiotic regimen (considering wound and patient characteristics) • Arrange for surgery, if needed
• Select appropriate wound care (dressings, off-loading) • Select empiric, broad-spectrum parenteral antibiotic regimen
• If treated as outpatient, set up return visit, consultations • Select appropriate wound care (debridement, dressings, off-loading)

Reassess in 2–4 days, or earlier if situation worsens no Hospitalized? yes

Reassess clinically at least once daily;

- Check inflammatory markers if needed
- Review culture and sensitivity results
no
Improving Not improving/worsening

Infection Consider de-escalating Not improving/worsening

Improving
cured? antibiotic regimen (narrower • Reassess need for surgery
spectrum, less toxic, less • Consider deep abscess, osteomyelitis
expensive) • Assess patient’s adherence to therapy • Reassess need for surgery, including abscess drainage,
yes revascularization, amputation
• Reassess wound care,
improvement • Reassess need for hospitalization • Switch to appropriate oral • Define extent of tissue involved (advanced imaging,
Worsening • Consider consultation of infectious antimicrobial regimen surgical exploration)
• Schedule first follow- diseases specialist or microbiologist • Consider follow-up as an • Consider consultation of infectious diseases specialist
up within 30 days Reassess, weekly
• Review microbiology results and outpatient or microbiologist
• Further patient until infection
change antibiotics accordingly • Ensure all identified isolates are optimally covered
education resolves
• Consider repeating obtaining wound • Consider broadening antibiotic spectrum
• Regular follow-up specimens

Figure 30d.1 Suggested overview of a stepwise approach to managing a patient with diabetes and a suspected foot infection (https://
iwgdfguidelines.org/wp-content/uploads/2019/05/05-IWGDF-infection-guideline-2019.pdf)
 30d.2 ­Therapy of Infectio 509

Table 30d.1 IDSA and IWGDF (PEDIS) classification on diabetic foot infection [1–3].

IWGDF IDSA infection

grade severity Clinical manifestation of infection

1 Uninfected No symptoms or signs of infection

2 Mild
Infection involving the skin and the subcutaneous tissue only
(without involvement of deeper tissues and without systemic signs,
as described below), defined by the presence of ≥2 of the
following:
●● Local swelling or induration

●● Erythema of >0.5 but ≤2 cm around the ulcer

●● Local tenderness or pain

●● Local warmth

●● Purulent discharge (thick, opaque to white or sanguineous

secretion)

Exclude other causes of an inflammatory response of the skin are

(e.g., trauma, gout, acute Charcot neuro‐osteoarthropathy, fracture,
thrombosis, venous stasis)
3 Moderate Erythema >2 cm plus one of the items described above (swelling,
tenderness, warmth, discharge), or

Infection involving structures deeper than skin and subcutaneous

tissues, such as abscess, septic arthritis, fasciitis.

No systemic inflammatory response signs, as described below

4 Severe
Any foot infection with signs of a systemic inflammatory response
syndrome (SIRS), manifested by ≥2 of the following:
Temperature > 38 or < 36 °C
Heart rate > 90 beats/min
Respiratory rate > 20 breaths/min or PaCO2 < 4.3 kPa (32 mmHg)
White blood cell count >12 000 or <
4000 cu/mm or ≥10% immature (band) forms

The presence of osteomyelitis [5] in a patient with a moderate or

severe infection is designated by having (O) after the severity class.

(IDSA = Infectious Diseases Society of America, IWGDF = International Working Group on the Diabetic
Foot, PEDIS is an acronym for perfusion, extent, depth, infection and sensation)

30d.2 ­Therapy of Infection

After initiating treatment, patients with a foot infection need to be re‐evalutated frequently
to assess its success. If signs and symptoms of a DFI are not resolving, the clinician should
reconsider first the diagnosis, then the selected treatment. This should include re‐­examining
the wound, but might also entail ordering new studies (e.g., more advanced imaging tech-
niques), or consulting an infectious diseases specialist or microbiologist. If the patient
improves, the clinician can consider de‐escalating therapy (e.g., narrowing the antibiotic
510 30d Algorithms for Diagnosis and Management of Infection in the Diabetic Foot

Table 30d.2 Characteristics suggesting a severe diabetic foot infection and indications
for hospitalization and possibly early surgery.

A – Findings suggesting severe diabetic foot infection

Wound specific

Wound Penetrates to subcutaneous tissues

Cellulitis Rapidly progressive, or >2 cm distance from ulceration
Local signs Severe inflammation or induration, crepitus, bullae, discoloration, necrosis,
ecchymosis or petechiae, new anaesthesia or new pain in a person with severe
neuropathy

General

Systemic signs Fever, chills, hypotension, confusion, volume depletion

Laboratory tests Leucocytosis, very high C‐reactive protein or erythrocyte sedimentation
rate, unexplained hyperglycemia, acidosis, new azotemia, electrolyte
abnormalities
Complicating Presence of a foreign body, puncture wound, deep abscess, arterial, or venous
features insufficiency, lymphedema, immunosuppressive host
Current Progression while on apparently appropriate therapy
treatment

B – Factors suggesting hospitalization may be necessary

●● Severe infection (See Table 30d.1) (with metabolic or hemodynamic instability)

●● Intravenous therapy needed (and not available as outpatient)
●● Diagnostic tests needed (if not available as outpatient)
●● Critical foot ischemia present
●● Surgical procedures (more than minor) required
●● Failure of outpatient management
●● Patient unable or unwilling to adhere to outpatient‐based treatment
●● Need for more complex dressing changes than patient/caregivers can provide
●● Need for continuous observation

Source: modified from [1].

spectrum, switching from parenteral to oral antibiotics, arranging hospital discharge,

increasing the time between follow‐up assessments).
Factors that suggest severe disease, likely leading to hospitalization and surgery, are sum-
marised in Table 30d.2. A clinician should strongly consider consulting a surgeon if find-
ings listed in Table 30d.2A that suggest serious infection are noted, e.g., metabolic instability,
presence of an abscess, infected necrosis, osteomyelitis or septic arthritis, or evidence of the
systemic inflammatory response syndrome (Table 30d.1).
 30d.2 ­Therapy of Infectio 511

Table 30d.3 Questions a clinician should consider before choosing an empiric

antibiotic regimen.

●● Is there clinical evidence of infection?

–– If no, do not treat with antibiotics
–– If yes, follow steps shown in Figure 30d.1 and consider the questions below.
●● Is the infection classified as severe or moderate?
–– If no, consider only treating with agents active against streptococci and Staphylococcus
aureus
–– If yes, consider including coverage for commonly pathogenic gram‐negative bacilli
●● Is there high risk of MRSA (e.g., based on epidemiologic factors or local prevalence)
–– If no, do not empirically treat for MRSA
–– If yes, include an empiric antibiotic regimen that covers MRSA if the risk of MRSA is high
●● Has patient received antibiotic therapy in the past month?
–– If no, agents targeted only at streptococci and S. aureus may suffice
–– If yes, include agents active against gram‐negative bacilli
●● Are there risk factors for Pseudomonas aeruginosa infection?a
–– If no, empiric antipseudomonal treatment is rarely needed
–– If yes, consider empiric antipseudomonal agent
●● Are there risk factors for infection with obligate anaerobes (e.g., limb ischemia, extensive
gangrene, foul odor)
–– If no, no need for an anti‐anaerobic antibiotic regimen
–– If yes, consider an empiric antibiotic regimen that covers anaerobic bacteria
●● What is the infection severity status?
–– Severe infections should be initially treated with a broader‐spectrum antimicrobial regimen

Abbreviation: MRSA = methicillin‐resistant Staphylococcus aureus.

See Table 30d.4 for suggested regimens for mild versus moderate/severe infections.
a
Such as high local prevalence of Pseudomonas infection, warm climate, frequent exposure of the foot
to water.

An empiric regimen is antibiotic therapy administered before culture results

(and therefore the causative pathogens and their antibiotic sensitivities) are available.
At the beginning of treatment, especially in moderate and severe infection, the bacterial
load is high and the chance of limb loss is substantial. Thus, the spectrum of therapy
should be broad enough to cover all important pathogens, but not commensals or colo-
nizing flora. Empiric therapy should be modified, preferably to a narrower spectrum
regimen, when culture and sensitivity results are available, and based on the clinical
response. Guidance on how to choose an empiric antibiotic treatment can be found in
Tables 30d.3 and 30d.4.
If osteomyelitis is present, it is often treated with surgical resection of infected and
necrotic bone, combined with systemic antibiotic therapy. Selected patients with osteomy-
elitis can be treated with antibiotics alone, without surgery. Guidance on how to choose
between the two treatment modalities is given in Table 30d.5.
Table 30d.4 Suggestions for empiric antibiotic regimens based on the IDSA guidelines [2].
Infection severity
Mild (usually treated with
oral antibiotics
Moderate (oral or intial
parenteral antibiotics) or
severe (usually treated
with parenteral antibiotics)
Likely pathogen Antimicrobial agent Comment
S. aureus (MSSA), Dicloxacillin or flucloxacillin QID dosing, narrow spectrum, inexpensive
Streptococcus spp. Clindamycin Usually active against community acquired MRSA, consider
ordering a D‐test before using for MRSA. Inhibits protein
synthesis of some toxins
Cephalexin QID dosing, inexpensive
Levofloxacin Once‐daily dosing, suboptimal against S. aureus
Amoxicillin/clavulanate Relatively broad‐spectrum oral agent, includes anaerobic
coverage
MRSA Doxycycline Active against many MRSA and some gram‐negative
organisms, uncertain against Streptococcus spp.
Trimethoprim/ Active against MRSA and some gram‐negatives. Uncertain
sulfamethoxazole activity against Streptococcus spp.
MSSA, Streptococcus spp., Levofloxacin Once‐daily dosing, suboptimal against S. aureus
Enterobacteriaceae, Cefoxitin Second‐generation cephalosporin with anaerobic coverage
obligate anaerobes
Ceftriaxone Once‐daily dosing, third generation cephalosporin
Ampicillin‐sulbactam Adequate if low suspicion of P. aeruginosa
Moxifloxacin Once‐daily oral dosing. Relatively broad‐spectrum, including
most
obligate anaerobic organisms
Ertapenem Once‐daily dosing. Relatively broad‐spectrum including
anaerobes, but not active against P. aeruginosa
Tigecycline Active against MRSA. Spectrum may be excessively broad. High
rates of nausea and vomiting and increased mortality warning.
Levofloxacin or ciprofloxacin Limited evidence supporting clindamycin for severe S. aureus
with clindamycin infections; PO & IV formulations for both drugs
 Imipenem‐cilastatin Very broad‐spectrum (but not against MRSA); use only when
this is required. Consider when ESBL‐producing pathogens
suspected
MRSA Linezolid Expensive; increased risk of toxicities when used >2 wk.
Daptomycin Once‐daily dosing. Requires serial monitoring of CPK
Vancomycin Vancomycin MICs for MRSA are
gradually increasing
Pseudomonas Piperacillin‐tazobactam TID/QID dosing. Useful for broad‐spectrum coverage.
aeruginosa P. aeruginosa is an uncommon pathogen in diabetic foot
infections except in special circumstances
MRSA, Vancomycina, ceftazidime, Very broad‐spectrum coverage. Usually only used for empiric
Enterobacteriacae, cefepime, piperacillin/ therapy of severe infection. Consider addition of obligate
Pseudomonas, and tazobactam, anaerobe coverage if ceftazidime,
obligate anaerobes aztreonam, or a carbapenem cefepime, or aztreonam selected

Abbreviations: CPK, creatine phosphokinase; ESBL, extended‐spectrum β‐lactamase; FDA, US Food and Drug Administration; IV, intravenous; MIC, minimum inhibitory
concentration; MRSA, methicillin‐resistant S. aureus; MSSA, methicillin‐sensitive S. aureus; PO, oral; QID, 4 times a day; TID, 3 times a day.
Narrow‐spectrum agents (e.g. vancomycin, linezolid, daptomycin) should be combined with other agents (e.g. a fluoroquinolone) if a polymicrobial infection (especially
moderate or severe) is suspected.
Use an agent active against MRSA for patients who have a severe infection, evidence of infection or colonisation with this organism elsewhere, or epidemiological risk
factors for MRSA infection.
Select definitive regimens after considering the results of culture and susceptibility tests from wound specimens, as well as the clinical response to the empiric regimen.
Similar agents of the same drug class can probably be substituted for suggested agents.
Some of these regimens do not have FDA approval for complicated skin and skin structure infections.
a
Daptomycin or linezolid may be substituted for vancomycin.
514 30d Algorithms for Diagnosis and Management of Infection in the Diabetic Foot

Table 30d.5 For treating diabetic foot osteomyelitis, factors favoring either primarily antibiotic or
primarily surgical resection.

Favoring medical treatment

●● Patient’s medical history or metabolic status poses high surgical risk

●● Poor postoperative mechanics anticipated (e.g. mid‐ or hind‐foot infection)
●● No other surgical procedures on the foot are needed
●● Infection is confined to small, forefoot lesion
●● No adequately skilled surgeon is available
●● Surgery costs are prohibitive for the patient
●● Patient has a strong preference to avoid surgery

Favoring surgical treatment

●● Foot infection is associated with substantial bone necrosis or exposed joint

●● Foot appears to be functionally non‐salvageable
●● Patient is already non‐ambulatory
●● Patient is at particularly high risk for antibiotic‐related problems
●● Infecting pathogen is resistant to available antibiotics
●● Limb has uncorrectable ischemia (precluding systemic antibiotic delivery or leading to
intractable pain)
●● Patient has a strong preference for surgical treatment

Source: modified from [1, 4].

­References

1 Lipsky, B.A., Aragon‐Sanchez, J., Diggle, M. et al. (2016). IWGDF guidance on the diagnosis
and management of foot infections in persons with diabetes. Diabetes Metab. Res. Rev. 32
(Suppl 1): 45–74. https://doi.org/10.1002/dmrr.2699.
2 Lipsky, B.A., Berendt, A.R., Cornia, P.B. et al. (2012). Infectious Diseases Society of America
clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin.
Infect. Dis. 54 (12): e132–e173. https://doi.org/10.1093/cid/cis346.
3 Schaper, N.C. (2004). Diabetic foot ulcer classification system for research purposes: a
progress report on criteria for including patients in research studies. Diabetes Metab. Res. 20
(Suppl 1): 90–95.
4 Lipsky, B.A. (2014). Treating diabetic foot osteomyelitis primarily with surgery or antibiotics:
have we answered the question? Diabetes Care 37 (3): 593–595. https://doi.org/10.2337/
dc13‐2510.
5 Berendt, A.R., Peters, E.J., Bakker, K. et al. (2008). Diabetic foot osteomyelitis: a progress report
on diagnosis and a systematic review of treatment. Diabetes Metab. Res. Rev. 24 (Suppl 1):
S145–S161.
 515

Index

Page numbers in bold indicate tables or boxes; page numbers in italic indicate figures.

21 point checklist, clinical trial Albania 71

assessment 231–3 Alexa Diabetes Challenge 217
alginates, dressings 308
a algorithms 475–512
AASD see Asian Association for the Study of diabetic foot infection 505–12
Diabetes diabetic foot ulcer 479–91
abdominal pain 96 hot swollen foot 475–8
ABI see ankle brachial index peripheral arterial disease 493–504
ABPI see ankle brachial pressure index reconstructive surgery 461–2
abscesses, apparent diffusion vascular assessment 498, 499, 500
coefficient 180–1 allograft skin 242, 464
accessory ossicle 166 alpha‐lipoic acid, neuropathic pain
access to healthcare 25, 37 management 100
acellular wound care products 308 alternative medicine 80
Achilles tendon lengthening 129, 299, 336, Amazon (company) 217
337, 357, 385–6, 404, 413 American Samoa 87
Achilles tendon moment arm, internal 191 amitriptyline 99
acute painful neuropathies 94–5 amoxicillin 270, 274
adipose‐derived stems cells (ASCs) 441, ampicillin‐sulbactam 270
443, 444, 449–50 amputation 31–41, 347–64
adipose tissue, injection into plantar Achilles tendon lengthening 357
foot 413 ankle disarticulation 351, 357, 358–9, 360
administrative staff, diabetic foot clinics 427 in Australia 85
adverse events 231 bone spike projection 158
aerobic exercise 196, 198 in Brazil 62
AFO see ankle foot orthoses and Charcot foot 325, 337
Africa see Sub‐Saharan Africa costs and benefits 21, 24
African Americans, diabetes‐related counselling of patients 44–5
amputation risk 37 in Czech Republic 70
age, DFU risk 109 data collection 432–3

The Foot in Diabetes, Fifth Edition. Edited by Andrew J. M. Boulton, Gerry Rayman, and Dane K. Wukich.
© 2020 John Wiley & Sons Ltd. Published 2020 by John Wiley & Sons Ltd.
516 Index
amputation (cont’d)
decision to perform 433
definition of 32
and diabetic foot infection 289, 290
direct load transfer 351
elective amputation 337
end‐bearing disarticulation 350
epidemiology of 31
EQ‐5D score 19
ethnic differences 35–8, 36
financial costs of 21, 24
flap types 354, 357, 358, 360, 361, 362
foot amputation, prosthetics 366–8
hallux (great toe) amputation 354–5, 379
orthotics 367
prevention of 380
hindfoot amputation 357, 359
in Hungary 70
incidence of 7, 17, 31, 433
global variation 34, 36
study design 32
variation within countries 431
incisions 358
in India 43–4
indirect load transfer 352
international differences 34, 36
knee disarticulation 350, 351, 361
prosthetics 371–2
lesser toe amputation 355, 356
levels of 350, 354–62
limb salvage versus amputation 238–9,
349–50, 377
load transfer in 350–2
‘lower extremity amputation’ term 432
‘major LEA’ definition 32
metabolic cost of walking with an
amputation 348–9
midfoot amputation 357, 358
minor amputation 17, 24, 32, 146
mortality rates 31, 201, 459
mortality risk 7–8, 20, 239
nerve transection 354
in New Zealand 86
open wound management 353
for osteomyelitis 388
outcomes 354
in Pakistan 47, 48
patient fear of 9
patient health status 146
phantom‐limb pain 353–4
plantar pressure elevation 129
post‐Charcot foot reconstruction 337
prevalence of 7, 17
prevention strategies 10
principles of 365
prosthetics 365–76
proximal foot amputation 368
psychological impact of 347–8
quality of life impact 347, 348
rates of 24, 34–5
ray resection 355–7, 367
reconstructive surgery role 468
regional differences 34
rehabilitation of amputee 365–76
impediments to 347–8
residual limb pain 354
risk assessment study design 32–3
risk factors 1, 6–7, 33–8, 43–4
ethnic differences 35–8, 36
non‐clinical factors 33–8
in Romania 68, 69
soft tissue envelope 350, 352, 353, 357
staged surgery 353
in Sub‐Saharan Africa 56
survival rates 8
Syme’s ankle disarticulation amputation
357, 358–9, 360
‘terminal Syme’s amputation’ 354
time trends data 34–5
tissue management 353–4
transfemoral amputation 352, 361–2
prosthetics 372
transmetatarsal amputation, orthotics 367–8
transtibial amputation 299–300, 337, 352,
359–61
prosthetics 368–70
in UK 105, 261, 479
in US 365, 441, 479
versus limb salvage 238–9, 349–50, 377
weight‐bearing in 350–2
amyotrophy 95–6
anaerobes 269, 270, 271, 274

anastomosis, reconstructive
microsurgery 467
anatomic tunnelling, bypass surgery 242
angiogenesis 446, 449
angiography 157, 236, 237, 240, 248, 250,
463, 497, 498
angioplasty
endovascular 463
tibial artery 251, 252, 253–4
angiosomes, of foot and ankle 293–4, 462
ankle
disarticulation 351, 357, 358–9, 360
realignment arthrodesis 334
soft tissue oedema 171, 180
ankle brachial index (ABI) 175, 248, 249,
290, 296, 329, 494–5
ankle brachial pressure index (ABPI)
228, 482
ankle Doppler signal, PAD diagnosis 495
ankle foot orthoses (AFO) 357, 367, 368
ankle‐foot prosthetics 371–3
ankle joint, biomechanics during
walking 191–2
annual reviews, for diabetic patients
112–14
antibiotic‐impregnated cement spacer 390
antibiotic pellets 160, 161
antibiotic‐resistant bacteria 269, 485–6
antibiotic treatment 272–4, 291, 477, 485–7
comparison of antibiotics 273
considerations for clinician 509
duration of 274, 280–1, 487
empiric therapy 270–1, 509
nurses’ role 422
osteomyelitis 278, 280–1
outpatient parenteral antibiotic
therapy 427
PEDIS Grade 2 (mild) infections 273–4
PEDIS Grade 3 (moderate) infections 274
PEDIS Grade 4 (severe) infections 274–5
selection of 269
topical treatments 274, 275
of uninfected ulcers 272
versus surgical treatment 512
anticonvulsants, neuropathic pain
management 99
Index 517
antidepressants, tricyclic, neuropathic pain
management 99
antiseptics, wound healing 307
apparent diffusion coefficient (ADC), MRI
scans 179–81, 182
apps
foot monitoring 205, 210
wound tracking 215–16
area under receiver operating characteristic
curves (AUROC) 2
arterial lesions 248
arteriograms 251
arthrodesis, midfoot realignment 176,
331–4, 333, 337
ASCs see adipose‐derived stems cells
Asian Association for the Study of Diabetes
(AASD) 76
Asians, British see Indian Asians, UK
Association for Podiatry 69
asymmetrical neuropathies 95–7
atherosclerosis 247, 248
athletes, pedal fracture 158
athletic shoes 131
audit of foot care see clinical audit of
foot care
AUROC see area under receiver operating
characteristic curves
Australia, diabetic foot disease 85–6, 87
Austria, diabetic foot ulcer, medical costs
of 9–10
autolytic debridement 307
axial screw fixation, CN midfoot 332–3
aztreonam 271
b
balance
centre of mass to centre of pressure
separation 194–5
during gait 194–6
exercise effects 197–8
impairment
diabetic neuropathy 109, 144–5
patient perceptions of 148
therapeutic footwear 407
wearable technologies 203–4
balloon angioplasty 251, 252
518 Index
bandaging, compression 304
see also dressings
Barbados, inpatient beds for diabetic foot
disease 260
barefoot plantar pressure 412
barefoot walking, plantar ulceration
risk 130
BASIL see Bypass versus Angioplasty in
Severe Ischemia of the Leg trial
behavioural factors 139–51
DFU development 139–42
DFU healing 142–5
DFU impact on patient health
status 146–7
quality of life in DFU patients 147–8
below knee amputation (BKA) see transtibial
amputation
Benin, PAD prevalence 54
Bentson wire 250
bespoke shoes 405, 406
beta‐lactam 274
bias, amputation incidence study 32
Biobrane (skin substitute) 464
biochemistry, DFU diagnosis 481
bioengineered products, wound healing 464
biofilm 276
bioinformatics analysis 448
biomechanics 125–37
barefoot walking 130
effective mechanical advantage 191, 192
fall risk 193
of gait 188–92
ground reaction force 191
muscle atrophy 129
plantar pressure elevation and foot
ulceration 126–8
prevention of DFU 132–3
treatment of DFU 130–2
biothesiometers 44
bivalved total contact casts 131
BKA (below knee amputation) see transtibial
amputation
BM see bone marrow
BM‐MPCs see bone marrow‐derived
mesenchymal progenitor cells
bone biopsy 278, 316–17
bone demineralization 160, 161
bone erosions 165
bone marrow (BM), neovascularization 446
bone marrow‐derived mesenchymal
progenitor cells (BM‐MPCs) 445, 447
bone marrow‐derived stem cells 451
bone marrow oedema 172, 174
MRI scans 180, 182
bone necrosis 353
bone resorption 164, 316–17
bone scans 180, 182, 277
bone specimens, cultures of 269
bone spike, post‐amputation 158
bony prominences
normal anatomy 165, 166
plantar pressure elevation 125–6, 127
Brand, Paul 111, 126
Brazil 61–5
Brazupa Study 62, 63
costs of diabetic foot disease/treatment
9, 261
Step by Step training courses 64
breast cancer 18, 19
Brodsky Anatomic Classification of Charcot
arthropathy 327
Bulgaria 71
bunion (hallux valgus) 92, 111, 355, 356
Burgess, Ernest 347
Burkina Faso 55
bypass surgery 235–45, 275, 463
benefit/risk assessment 237–9
communication with patient 239
distal ‘target’ vessels 239–40
effectiveness of 237
with endovascular revascularization
252, 254
endovascular revascularization
comparison 253
follow‐up after operation 243
frail, marginal patients 238–9
graft tunnelling 242
in‐hospital recovery 242–3
mortality rate 237
operation procedure 241–2

PAD identification in diabetes patients
235–7
patients with no limb function 238
rehabilitation potential 238
risk/benefit assessment 237–9
surgeon communication with patient 239
‘target’ vessels 239–40
technique 241–2
vascular anatomy evaluation 239–41
venous conduit 240–2
wound healing 242, 243
Bypass versus Angioplasty in Severe Ischemia
of the Leg (BASIL) trial 253, 254
c cephalosporin 273
cadaver skin (allograft) 242, 464
CAD‐CAM see computer‐aided
manufacturing system
calcanectomy 298, 391
calcaneum, ‘open beak’ fracture 158–60
calcification, vascular 157, 162
calcitonin gene‐related peptide (CGRP) 315
calluses, ulceration risk 111, 119, 127, 128
CAM see complementary or alternative
medicine
Cameroon
health outcomes for diabetes
population 55
PAD prevalence 54
peripheral neuropathy prevalence 53
carbapenem 271, 274
care pathways 25, 435, 436, 488–9
care principles 420
care quality 23
care standards 230
Caribbean, amputation incidence 37–8
carpal tunnel release 97
case reports/series 226
cast walkers 130, 131, 145, 214, 319, 320,
336, 385–6, 485
cautery 80
CCGs see Clinical Commissioning Groups
cDNA see complementary DNA
CDUS see colour Doppler ultrasound
cefepime 271
Index 519
cefoxitin 270
ceftazidime 271
ceftriaxone 270
cell phones 215
see also smartphones
cellulitis 319
cellultic foot 475, 476–7
cement spacer, antibiotic‐impregnated 390
CE‐MRA see contrast‐enhanced magnetic
resonance angiography
central nervous system (CNS), diabetic
neuropathy 97–8
central ray resection 356–7
cephalexin 270
CGRP see calcitonin gene‐related peptide
Charcot fractures, plantar pressure elevation
128–9
Charcot neuroarthropathy (CN) (Charcot
foot) 139, 170, 313–23, 419–20
Achilles tendon lengthening 336, 337
acute management of 318–20
amputation risk 325
bone marrow oedema 172, 174, 177
bone resorption and inflammation link
316–17
Brodsky Anatomic Classification 327
clinical impact of neuropathy on
bone 314
clinical presentation 318–19
diagnosis 319
foot deformity 318, 326, 327, 328
footwear 406
fractures, plantar pressure elevation
128–9
gastrocnemius recession 299, 336
genetic factors 317–18
glycaemic control 329–30
histological analysis, bone specimens
316–17
inflammatory response to trauma 315–16
investigations and diagnosis 319
midfoot breakdown 333
midfoot deformities 327, 328
MRI scans 174, 177, 177, 178, 179
520 Index
Charcot neuroarthropathy (CN) (Charcot
foot) (cont’d)
negative cuboid height 328
neuropeptides 315
nonplantigrade deformity 326
non‐surgical interventions 176
offloading treatment 319–20
osteoclast activation 316
pathogenesis of 313–18
theories 313–14
patient health status 146
pharmacological therapies 320
plantar ulceration 326
post‐operative management 336
preoperative medical workup 329
prevalence of in diabetic patients 325
radiographs 156, 157, 162–4, 172, 173,
174, 319, 326, 327–8
renal disease/impairment 330
Sanders and Frykberg Anatomic
Classification 327
serial radiography 156, 157
surgical reconstruction 176, 325–46, 413
Achilles tendon lengthening 336, 337
amputation rate 337
ancillary procedures 336
exostectomy 330–1, 337
fixation methods 337–8
glycaemic control assessment 329–30
hindfoot and ankle 334
indications for 325–6
internal/external fixation 334–6, 337–8
midfoot deformity correction 326,
331–3
outcomes 330–7
PAD assessment 329
post‐operative management 336
procedures 330–6
realignment arthrodesis 331–4, 333, 337
recommendations 337–8
renal function 330
timing of surgery 328–9, 337
Vitamin D deficiency 330
talonavicular and subtalar dislocation 326
trauma response 315–16
treatment 319–20
unilateral foot swelling 318
Vitamin D deficiency 330
see also diabetic neuropathy
Charcot restraint orthotic walker
(CROW) 391
checklists, clinical trial assessment 231–3
China 75
chiropodists 81
chronic limb‐threatening ischemia (CLTI)
235, 237, 238
chronic obstructive pulmonary disease
(COPD) 18, 19
chronic wounds, healing therapies 308–9
ciprofloxacin 271
claw toes 92, 119, 128, 413
cleaning of wound see debridement
clerical staff, diabetic foot clinics 427
CLI see critical limb ischemia
clindamycin 270, 273, 274, 280
clinical audit of foot care 431–40
new ulceration onset 435
outcome measures 432–4
populations, definition of 434
principles of 432–5
purpose of 431–2
wound healing 434–5
Clinical Commissioning Groups (CCGs)
24, 436
clinical outcomes see health outcomes
clinical trials, assessment of 225–34
21 point checklist 231–3
adverse events 231
diabetic person, features of 228
foot, features of 228
guidelines 225–6
hierarchy of evidence 226–7
intervention/therapy description 230
limb, features of 228
limb outcomes 231
person outcomes 230
population factors 227–8
scoring systems 225
ulcer, features of 229
ulcer‐related outcomes 231
 Index 521

clinics see diabetic foot clinics in India 43

clopidogrel 250
CLTI see chronic limb‐threatening ischemia
cluster analyses 142
CN see Charcot neuroarthropathy
CNS see central nervous system
coamoxiclav 486
Cochrane reviews
antibiotic therapy for DFI 273
patient education 487
cognitive impairment 487
collagenases, topical, wound cleaning 307
collagen bilayer matrix, wound closure 297
colloid imaging 177
colour Doppler ultrasound (CDUS) 496–7
Common Sense Model (CSM), illness
behaviour 141, 142
communication with patient, surgeons 239
comorbidities, DFU management 487
complementary or alternative medicine
(CAM) 80
complementary DNA (cDNA) 448
computed tomography (CT) 153–4, 175–7
advantages/disadvantages of 175–6
multidetector‐row computed tomography
angiography 497
osteomyelitis 176
single photon emission computed
tomography 172–3
computer‐aided manufacturing (CAD‐CAM)
system 367
computerized radiography (CR) 154, 155
contrast‐enhanced magnetic resonance
angiography (CE‐MRA) 498
COPD see chronic obstructive pulmonary
disease
cost‐effectiveness
DFU and amputation prevention 10
EQ‐5D instrument 19
healthcare interventions 23–5
limitations of 24–5
costs of diabetic foot disease/treatment
9–10, 22, 24, 106, 303, 479
in Brazil 62, 261
global cost 201, 202
in UK 17–29, 225
in US 170, 225
see also delayed presentations
Cote d’Ivoire see Ivory Coast
counselling 44–5, 354, 414–15
country/region perspectives
Australasia 85–8
Brazil 9, 61–5
China 75
Eastern Europe 67–73
India 43–5, 57
Middle East 79–83
Pacific region 75–7, 86–7
Pakistan 47–9
Romania 67–9
see also Sub‐Saharan Africa; United
Kingdom; United States
CR see computerized radiography
cranial nerve palsies 96
creams, moisturizing 81
critical limb ischemia (CLI) 237, 482
CROW see Charcot restraint orthotic walker
CSM see Common Sense Model
CT see computed tomography
cuff suspension 370
cultural values 80
cushioning, footwear 399
custom‐made footwear 133, 405, 406
cysts, fsT2W imaging 179
cytokines 316
Czech Republic 70
d
daptomycin 271
DARTS study (Diabetes Audit and Research
in Tayside Scotland) 106
data collection
on amputation 432–3
DFUs in England and Wales 436–7
information reliability 433
for National Diabetes Foot Care Audit of
England and Wales 435
principle of 434
DDR see direct digital radiography
522 Index

death see mortality diabetic foot care assistants (DFCAs) 47

debridement 294, 295, 296, 297, 306–7, diabetic foot clinics 204, 419–29
462–3 administrative staff 427
larval debridement 275, 280, 307, 483 care principles 420
deformities see foot deformities dermatologists 424
delayed presentations 52, 68 DFU investigations 481
‘dental’ imaging plates 154–5 diabetologists 422
depression emergency patients 425
and amputation 348 in‐patient care 427
and DFU healing 142–3 interventional radiologists 423
DFU incidence and 140–1 joint specialist clinics 425–6, 427
and DFU risk 147–8 leadership 428
predictors of 144–5 location of 420
dermal substitutes see skin grafts/substitutes microbiologists 423–4
dermatological examination 290 multidisciplinary teams 425–6
dermatologists 424 multidisciplinary vascular radiology
developing countries meetings 426–7
diabetes in 43 nurses 422
diagnosis of high risk feet 44 occupational therapists 424
see also individual countries open access service 425
DFA see Diabetic Foot Australia organisation of 424–8
DFCAs see diabetic foot care assistants orthopaedic clinics 426
DFD see diabetic foot disease orthopaedic surgeons 423
DFI see diabetic foot infection orthotists 422
DFO (diabetic foot osteomyelitis) see outpatient parenteral antibiotic therapy 427
osteomyelitis personnel for 421–4
DFS see Diabetic Foot Ulcer Scale pharmacists 424
DFU see diabetic foot ulcer physiotherapists 424
Diabetes Audit and Research in Tayside plastic clinics 427
Scotland (DARTS) study 106 plastic surgeons 423
diabetes mellitus (DM) podiatrists 421–2
diagnosis miscoding 32 psychiatrists 424
duration of, and DFU risk 109 radiologists 423
incidence/prevalence 32, 47, 433 reception staff 427
global 31, 201, 202 space for 420–1
in US 169, 441 vascular clinics 426
infection pathophysiology in diabetic vascular scientists 423
persons 265–6 vascular surgeons 423
with macrovascular complications, EQ‐5D diabetic foot disease (DFD)
score 19 burden of inpatient DFD 260–1
risk factors 169 in Middle East 79–80
type 1 and type 2 differentiation issue 32 natural history of 419–20
under‐reporting of 32 pathophysiology of 170
Diabetes UK 261 risk assessment 93
Diabetic Foot Australia (DFA) 86 surgery for 377–95

diabetic foot infection (DFI) 265–87
algorithms 505–12
amputation risk 289, 290
antibiotic treatment 269, 270–1, 272–4,
291, 509
classification of 267, 268, 291, 505, 507
clinical signs and symptoms 266–8
clinical trial assessment 229
dermatological examination 290
diagnosis 266, 267, 505, 506, 507
examination 290–1
hospitalization requirement 508
hyperbaric oxygen therapy 275
IDSA classification 507
incidence of 265
infection pathophysiology 265–6
infectious disease consultation 296
and kidney function 44
microbiological analysis 268–72
musculoskeletal examination 290–1
neurological examination 290
offloading treatment 298
PEDIS classification 267, 507
plastic surgery consultation 296
quality of life impact 289
radiographic evaluation 291
revascularization 275
risk factors 266
severity of 508
soft tissue/tendon balancing 299
in Sub‐Saharan Africa 55–6
surgery 289–302
debridement 294, 295, 296, 297
infection tracking 294
initial intervention 292
irrigation 295
offloading treatment 298
osseous reconstruction 298–9
proximal level amputation decision
299–300
tissue viability, colour guide 294
vascular surgery consultation 295–6
wound closure techniques 296–8
symptoms 266–8
treatment 507–12
Index 523
vascular examination 290
white blood cell count 176, 177
see also osteomyelitis
Diabetic Foot International 439
diabetic foot osteomyelitis (DFO) see
osteomyelitis
diabetic foot ulcer (DFU) 479–91
age of patient 109
area and depth 229
assessment 480–2, 484
in Australasia 87
behavioural factors 139–51
biomechanics 125–37
in Brazil 61, 62
causation 116, 117
Charcot foot 326
classification of 2–3, 6, 9–10, 434, 482
clinical care 480–3
clinical trial assessment 229
comorbidities management 487
component cause 116, 117
definition of 1–2
and depression 140–1, 142–5
and diabetes duration 109
and diabetic neuropathy 107–9
dressings 303–11
duration of at first assessment 436, 437
economic impact 9–10
emotional factors 147
epidemiology 1–9
EQ‐5D score 19
ethnic differences 35, 110
financial cost 9–10, 25, 62, 303
footwear reviews 482
healing of 2, 6, 132, 142–3, 145,
303, 305
health centred outcomes 7–8
hemorrhagic callus, examination for 414
hospitalization 4, 5, 7
imaging studies 180, 481, 482–3
incidence of 3–5, 17–18, 25, 61, 201, 479
infection identification 480–1
initial assessment 484
ischemic DFU 481
location for ulcer 2–3
524 Index
diabetic foot ulcer (DFU) (cont’d)
management of 215–17, 483–9
clinical care 480–3
dressings 303–11
effectiveness measurement 431–40
overview 486
structural care process 488–9
mechanical factors 118–20, 484–5
medical cost 9–10, 25, 62, 303
metabolic control 487
microbiological control 485–7
microvascular complications 110
mortality risk 7–8, 20, 479
MRI scans 180
multidisciplinary treatment 10
neuroischemic ulcers 419, 463, 482
neuropathic ulcers 463
in New Zealand 86
non‐healing ulcers 449
outcomes 7–9
and PAD 106–7
pathogenesis 105–11
pathophysiology 52
pathways to 107, 116–17
patient assessment 480
patient centred outcomes 8–9
patient health status impact 146–7
patient perceptions of 141–2
PEDIS classification 267, 268
plantar pressure elevation 126–8
presentation delays 419
presentations of 481–2
pressure ulcers 119–20
prevalence of 3–5, 17–18
prevention of 10, 57–8, 132–3, 214–15,
378, 414–15
previous foot ulceration 110
psychological factors 139–51
quality of life impact 146–8
re‐admission to hospital 7
recurrence of 5, 6, 133, 204, 378, 411, 435
referral pathway 488–9
risk assessment 93, 111–15
risk factors 6–7, 35, 106–11, 133, 147–8
risk reduction 217–18
in Romania 68
sampling techniques 480–1
self‐care practices 6
severity of ulcer at first assessment 437
sex of patient 109
smart technology 202, 204–11
socio‐economic impact of 146
in Sub‐Saharan Africa 51, 52, 54–5
sufficient cause 116, 117
and trauma 106
treatment of 130–2
types of wound 463
ulcer aetiology 2
in US 441, 459
vascular control 483–4
warning signs 414
wound classification 2–3, 6, 9–10, 235,
236, 238, 243, 268, 291, 434
wound number/location 443
see also diabetic foot infection; wound care/
healing
Diabetic Foot Ulcer Scale (DFS)
questionnaire 147
diabetic neuropathy (DN) 89–103, 110, 170
acute painful neuropathies 94–5
asymmetrical neuropathies 95–7
balance during gait 194–6
bone impact 314
central nervous system involvement in
97–8
chronic neuropathy 108
chronic stable neuropathic foot 164
classification of 89–90
clinical trial assessment 228–9
and depression 140, 144
and DFU pathogenesis 107–9
diagnosis 69, 92, 93, 94
distal symmetrical neuropathy 90,
91–3, 97–8
epidemiology 89
fall risk 193
fracture pattern 163
gait 130, 187–200
Indian Asians, UK 38
management of 98–101

MRI scans 189
muscle atrophy 129, 188
Neuropathy Disability Score 113
Norfolk QoL‐Diabetic Neuropathy
Scale 68
offloading adherence 143–4
pain 91, 94–5
treatment of 98–101
pathogenesis 97–8
peripheral sympathetic autonomic
neuropathy 108–9
prevention of 98
quality of life analysis 68
sensory loss 108, 120
in Sub‐Saharan Africa 52–3
symmetrical neuropathies 91–5
unsteadiness symptom 109, 144–5, 195–6
see also Charcot neuroarthropathy
diabetic truncal radiculopathy (DTR) 90, 96
diabetologists 422
diagnostic codes, ICD‐9 4
dialysis treatment, DFU risk 110
dicloxacillin 270
diffusion tensor imaging (DTI) 181
diffusion weighted imaging (DWI) 179, 180,
181, 182
digital subtraction angiography (DSA)
497, 498
digital technologies
DFU management 215–17
foot monitoring 205
‘digital wellness’ 216
direct digital radiography (DDR) 154, 155
disease models 111, 141
dislocations, Charcot foot 326
see also fractures
distal sensory peripheral neuropathy
(DSPN) 145
distal symmetrical neuropathy 90, 91–3, 94,
97–8
Dixon‐based MR techniques 178–9
DM see diabetes mellitus
DN see diabetic neuropathy
Doppler audible signals, PAD diagnosis 495
Doppler imaging 175
Index 525
dorsal foot temperature 113, 114
dorsalis pedis artery, reconstitution of 240
doxycycline 270, 274
dressings 303–11, 365
compression bandaging 304
cost of 303
definition of 304–5
evidence requirement/quality 304
matrix metalloproteinases
modulation 309
problems 303–4
wound healing 306–8
DSA see digital subtraction angiography
DSPN see distal sensory peripheral
neuropathy
DTI see diffusion tensor imaging
DTR see diabetic truncal radiculopathy
duloxetine 99
Duplex ultrasonography 423, 496–7
DWI see diffusion weighted imaging
dynamic response feet 371
‘dynamic sway’ 195, 196
dynamometers 188–9
e
East Asia 75
Eastern Europe 67–73
economic factors 9–10, 202
education programmes see patient
education
effective mechanical advantage (EMA)
191, 192
Egypt
complementary medicine 80
DFU recurrence 5
diabetic foot disease prevalence 79, 80
elastomer orthosis 367
electrical spinal cord stimulation 100
electrical stimulation, plantar 217–18
electronic diagnostic codes (ICD‐9) 4
electrophysiology 112, 114
elevation test 319
EMA see effective mechanical advantage
embryonic stem cells (ES) 444, 447
emergency patients 425, 489
526 Index
emotional factors
patient distress 147
and self‐care behaviours 141, 142
endothelial progenitor cells (EPCs) 446
endovascular revascularization 238, 250–5,
275, 463
advantages of 252
bypass surgery comparison 253
combined with bypass surgery 252, 254
complications 254
prior to bypass surgery 254
results 253–4
risks of 254
technique 250–2
end‐stage renal disease (ESRD) 330
energy‐storing‐and‐returning feet (ESR) 371
England
costs of diabetic foot disease/treatment
17–29
DFU incidence 17–18
diabetic foot care, guidelines 23
diabetic‐related amputation 105
inpatient beds for diabetic foot
disease 260
National Diabetes Foot Care Audit 25,
303, 435–9
see also Scotland; United Kingdom
enterobacteriaceae 270, 271
entrapment neuropathy 97
EPCs see endothelial progenitor cells
EQ‐5D instrument 19
equinus contractures 336
ertapenem 270
erythema 267
erythrocyte sedimentation rate (ESR)
276, 483
ES see embryonic stem cells
ESF see Estratégia de Saúde da Família
ESR see energy‐storing‐and‐returning feet;
erythrocyte sedimentation rate
ESRD see end‐stage renal disease
Estratégia de Saúde da Família (ESF) 61
Ethiopia
health outcomes for diabetes
population 55
PAD prevalence 54
peripheral neuropathy prevalence 53
ethnicity
and amputation risk 35–8, 36
and DFU risk 110
EURODIAB Prospective Complications
Study 89
Eurodiale Study 1, 2, 7, 20, 62, 146
European Wound Management Association
(EWMA) 226
Europe, diabetes incidence 67
see also Eastern Europe; individual
countries
evidence hierarchy, clinical trial
assessment 226–7
examination of foot see foot examination
exercise
and DFU healing 145
and DFU risk 148
and diabetic neuropathy 196–8
harmful activities 213
levels of 213
management of 211–14
recommendations for diabetes persons
211–14
resistance exercise training 196–7, 198
and smart technology 211–14
weight‐bearing exercise 196, 197
exostectomy 330–1, 337
external moment arm length (ExtMA) 191
f
FAAM see Foot and Ankle Ability
Measurement
FACS see fluorescence‐activated cell sorting
falls, risk of 193
fatalistic attitudes, patients 80
fat‐saturated T2‐weighted (fsT2W)
imaging 178, 179, 181
FBG see Fibre Bragg Grating
FED see Footwear for Every Diabetic
‘Feet at Risk’ clinics 48
femoral neuropathy 95–6
Fibre Bragg Grating (FBG) 205
FIELD Study 33
 Index 527

fifth metatarsal head resection 384, 385 adherence to therapeutic footwear 213,
Fiji 86, 87 215, 406–7
financial costs see costs of diabetic foot and balance impairment 407
disease/treatment bespoke shoes 405, 406
fixation methods, CN midfoot 332–6, 337–8 ‘breaking‐in’ shoes 405–6
flaps choosing for patients with LOPS 405–7
amputation surgery 354, 357, 358, 360, custom‐made footwear 133, 405, 406
361, 362 DFU causation/risk 118, 130
reconstructive surgery 463, 465–8, 469, 470 for diabetic patient with recently healed
Flex Foot 371 ulcer 406
flexor tendon tenotomy 132, 133 for diabetic patient with ulcer 406
flucloxacillin 270 foam cushioning 399
fluorescence‐activated cell sorting footwear pyramid 406
(FACS) 448 in‐shoe plantar pressure 126, 402–3
fluoroquinolone 274, 280 insoles 132, 210, 211, 212–13, 215, 355,
fluroscopy 251 399, 400, 402, 415
foam cushioning, footwear 399 laces 398
focal peripheral neuropathies 96 load transfer 400
folk medicine 80 metatarsal pads and bars 400, 402
Foot and Ankle Ability Measurement need for therapeutic shoes 404
(FAAM) 289–90 offloading
foot care education see patient education by plantar area at risk 403–4
foot clinics see diabetic foot clinics by plantar pressure measurement 401–3
foot compartments 292, 293 orthoses 399–400
foot deformities patient perceptions of 142
Charcot foot 318, 326, 327, 328, 331–3 plantar pressure measurement 401–3, 405
claw toes 92, 119, 128, 413 plantar temperature monitoring 207–10
DFU risk 111 prevention of plantar ulcers 132
effects of 178 remission maintenance 412
hammertoes 413 rigid shoes 400–1
plantar pressure elevation 128 rocker shoes 131, 368, 400, 401
radiography 158 roller shoes 400, 401
‘rocker bottom’ foot 128–9, 330–1 shoe ‘break‐in’ 405–6
foot drop 97 shoe uppers 398
foot examination 112–13, 261–2, 290–1 slip‐on shoes 398
foot infection see diabetic foot infection smart footwear 212–14
foot pressure measurement see plantar smart socks 205, 207–10
pressure measurement smart technology 203–4
foot protection clinics/services 10, 489 temperature and humidity
see also diabetic foot clinics monitoring 210
foot temperature see plantar temperature total contact casts 130, 131, 145, 214, 319,
measurement/monitoring 320, 385–6, 485
foot ulcers see diabetic foot ulcer velcro closure 398
footwear 81, 92, 130–3, 336, 397–410, 482, versus surgery 404
484–5 see also gait
528 Index
Footwear for Every Diabetic (FED) 48
footwear technicians 48
forefoot osteomyelitis, surgery 388–90
foreign bodies, radiography 174
fractures
Lisfranc fracture 163, 171
radiography 156, 157, 158–60
see also dislocations
free flaps, reconstructive surgery 466–8, 469
Fremantle Diabetes Study 33
fsT2W (fat‐saturated T2‐weighted)
imaging 178, 179, 181
g granulocyte colony stimulating factor
gabapentin 99, 100
gadolinium contrast, MRI scans 179, 498
gait 144, 145, 187–200
ankle joint during walking 191–2
and balance 194–6
biomechanics of 188–92
characteristics of diabetes persons 187–8
diabetic neuropathy 130
exercise effects 197–8
fall risk 193
‘hip strategy’ 192
improvement strategies 190–2
measurement of 204–5
metabolic cost of amputation 348–9
metabolic cost of walking 192
muscle forces 188–90
stair‐walking 195
step width 195–6
unsteadiness during walking 195–6
walking speed 191, 192, 348
wearable technologies 203–4
weight‐bearing function of foot 348
see also footwear
gangrene 55, 56, 68, 157
gases, topical, wound healing 308
gas, in soft tissues 162, 291, 294
gastrocnemius recession 299, 336, 386
G‐CSF see granulocyte colony stimulating
factor
GDP see gross domestic product
gene expression analyses 448–9, 450
genetic factors, Charcot foot 317–18
geriatric depression, and DFU healing
142–3
Global Lower Extremity Amputation
Study 34
glycaemic control 33, 94–5, 98, 99, 329–30,
379, 483
glycated haemoglobin (HbA1C) 483
glycosylation 129
Google 217
gout 164–5
graft tunnelling, bypass surgery 242
Gram stains 56
(G‐CSF) 266
GRF see ground reaction force
Grodinsky, Manuel 292
gross domestic product (GDP), diabetes cost
comparison 202
ground reaction force (GRF) 191, 371
growth factors, wound healing 444, 450
h
haemodialysis, EQ‐5D score 19
haemostasis 295, 353
half shoes 131
hallux (great toe) amputation 354–5, 367,
379, 380
hallux (great toe) surgical
reconstruction 379–82
hallux valgus (bunion) 92, 111, 334, 355,
356
hammertoes 413
hASCs see human adipose‐derived stems
cells
HbA1C see glycated haemoglobin
healer’s medicine 80
healing see wound healing
healthcare costs see costs of diabetic foot
disease/treatment
healthcare priorities, setting of 22–5
health outcomes
and access to healthcare 25
clinical audit of foot care 432–4, 437, 438
clinical trial assessment 230–1

and delayed presentations 52
diabetic foot ulcer 7–8
Sub‐Saharan Africa, diabetes
populations 55
health‐related quality of life (HRQoL) 8, 19
health status of patients, DFU impact on
146–7
heel ulcers 182, 386, 403
hematopoietic stem cells (HSCs) 447
hemorrhagic callus, self‐examination for 414
henna paste 80
herbal medicine 80
HIF‐1 see hypoxia‐inducible factor 1
hindfoot
amputation 357, 359
realignment arthrodesis 334
‘hip strategy’, gait 192
Hispanic Americans, diabetes‐related
amputation risk 37
histology, bone specimen analysis 316–17
honey‐impregnated dressings 308
hospitalization
for diabetic foot infection 508
for diabetic foot ulcer 4, 5, 7
inpatient care 259–64, 427
pressure ulcer prevention 262
hot foot baths 81
hot swollen foot, diagnosis and treatment
475–8
hot‐water bottles 81
HRQoL see health‐related quality of life
HSCs see hematopoietic stem cells
human adipose‐derived stems cells
(hASCs) 445, 449, 450
humidity data, insoles/soles of footwear 210
Hungary 70
hydrogel dressings 307
hydrotherapy 307
hyperbaric oxygen therapy 275
hyperglycemia 98, 266, 329, 444, 460
hypoxia‐inducible factor 1 (HIF‐1) 444
i smart insoles 212–13, 215, 415
ICD‐9 diagnostic codes 4
IDF‐WPR Diabetic Foot Care Project 75, 76
Index 529
IDSA see Infectious Diseases Society of
America
imaging
DFU diagnosis 481, 482–3
future directions 181–3
modalities 170–3
peripheral arterial disease 496–8
see also computed tomography; magnetic
resonance imaging; nuclear imaging;
positron emission tomography;
radiography; ultrasound
imipenem‐cilastatin 271
imipramine 99
incisions, surgical 292–4, 295, 358, 381
India 43–5, 57
Indian Asians, UK
DFU risk 35
diabetes‐related amputation risk 35, 38
diabetic neuropathy rates 38
PAD rates 38
indirect load transfer, amputation 352
induced pluripotent stem (iPS) cells 442
infection, foot see diabetic foot infection
infection tracking, surgery 294
infectious disease consultation 296
Infectious Diseases Society of America
(IDSA)
antibiotic treatment 270–1
DFI classification 267, 507
inpatient care 259–64, 427
costs of diabetic foot disease/treatment
21, 260–1
foot examination on admission 261–2
multidisciplinary foot services 261, 262
pressure ulcer prevention 262
insensate foot, physical activity
recommendations 211–14
see also loss of protective sensation
insoles
metatarsal pads and bars 132, 400, 402
orthotic 355, 399
shear‐reducing insoles 211
temperature and humidity
monitoring 210
530 Index
instability see balance, impairment
Integra (skin substitute) 464
integrated care framework 488–9
internal Achilles tendon moment arm 191
internal moment arm length (IntMA) 191
International Working Group of the
Diabetic Foot (IWGDF) 225,
226, 266, 273
Internet of Things (IoT) 216–17
interphalangeal joint (IPJ)
neuropathic ulcer under 381
surgical reconstruction 379–80, 381,
386, 388
interventional radiologists 423
IntMA see internal moment arm length
intra‐arterial digital subtraction
angiography 498
Ionizing Radiation (Medical Exposures)
Regulations (IR(ME)R) 153
IoT see Internet of Things
IPJ see interphalangeal joint
iPS see induced pluripotent stem cells
Ipswich Touch Test (ITT) 114
Iraq, diabetic foot disease prevalence
79, 80
IR(ME)R see Ionizing Radiation (Medical
Exposures) Regulations
irremovable total contact casts (iTCCs) 214
irrigation, surgical 295
ischemia
BASIL trial 253, 254
chronic limb‐threatening ischemia 235,
237, 238
ischemic diabetic foot 470, 481
neovascularization response 445–6, 447
neuroischemic ulcers 419, 463, 482
and surgery outcomes 379
iTCCs see irremovable total contact casts
ITT see Ipswich Touch Test
Ivory Coast
health outcomes for diabetes
population 55
PAD prevalence 54
IWGDF see International Working Group of
the Diabetic Foot
j
joint specialist clinics 425–6, 427
joint torque profiles 190
Jones fracture of the fifth metatarsal 159
Jordan
DFU in 80
diabetic foot disease prevalence 79
J wire 250, 251
k
Keller arthroplasty 380, 382
Kenya
health outcomes for diabetes
population 55
PAD prevalence 54
peripheral neuropathy prevalence 53
keystone design perforator island flaps 465
keystone flaps 465
kidney disease/impairment 18, 44, 110, 254,
330
K levels (Medicare Functional Classification
Measure) 365–6
knee abscess 171
knee disarticulation amputation 350,
351, 361
prosthetics 371–2
knee‐high walkers 130, 131
knee units 373
Kuwait, diabetic foot disease prevalence
79, 80
Kyoto Foot Meeting Project 75
l
Laboratory Risk Indicator for Necrotising
Fasciitis (LRINEC score) 291
laboratory tests 276, 291, 420, 483
laces, footwear 398
large fibre function assessment 92
larval debridement 275, 280, 307, 483
‘last resort’ referral model 204
lateral supramalleolar flaps 465–6
LDA see Linear Discrimination Analysis
leadership, diabetic foot clinics 428
lead zirconate titanate (PZT) piezoceramic
sensors 205

LEA (lower extremity amputation) see
amputation
LEAP see Lower Extremity Assessment
Project
Lebanon 80
leg bypass operations see bypass surgery
lesser metatarsal heads, surgery 383–5
lesser toes
amputation 355, 356
surgical reconstruction 382–3
leucocyte scans 277
leukocytosis 291
levofloxacin 270, 271
LHBs see Local Health Boards
lifestyle, health implications of 81
lignocaine, intravenous 100
limb preservation, relative benefit of 241
Linear Discrimination Analysis (LDA) 449
linezolid 271, 274
Lisfranc fracture dislocation 163, 171
load transfer, footwear 400
local flaps, reconstructive surgery
465–6, 468
Local Health Boards (LHBs) 436
locking plate fixation, CN midfoot 332
Loeffler‐Ballard incision 292
loss of protective sensation (LOPS)
diagnosis 397
footwear for patients with 398, 399,
405–7
see also insensate foot
lower extremity amputation (LEA) see
amputation
Lower Extremity Assessment Project (LEAP)
347, 350
Lower Extremity Threatened Limb
Classification System 235, 236,
238, 243
LRINEC score (Laboratory Risk Indicator for
Necrotising Fasciitis) 291
m Amputation Limb Salvage Study
MAC see medial artery calcinosis
maggots (larvae), wound cleaning 275, 280,
307, 483
Index 531
magnetic resonance imaging (MRI) 167,
170–2, 177–81, 483
apparent diffusion coefficient 179–81, 182
Charcot foot 174, 177, 178, 179
contrast enhancement 179, 498
diffusion weighted imaging 179, 180,
181, 182
Dixon‐based techniques 178–9
gadolinium contrast 179, 498
intramuscular non‐contractile
material 189
multiplanar imaging 179
muscle atrophy, diabetic neuropathy 129
osteomyelitis diagnosis 176, 181, 277
procedure 178
short TI inversion recovery sequence 178
Malta 5
Maori people 86
Marshall Islands 87
matrix metalloproteinases (MMPs) 143, 309
MD‐CTA see multidetector‐row computed
tomography angiography
MDFCTs see Multidisciplinary Diabetic Foot
Care Teams
MDFS see multidisciplinary foot services
MDROs see multidrug‐resistant organisms
ME see Middle East
medial artery calcinosis (MAC) 296, 329
medial plantar flaps 465–6
median nerve palsy 97
medical costs see costs of diabetic foot
disease/treatment
Medicare Functional Classification Measure
(MFCM) 365–6
Medicare patients 37
Meggitt‐Wagner wound classification 2, 3,
6, 434
mesenchymal stem cells (MSCs) 442, 444,
447, 449, 451
meta‐analyses 227
METALS see Military Extremity Trauma/
metatarsal head procedures 379–82
metatarsal head resection (MHR) 129, 379,
384–5, 386, 388
532 Index
metatarsal heads (MTHs), offloading
footwear 402
metatarsal (MT) pads and bars 400, 402
metatarsal osteotomy 383–4
metatarsophalangeal joint (MPJ), surgical
reconstruction 379–82, 386
methicillin‐resistant S. aureus (MRSA)
269–74, 509
treatment of 273–4
Mexican Americans, diabetes‐related
amputation risk 37
MFCM see Medicare Functional
Classification Measure
mHealth (mobile health) 215–16
MHR see metatarsal head resection
microangiopathy 181
microbiological control, diabetic foot
ulceration 485–7
microbiologists 423–4
microbiology, diabetic foot infection
268–72, 481
Micronesia 87
microprocessor knees 373
microsurgery, reconstructive 466–8
microvascular complications, DFU risk 110
Middle East (ME) 79–83
midfoot
amputation 357, 358
Charcot foot deformity correction 327,
328, 331–3, 335
cross‐sectional view 293
osteomyelitis, surgery 390
midfoot ulcers 403
Military Extremity Trauma/Amputation
Limb Salvage Study (METALS) 348
minimal invasive surgery (MIS) 383
minor amputation 17, 24, 32, 146
MIS see minimal invasive surgery
MMPs see matrix metalloproteinases
mobile health (mHealth) 215–16
mobile phones 215
see also smartphones
moisturizing creams 81
monocytes 265, 266, 316
monofilament testing 92
mononeuropathy (mononeuritis complex) 90
morphine 100
mortality
amputation 7–8, 20, 31, 201, 239, 459
bypass surgery 237
diabetic foot ulcer 7–8, 20, 479
risk for diabetic patients 6–8, 20
Sub‐Saharan African diabetic patients 56
‘Morton’s extension’ 355
motor neuropathy 110, 129
moxifloxacin 270
MPJ see metatarsophalangeal joint
MRI see magnetic resonance imaging
MRSA see methicillin‐resistant S. aureus
MSCs see mesenchymal stem cells
MT see metatarsal pads and bars
MTHs see metatarsal heads
multidetector‐row computed tomography
angiography (MD‐CTA) 497
multidisciplinary approach, reconstructive
surgery 460, 461
Multidisciplinary Diabetic Foot Care Teams
(MDFCTs) 47–8, 49
multidisciplinary foot services (MDFS) 261,
262, 488
multidisciplinary teams, diabetic foot
clinics 425–6
multidisciplinary treatment, diabetic foot
ulcer 10
multidisciplinary vascular radiology
meetings 426–7
multidrug‐resistant organisms
(MDROs) 269
muscle denervation, neuropathic 178
muscle forces, and gait 188–90
muscle strength
improvement in 197–8
tests 188–9
muscular weakness and wasting 92, 96, 110,
129, 188
musculoskeletal examination 290–1
n
NaDIA see National Diabetes Inpatient Audit
nails see toenails
 Index 533

National Diabetes Audit (NDA) 435 neuropathic ulcers 463

National Diabetes Foot Care Audit of neuropathy see diabetic neuropathy
England and Wales (NDFA) 25, 303, Neuropathy Disability Score (NDS) 113
425, 435–9 Neuropathy and Foot‐Ulcer‐Specific Quality
clinical outcomes 437, 438 of Life instrument (NeuroQoL) 147
dataset limitations 438 neuropeptides 315
design of 436–7 New Zealand (NZ)
findings of (2014‐17) 437–9 amputation rates 86
foot care pathway 436 DFU prevalence 87
structural audit 438 South Asian diabetes‐related
variation between service providers 438 amputation 38
National Diabetes Inpatient Audit NICE see National Institute for Health and
(NaDIA) 260, 261, 262 Care Excellence
National Health Service (NHS), clinical audit Nigeria
of foot care 435 health outcomes for diabetes
National Inpatient Sample (NIS), US 4 population 55
National Institute for Health and Care PAD prevalence 54
Excellence (NICE) peripheral neuropathy prevalence 53
diabetic foot care framework 23 NIS see National Inpatient Sample
EQ‐5D instrument 19 non‐healing ulcers 449
inpatient care guidelines 261 see also reconstructive surgery
Native Americans, diabetes‐related non‐invasive bedside testing, PAD
amputation risk 35–7 diagnosis 494
navicular fracture 158, 159 Norfolk QoL‐Diabetic Neuropathy Scale 68
NDA see National Diabetes Audit Norway, clinical audit of foot care 439
NDFA see National Diabetes Foot Care Audit Novartis 217
of England and Wales NPWT see negative pressure wound therapy
necrosis 419, 442, 469 NSF see nephrogenic systemic fibrosis
necrotising fasciitis 162, 291 nuclear imaging, osteomyelitis
negative pressure wound therapy diagnosis 277
(NPWT) 297, 308–9, 483 nurses 422
neovascularization 445–7, 449 nutrition 460
nephrogenic systemic fibrosis (NSF) 498 NZ see New Zealand
nephrotoxicity 254
nerve entrapment 97 o
nerve transection 354 occupational therapists 424
NeuRODiab see Society for Diabetic oedema
Neuropathy DFU risk 110
neuroischaema 483 fsT2W imaging 178
neuroischemic ulcers 53, 419, 463, 482 MRI scans 174, 180, 182
neurological assessment 113–14, 290 radiographs 172
neuropathic pain 91, 98–101 treatment 487
not responding to pharmacological offloading 130–2, 133, 298
treatment 100 adherence to 143–4, 145, 148, 214–15
treatment algorithm 100, 101 Charcot foot 319–20
534 Index
offloading (cont’d)
smart technology 203–4
surgical offloading 378–9, 385–6, 413
therapeutic footwear/orthoses 401–4, 412
OPAT see outpatient parenteral antibiotic
therapy
open bypass surgery see bypass surgery
opiates, neuropathic pain management 100
orthopaedic clinics 426
orthopaedic surgeons 423, 426
orthotics 367–8, 399–400, 405
ankle foot orthosis 357
design optimization 403
in‐shoe plantar pressure 403
insoles 355, 399
orthotists 422
osseous structures, surgical reconstruction
298–9
ossicle, accessory 166
osteoarthropathy 178
osteoclast activation, Charcot foot 316
osteoclastogenesis 330
osteolysis 317
osteomyelitis 170, 275–81, 482, 483
amputation 388
antibiotic versus surgical treatment 512
characteristics of 277
CT scans 176
diagnosis 276–8
bone biopsy 278
clinical findings 276
imaging studies 276–8
laboratory tests 276
probe‐to‐bone test 276
strategies 278, 279
forefoot osteomyelitis, surgery 388–90
incidence of 275
infection identification 480
management of 279
midfoot osteomyelitis, surgery 390
MRI scans 167, 176, 181
positron emission tomography 278
radiographs 155, 157, 160–2, 174, 276–7
rear foot osteomyelitis, surgery 390–1
serial radiography 156
treatment 275–6, 278–81, 509, 512
adjunctive therapy 280
antibiotic treatment 278, 280–1
challenges of 278
duration of 280–1
surgery 280, 377, 387–91
osteopenia 163
osteoprotegerin (OPG) 316, 318
osteotomy, metatarsal 383–4
outcomes see health outcomes
outpatient care, costs of diabetic foot care,
England 21
outpatient parenteral antibiotic therapy
(OPAT) 427
over‐the‐counter medicines 80
oximetry tests 237, 496
oxycodone 100
oxygen tests, transcutaneous 248
oxygen, topical, wound healing 308
p
Pacific region 75–7, 86–7
PACS see picture archive and communication
system
PAD see peripheral arterial disease
pain
abdominal pain 96
loss of 120
neuropathic pain 91, 94–5, 98–101
purpose of 108
pain clinics 100
‘painful–painless leg’ 108
Pakistan 47–9
Pakistan Working Group on the Diabetic Foot
(PWGDF) 48
palliative wound care 239
palsies 96, 97
pan metatarsal head resection 385, 386
Papua New Guinea 86, 87
patellar tendon bearing sockets 369
patient centred outcomes 8–9
patient education
Brazil 64
Cochrane review 487
efficacy of 139–40
 Index 535

in India 57 Indian Asians, UK 38

remission maintenance 413–14 intra‐arterial digital subtraction
Romania 68–9 angiography 498
Saudi Arabia 81–2 management of 250
smart technology 214–15 multidetector‐row computed tomography
Sub‐Saharan Africa 56–8 angiography 497
patient health status, DFU impact on 146–7 non‐invasive bedside testing 494
Patient Interpretation of Neuropathy (PIN) in Pakistan 47–8
questionnaire 142 pathophysiology of 248
patient perceptions pulse oximetry 496
of balance impairment/unsteadiness skin perfusion pressure 496
144–5, 148 in Sub‐Saharan Africa 51, 53–4
of DFU risk 141–2 testing for 481–2
PCR see polymerase chain reaction toe brachial index 495
pedal access technique, endovascular toe pressure measurement 495
revascularization 251 transcutaneous oxygen tension
pedal fracture, athletes 158 measurement 495–6
PEDIS classification 267, 268, 434, 507 ultrasound scans 175
PEDIS Grade 2 (mild) infections 273–4 vascular evaluation 494–6
PEDIS Grade 3 (moderate) infections 274 algorithms 498, 499, 500
PEDIS Grade 4 (severe) infections 274–5 vascular imaging 496–8
peer counselling 354 in Western Pacific region 76
pencillin 273 peripherally inserted central catheters
perforator flaps 465, 467–8, 469, 470 (PICCs) 427
peripheral arterial disease (PAD) 6, 247–57, peripheral neuropathy (PN) see diabetic
493–504 neuropathy
amputation risk factor 33 peripheral sympathetic autonomic
ankle brachial index 494–5 neuropathy 108–9
ankle Doppler signals 495 peripheral vascular disease (PVD)
assessment for 329 bypass surgery 235–45
bypass surgery 235–45 in India 44
clinical examination 494 radiography 157
clinical significance of 434 Peru, DFU and amputation prevention 10
clinical trial assessment 228 PET see positron emission tomography
colour Doppler ultrasound 496–7 phalanges, bone resorption 164
contrast‐enhanced magnetic resonance phantom‐limb pain 353–4
angiography 498 pharmacists 424
definition of 434, 493 phlebotomy service 422
and DFU pathogenesis 106–7 photographs, clinical 166
diagnosis 248–9, 494–6 physical activity
endovascular revascularization 250–5 and DFU risk 148
history 494 and diabetic neuropathy 196–8
identification of 235–7 harmful activities 213
imaging 496–8 and healing 145, 214
incidence of 106, 247–8 levels of 213
536 Index
physical activity (cont’d)
management of 211–14
recommendations for diabetes persons
211–14
and smart technology 211–14
weight‐bearing exercise 196, 197
physiological stress, and DFU healing 143
physiotherapists 424
physiotherapy 96
PICC lines 427
picture archive and communication system
(PACS) 166
piezoceramic sensors 205
PIN see Patient Interpretation of Neuropathy
pinprick test 113
pin suspension 370
piperacillin‐tazobactam 271, 274
placental membrane, wound closure 297
plain radiography see radiography
plantar area at risk, offloading 403–4
plantar electrical stimulation 217–18
plantar foot, compartments of 292, 293
plantar plating, Charcot foot 332
plantar pressure, and diabetic foot ulcer
119–20
plantar pressure elevation
measurement of 126, 127–8, 132
mechanisms of 128–30
peak pressure threshold 133
plantar pressure measurement 113, 114,
115, 125–8, 132, 204–8, 212–13, 401–3
concept of pressure 125–6
orthoses 405
peak pressure threshold 127
plantar temperature measurement/
monitoring 204, 206–10, 211,
319, 415
plastic clinics 427
plastic surgeons 423
see also reconstructive surgery
plastic surgery consultation 296
platelet‐rich plasma (PRP) 450
plexopathy 95–6
PMN see polymorphonuclear cells
pneumatic knee units 373
PN (peripheral neuropathy) see diabetic
neuropathy
podiatrists 421–2
podiatry 69, 488
Podimetrics mat 207
polymerase chain reaction (PCR) 448
polymorphonuclear cells (PMN) 265, 266
polytetrafluoroethylene (PTFE) prosthetic
conduit 242
popliteal artery revascularization 253
populations
clinical audit of foot care 434
clinical trials 227–8
porcine products, wound healing 464
positron emission tomography (PET)
153–4, 278
postural instability see balance, impairment
prealbumin 460
pregabalin 99
preoperative care 378–9
prescription shoes see footwear
presentation delays 419
pressure assessment/perception see foot
pressure assessment/perception
pressuremat 112
pressure palsies 97
PressureStat Foot Print 114, 115
pressure ulcers, prevention of 262
prevention programmes see patient education
primary care, costs of diabetic foot care,
England 21
probe‐to‐bone test, osteomyelitis
diagnosis 276
progenitor cells 444–5, 446, 447
propeller flaps 465, 466, 469
prophylactic surgery 377–86
prostate cancer 18, 19
prosthetics 365–76
ankle‐foot components 371–3
foot amputation 366–8
foot orthotics 367–8
K levels 365–6
knee disarticulation amputation 371–2
knee units 373
lower limb amputation 365–6
 Index 537

Medicare Functional Classification measurement of 147–8

Measure 365–6 patient‐reported outcome measures 8
metabolic cost of walking with a prosthesis quantitative sensory testing (QST) 114
348–9 questionnaires
shanks 370 Diabetic Foot Ulcer Scale 147
sockets 350–2, 369, 372–3 foot care pathway 436
suspension 370, 372–3 Patient Interpretation of Neuropathy 142
transfemoral amputation 372
transtibial amputation 368–70 r
transtibial sockets 369 race see ethnicity
proximal foot amputation, prosthetics 368 radial nerve palsy 97
proximal motor neuropathy 95–6 radiculopathy, truncal 90, 96
PRP see platelet‐rich plasma radio frequency energy, wound healing
Pseudomonas aeruginosa 269, 271, 509 efficacy 218
psychiatrists 424 radiography 153–68, 170, 173–4, 481,
psychological factors 139–51 482–3
DFU development 139–42 Charcot foot 156, 162–4, 172, 173, 174,
DFU healing 142–5 319, 326, 327–8, 333
quality of life impacts 146–8 clinical information 166
PTFE see polytetrafluoroethylene prosthetic computerized radiography 154, 155
conduit DFI evaluation 291
publications, DFU‐related 225, 226 direct digital radiography 154, 155
pulsed radio frequency energy, wound foot deformities 158
healing efficacy 218 foreign body identification 174
pulse oximetry 496 fractures 158–60
‘Putting Feet First’ campaign 261 gas, in soft tissues 294
PVD see peripheral vascular disease gout 164–5
PWGDF see Pakistan Working Group on the image resolution 154–5
Diabetic Foot justification for 153
pyomyositis, ultrasound scans 175 limitations of 154
PZT see lead zirconate titanate piezoceramic Lisfranc dislocation 171
sensors normal variants 165–6
osteomyelitis 155, 157, 160–2, 174, 276–7
q patient preparation 156
QALYs see quality‐adjusted life years peripheral vascular disease 157
QoL see quality of life photographic correlation 166
QST see quantitative sensory testing projections 156
quality‐adjusted life years (QALYs) radiation risk 153
19, 23–4 serial radiography 156–7
quality of care 23 traumatic ulcer 117
quality of life (QoL) 19 ulceration predictors 327–8
amputation impact 347, 348 vasculopathy 157
DFI impact on 289 radiologists 423
DFU impact on 146–8 randomized controlled trials (RCTs)
diabetic neuropathy patients 68 226–7, 304
538 Index
RANKL see receptor activator of nuclear
factor kappa‐B ligand
ray resection 355–7, 367
RCTs see randomized controlled trials
RCWs see removable cast walkers
realignment arthrodesis 331–4, 333, 337
rear foot osteomyelitis, surgery 390–1
receptor activator of nuclear factor kappa‐B
ligand (RANKL) 316, 317, 318, 320
reconstructive surgery 459–73
and amputation 468
care spectrum 460, 461
debridement 462–3
elevator approach 461–2, 466
flap reconstruction 463, 465–8
failures 468
flap survival rate 468
free flaps 466–8, 469
goals of 467
local flaps 465–6, 468
indications for surgery 466–7
microsurgery 466–8
multidisciplinary approach 460, 461
reconstruction algorithms 461–2
skin grafts/substitutes 464–5
step‐ladder approach 461, 466
supermicrosurgery 468, 469
survival rate 468
vascular status evaluation/
enhancement 463–4
wound‐closure ladder 461
recurrence of DFU 5, 6, 133, 204, 378,
411, 435
referral pathway 488–9
regenerative medicine 441–57
advances in 449–51
stem cells 441–4, 446–51
functional heterogeneity of 448–9
vascular dysfunction 445–7
wound healing 444–5
region perspectives see country/region
perspectives
Regulations, Ionizing Radiation (Medical
Exposures) 153
religious practices 81
remission 411–17
components of 412
footwear 412
monitoring technology 415
offloading footwear 412
patient education 413–14
self‐care behaviours/practices 414
surgical offloading 413
wearable technology 415
removable cast walkers (RCWs) 131, 145, 214
renal disease/impairment 18, 44, 110,
254, 330
resistance exercise training 196–7, 198
revascularization see bypass surgery;
endovascular revascularization
reverse sural flaps 465–6
rheumatoid arthritis 126
risk assessment
amputation 32–3
bypass surgery 237–9
DFU risk 111–15, 204–11
of diabetic foot 93
screening techniques for ‘at‐risk’ foot 112
‘rocker bottom’ foot 128–9, 330–1
rocker shoes 131, 368, 400, 401
roller shoes 400, 401
Romania 67–9
Rothman model, DFU causation 116
Russian Federation 9, 70–1
Rydel Seiffer tuning fork 44
s
SA see Saudi Arabia
S(AD)SAD wound classification 2, 3, 6
Samoa 87
sampling techniques 269, 295, 480–1
San Antonio wound classification 9–10
Sanders and Frykberg Anatomic
Classification for Charcot
Osteoarthropathy 327
Saudi Arabia (SA) 79, 80
Saving the Diabetic Foot Project 61, 62
SbS see Step by Step foot projects
SCIP see superficial circumflex iliac artery
flap

Scotland
DFU incidence 18
Diabetes Audit and Research in Tayside
Scotland study 106
Seattle Diabetic Foot Study 2
sedentary lifestyle 81
Seldinger technique, endovascular
revascularization 250, 251
selective serotonin and norepinephrine
reuptake inhibitors (SSNRIs)
99–100, 101
self‐care behaviours/practices
amputation risk 6
and depression 140–1
DFU risk 6, 141–2
poor self‐care 147–8
remission maintenance 414
Sensoria Socks 205
sensorimotor neuropathy, and DFU
pathogenesis 108
sensor technologies 217
sensory loss, diabetic neuropathy 91, 95,
108, 109, 120
SENSUS (wearable electrical stimulation
system) 217, 218
sepsis 55, 267
serial radiography 156–7
serotonin and norepinephrine reuptake
inhibitors (SNRIs) 99–100, 101
sesamoid bones, radiography 156, 165
sesamoidectomy 382, 386
sex of patient, and DFU risk 109
SF‐36 physical functioning scale
146, 147
SFA see superficial femoral artery
shanks, prosthetics 370
sharp debridement 306–7
shear stress
plantar foot ulcer 128
thermal stress response assessment
210–11
shoelaces, tightness of 211
shoes see footwear
Shore A scale 399
Short Form (36) Health Survey 146, 147
Index 539
short TI inversion recovery (STIR)
sequence 178
Silfverskiold test 299
SINBAD classification system
434, 437, 482
Single‐Axis Foot 371
single‐cell transcriptional analysis 448
single photon emission computed
tomography (SPECT) 172–3
Siren Socks 209–10
SIRS see systemic inflammatory response
syndrome
Sistema Único de Saúde (SUS) 61
Site, Ischaemia, Neuropathy, Bacterial
Infection, Area and Depth (SINBAD)
classification 434, 437, 482
Size (Area, Depth), Sepsis, Arteriopathy,
Denervation (S(AD)SAD) wound
classification 2, 3, 6
skin examination, DFI evaluation 290
skin grafts/substitutes 308, 464–5
skin perfusion pressure (SPP) 237, 496
skin temperature measurement see plantar
temperature measurement/
monitoring
sleeve suspension 370
slip‐on shoes 398
Slovak Republic 70
SM see surface marker profiles
smartphones 205, 212
SmartSox 207–9, 208, 415
smart technology 201–24
DFU prevention 214–15
DFU risk assessment 204–11
footwear‐related offloading treatment
203–4
Internet of Things 216–17
offloading treatment 203–4
patient education 214–15
physical activity management 211–14
remission maintenance 415
therapy in the home 217–18
wearable technology 203–4, 216–18, 415
smartwatches 205, 212–13
smoking 33, 143, 487
540 Index
SNRIs see serotonin and norepinephrine
reuptake inhibitors
Society for Diabetic Neuropathy
(NeuRODiab) 69
socio‐economic factors 34, 146
sockets, prosthetics 369, 372–3
socks, smart technology 205, 207–10
soft tissue envelope, amputation surgery
350, 352, 353, 357
soft tissues, gas in 291, 294
soft tissue/tendon balancing 299
soft tissue ulceration 162
solid ankle cushioned heel (SACH) 371
Solomon Islands 87
Somerset Clinical Commissioning Group,
foot care service 24
South Africa
PAD prevalence 54
peripheral neuropathy prevalence 53
South Asians, UK see Indian Asians, UK
SPECT see single photon emission computed
tomography
split thickness skin grafting (STSG) 297–8
SPP see skin perfusion pressure
SSA see Sub‐Saharan Africa
SSNRIs see selective serotonin and
norepinephrine reuptake inhibitors
stair‐walking, and balance/fall risk 193,
195, 407
standing, and DFU risk 213
Staphylococcus aureus 269, 270, 276, 509
stem cells 441–51
adipose‐derived stems cells 441, 443, 444,
449–50
bone marrow‐derived stem cells 451
embryonic stem cells 444
functional heterogeneity of 448–9
hematopoietic stem cells 447
human adipose‐derived stems cells 445,
449, 450
mesenchymal stem cells 442, 444, 447,
449, 451
stents 253
Step by Step (SbS) foot projects 48, 57, 62, 64
STIR see short TI inversion recovery sequence
stress, and DFU healing 143
stroke 18, 20
stromal vascular fraction (SVF) 444
STSG see split thickness skin grafting
subcutaneous tunnelling, bypass
surgery 242
Sub‐Saharan Africa (SSA) 51–60
DFI in 55–6
DFU in 51, 52, 54–5
diabetes incidence and prevalence 51
education programmes 56–8
health outcomes for diabetes
populations 55
mortality rates in diabetic patients 56
PAD in 53–4
peripheral neuropathy in 52–3
prevention programmes 56–8
suction sockets 369
suction suspension 370
Sudan
health outcomes for diabetes
population 55
PAD prevalence 54
peripheral neuropathy prevalence 53
superconstruct fixation 332, 335
superficial circumflex iliac artery (SCIP)
flap 470
superficial femoral artery (SFA) 251, 253
supermicrosurgery 468, 469
supracondylar/suprapatellar sockets 369
surface marker (SM) profiles 447
surgery 289–302, 377–95, 459–73
Achilles tendon lengthening 129, 299,
336, 337, 357, 385–6, 404, 413
classification of 377
clinical trial assessment 231
deformity correction 413
DFU prevention 378
diabetic foot infection 289–302
fifth metatarsal head resection 384, 385
first metatarsal head procedures 379–82
hallux (great toe) procedures 379–82
incision techniques 292–4, 381
interphalangeal joint reconstruction
379–80, 386, 388

lesser metatarsal heads 383–5
lesser toes 382–3
metatarsal head procedures 379–85
metatarsal head resection 384–5, 386, 388
metatarsal osteotomy 383–4
metatarsophalangeal joint
reconstruction 386
microsurgery, reconstructive 466–8
minimal invasive surgery 383
osteomyelitis treatment 280, 377, 387–91
conservative approach 387–8
forefoot osteomyelitis 388–90
midfoot osteomyelitis 390
rear foot osteomyelitis 390–1
pan metatarsal head resection 385, 386
plantar foot ulcers 132, 133
post‐operative evaluation 176–7
preoperative care 378–9
prophylactic surgery 377–86
reconstructive surgery 459–73
supermicrosurgery 468, 469
surgical offloading 378–9, 385–6, 413
toe reconstruction 382–3
vascular surgery consultation/
evaluation 460
versus footwear modification 404
see also amputation; bypass surgery;
Charcot neuroarthropathy (Charcot
foot), surgical reconstruction
SurroSense Rx 212–13, 415
SUS see Sistema Único de Saúde
suspension, prosthetics 370, 372–3
SVF see stromal vascular fraction
swab specimens 269
sweat indicator test 114
swollen foot, diagnosis and treatment
475–8
Syme’s ankle disarticulation amputation
357, 358–9, 360
symmetrical neuropathies
acute painful neuropathies 94–5
distal symmetrical neuropathy 91–3
systematic reviews 227, 273
systemic inflammatory response syndrome
(SIRS) 267, 291
Index 541
t
T1 weighted imaging 178, 179
TAL see tendon Achilles lengthening
talectomy 334
talus, tibiotalocalcaneal arthrodesis 334
Tanzania
DFU in 54–5
health outcomes for diabetes
population 55
PAD prevalence 54
peripheral neuropathy prevalence 53
Step by Step foot projects 57
TASC see TransAtlantic Inter‐Society
Consensus II guidelines
TBI see toe brachial index
TCA see tricyclic antidepressants
TCCs see total contact casts
TcPO2 see transcutaneous oxygen tension
measurement
Technetium Sulphur colloid imaging 177
technology see smart technology
temperature perception, dorsal foot
113, 114
tendinopathy, ultrasound scans 175
tendon Achilles lengthening (TAL) 129,
299, 336, 337, 357, 385–6, 404, 413
tenosynovitis 175, 181
tenotomy 132, 133, 389
TENS see transcutaneous electrical nerve
stimulation
‘terminal Syme’s amputation’ 354
Texas University wound classification 2, 3,
6, 291, 434
textile pressure sensors 205
TG see triglyceride
Thailand 10, 75
therapeutic footwear see footwear
therapies, clinical trials, assessment
of 225–34
thermal stress response (TSR) 210–11
thermography tools 206–7
thermometry 319, 415
tibial disease 252
tibial revascularization 253–4
tibiotalocalcaneal arthrodesis 334
542 Index

tigecycline 271 Translating Research Into Action for Diabetes

time trends data, amputation 34–5 (TRIAD) 4
Timor‐Leste 87 transmetatarsal amputation (TMA),
Tip therm 44 orthotics 367–8
tissue management, amputation 353–4 transplantation patients, DFU risk 111
tissue regeneration 446, 447 transtibial amputation 299–300, 337, 352,
tissue sampling 269, 295, 480–1 359–61
tissue viability, colour guide 294 prosthetics 368–70
TMA see transmetatarsal amputation transtibial sockets 369
TNF see tumor necrosis factor trapped nerves 97
toe brachial index (TBI) 329, 495 trauma
toe filler 355, 357, 367 and DFU 106, 117, 127
toenails inflammatory response in Charcot foot
fungal infection of 55 315–16
trimming of 81 nail trimming 81
toe pressure treatment costs see costs of diabetic foot
PAD diagnosis 248, 495 disease/treatment
tests 237 TRIAD see Translating Research Into Action
toes for Diabetes
clawing of 92, 119, 128, 413 tricyclic antidepressants (TCA) 99, 101
surgical reconstruction 382–3 triglyceride (TG) levels, as diabetes‐related
toe tips, plantar pressure elevation 128 amputation risk factor 33
toe ulcers 132, 382, 404 trimethoprim 270
Tonga 87 truncal radiculopathy 90, 96
topical collagenases, wound cleaning 307 TSR see thermal stress response
total contact casts (TCCs) 130, 131, 145, T‐style anastomosis 467
214, 319, 320, 385–6, 485 TtFT see Train the Foot Trainer Project
total contact sockets 369 tumor necrosis factor (TNF) 317
touch perception 92 tuning forks, vibration perception
tourniquets, use of 353 44, 92, 113
Train the Foot Trainer (TtFT) Project type 1 diabetes 32
57–8 and amputation rates 35
training courses, Step by Step foot project, EURODIAB Prospective Complications
Brazil 64 Study 89
see also patient education neuropathy 314
tramadol 100 type 2 diabetes 32
TransAtlantic Inter‐Society Consensus and amputation rates 35–6
(TASC) II guidelines 250 neuropathy 314
transcriptional analyses 448 progenitor cell depletion 445
transcutaneous electrical nerve stimulation in Russian Federation 70
(TENS) 100, 218
transcutaneous oxygen tension measurement u
(TcPO2) 495–6 UAE see United Arab Emirates
transfemoral amputation 352, 361–2 Uganda, PAD prevalence 54
prosthetics 372 UK see United Kingdom

UKPDS see United Kingdom Prospective
Diabetes Study
ulcer, foot see diabetic foot ulcer
ulnar nerve entrapment 97
ultrasound (US) 170, 175
bypass surgery follow‐up 243
Duplex ultrasound 423, 496–7
endovascular revascularization 250
United Arab Emirates (UAE), diabetic foot
disease prevalence 79, 80
United Kingdom Prospective Diabetes Study
(UKPDS) 107
United Kingdom (UK)
amputation in 34, 35, 479
ethnic differences 37
costs of diabetic foot disease/
treatment 225
Diabetes UK 261
financial cost of DFU 9, 10
Indian Asians, diabetes‐related amputation
risk 35, 38
inpatient care 259–64
National Diabetic Foot Audit 425
see also England; Scotland
United States (US)
African Americans, diabetes‐related
amputation risk 37
amputation incidence/rates 34, 365, 479
DFU incidence 441, 459
diabetes incidence 169, 441
financial cost of diabetic foot disease/
treatment 9, 20–2, 170, 225
Hispanic Americans, diabetes‐related
amputation risk 37
hospitalizations for diabetic foot disease
4, 5, 260
National Inpatient Sample 4
Native Americans, diabetes‐related
amputation risk 35–7
unsteadiness
diabetic neuropathy 109, 144–5
during gait 195–6
patient perceptions of 148
therapeutic footwear 407
US see ultrasound; United States
Index 543
v
vacuum‐assisted wound closure device
(VAC) 353
vacuum suspension 370
valgus deformities see hallux valgus (bunion)
vancomycin 271, 272
Vanuatu 87
variation in health care 431–2, 438
varus deformities 334
vascular assessment 114, 463–4, 494–6
algorithms 498, 499, 500
vascular clinics 426
vascular control, diabetic foot ulceration
483–4
vascular dysfunction 445–7
vascular examination, DFI evaluation 290
vascular scientists 423
vascular surgeons 423, 426
vascular surgery consultation/evaluation
295–6, 460
vasculogenesis 446, 450
vasculopathy, radiography 157
vasodilatation 266
veins, bypass surgery 240–2
velcro closure, footwear 398
vibration perception 92, 112, 113, 114
Vibratip 114
Vitamin D deficiency 330
w
Wagner wound classification 2, 3, 6, 434
Wales, National Diabetes Foot Care
Audit 25, 303, 435–9
walkers see cast walkers
walking see gait
Walking Sense 205
Waterlow Score 262
WBC see white blood cell count
wearable technologies 203–4, 216–18, 415
see also footwear
weight‐bearing activity/exercise 196, 197, 348
Western Pacific region (WPR) 75–6
white blood cell (WBC) count 176, 177, 483
WIfI see Wound, Ischemia, and foot Infection
classification system
544 Index
wound care/healing 306, 308–9, 483
antiseptics 307
app 215–16
bioengineered products 464
clinical audit of foot care 434–5
clinical trial assessment 231
delays in healing 305
dressings 303–11
growth factors 444, 450
healing time 2, 303, 305
hospital readmission 239
impairment of 444–5
palliative care 239
and physical activity 214
post‐surgery 242, 243
pulsed radio frequency energy 218
reconstructive surgery 461
regenerative medicine 444–5
see also debridement
wound classification systems 2–3, 6, 9–10,
235, 236, 238, 243, 268, 291, 434
wound closure techniques, surgery 296–8
Wound, Ischemia, and Foot Infection (WIfI)
classification system 235, 236, 238,
243, 268
wound management, amputation
surgery 353
wound types 463
WPR see Western Pacific region
x
xenograft 464
X‐rays see radiography
z
Zambia
PAD prevalence 54
peripheral neuropathy prevalence 53