Article

Diabetic foot: Disease, complication

or syndrome?

Afsaneh Alavi, Mariam Botros, Janet L Kuhnke, David Armstrong,

Giuseppe Papia, Julia Lowe, Kevin Woo, R Gary Sibbald
Diabetes is the sixth leading cause of death in North America. The number of Citation: Alavi A, Botros M,
Kuhnke JL et al (2013) Diabetic foot:
Canadian with diabetes is projected to rise to 4.2 million people by 2020. Diabetic disease, complication or syndrome?
foot ulcers have been reported in 25% of individuals with diabetes and those with Diabetic Foot Canada 1: 13–7

foot ulcers have an increased risk of amputation and increased mortality. The earlier Article points
recognition of the high-risk foot and the timely treatment will save legs and lives. An 1. The 5-year mortality rate for
inter-professional approach is pivotal to support patients’ needs. people with a neuropathic ulcer
is higher than that of patients

D
iabetic foot complications are a challenge
that is growing worldwide. The care of
patients with such problems requires
an interprofessional approach within a complex
communication network for collaborative and
integrative care. Foot complications as a result of
diabetes cover a heterogeneous group of disorders
including neuropathy, foot deformity, ischemia,
chronic ulceration and Charcot foot.
Most diabetic foot abnormalities take an indolent
course, but the disease can lead to significant
disfigurement, adversely impacting daily life and
exposing patients to life threatening events, such
as infection (Jeffcoate et al, 2008) and ischemia
(Lipsky, 1997). The mortality rates associated
with complications following diabetic foot disease
are widely accepted to be equivalent to those of
aggressive forms of cancer (Armstrong, 2007;
Lavery et al, 2010; Armstrong and Mills, 2013). In
fact, the 5-year mortality rate for individuals with
a neuropathic ulcer is higher than that of patients
with Hodgkin’s disease, breast cancer or prostate
cancer. The 5-year mortality in individuals with
neuroischemic ulcers is even higher than in colon
cancer (Armstrong, 2007; Edmonds, 2010).
More than 20 Canadians are diagnosed with
diabetes every hour (CDA, 2009). The known
cases of diabetes in Canada represent 2.7 million
people (7.6%) in 2010, which is projected to rise
to 4.2 million people (10.8%) by 2020, but it is
estimated that an additional 700 000 persons have
the disease but are unaware and undiagnosed (CDA,
2009). In Canada, by 2019 that number is expected
with Hodgkin’s disease, breast
to grow to 3.7 million. (CDA, 2008). The Canadian cancer or prostate cancer.
economic cost of treating diabetic foot disease is 2. The treatment of diabetic
spiralling out of control. The Chronic Disease foot ulcers and their potential
Care Model (Improving Chronic Illness Care, complications is costly for
the healthcare system.
2012) supports systems, teams, and individuals
3. More emphasis should be
in delivering effective, evidence-based, outcome-
placed on maintaining the
focused services (Figure 1). health of people at risk of
While a diabetic foot ulcer is a personal crisis, diabetic foot disease rather
than simply dealing with
and a pivotal event in the life history of that patient,
complications when they occur.
it is also a financial challenge for the healthcare
system. The economic burden of diabetes in Canada Key words
was expected to be about $12.2 billion in 2010, - Diabetes
- Foot
and the direct cost of diabetes now accounts for - Immune function
about 3.5% of public healthcare spending and this - Ischemia
figure continues to rise (CDA, 2009). More than - Neuropathy
333 million people worldwide will develop diabetes
by 2025, creating a growing healthcare issue with a
huge cost burden (Narayan et al, 2003; Wild et al,
2004). People with diabetes have a 25% lifetime risk
of developing a foot ulcer with an annual incidence
of 2% (Abbott et al, 1998). Diabetic foot ulcers
are the most common reason for diabetes-related
hospitalisation.
The risk of lower extremity amputation in a
person with diabetes is 23-times higher than in
people without diabetes (Lavery and Armstrong,
2007). While amputation is the most preventable
complication of diabetic foot disease, it is preceded
by foot ulceration in more than 85% of major
amputations (Pecoraro et al, 1990).
Foot complications are also indicators of poor Authors
diabetic sugar control (elevated A1c) and other Author details can be found on
management issues, including elevated blood the last page of this article.

Diabetic Foot Canada Volume 1 No 1 201313

Diabetic foot: Disease, complication or syndrome?
“Foot complications are Figure 1. A schematic of the Chronic Disease Care Model (2012) support systems, teams, and individuals
also indicators of poor involved in delivering effective, evidence-based, outcome-focused services.
diabetic sugar control
(elevated A1c) and other The chronic care model
management issues,
including elevated blood Community
pressure, cholesterol,
Resources and policies
obesity, mental health,
and mood disorders Self-management support
(depression).”
Informed, activated Productive
patient interactions
Improved outcomes
pressure, cholesterol, obesity, mental health, and
mood disorders (depression).
There is a need to acknowledge that diabetic foot
abnormalities are a disease entity or syndrome similar
to retinopathy and nephropathy. We need to raise
awareness in healthcare providers and policy makers
concerning the person with diabetes and their increased
risk of foot ulcers, poor healing, and foot amputation.
A medical complication is an unfavorable evolution
of foot disease leading to a worsening of signs,
symptoms and/or new pathological changes. The
diabetic foot disease repair process is the product of
a well-orchestrated integration of complex events of
cell migration, cytokine production, angiogenesis and
extra cellular matrix deposition. These fundamental
processes are similar to tissue regeneration after
successful treatment of neoplasia. This raises the
question whether changes associated with the diabetic
foot represent a new disease phenomenon developing
in people with diabetes or whether they are a simple
complication of diabetes.
Etiology of diabetic foot complications
Diabetic foot changes are the result of several
contributory factors, such as peripheral neuropathy,
14
Health systems
Organisation of healthcare
Delivery Decision Clinical
system support information
design systems
Prepared, proactive
practice team
vascular changes and foot deformities. Assessment
and treatment of the contributing factors is essential
for optimal prevention and management (Boulton
et al, 2008; Bakker et al, 2011). This requires a
comprehensive foot examination, risk assessment
and clear communication with the individual as to
the status of their foot (Table 1).
Neuropathy and deformity
Damage to the nerve fibers is the result of
hyperglycemia, dyslipidemia, insulin resistance,
and oxidative stress, which can lead to cellular and
endothelial damage through different pathways
(Edmonds, 1986; 2010). Peripheral neuropathy leads
to both somatic and autonomic damage. The damage
to small fibers leads to a predominant loss of pain and
thermal sensation before blunting light touch and
vibration sensation (Edmonds, 1986; 2010).
The degeneration of postganglionic unmyelineated
axons further leads to dry skin or hypohydrosis. Dry
skin, thickness, and callus easily crack and this leads
to skin fissures.
Motor fibers are affected with slowed motor
conduction velocities and the reduced action
potential of the intrinsic muscles of the feet. This
Diabetic Foot Canada Volume 1 No 1 2013
 Diabetic foot: Disease, complication or syndrome?

“Multiple studies have

Table 1. Components of the foot exam (adapted from Boulton et al [2008]). demonstrated that more
Essential features of history Key components of the diabetic foot exam than 80% of patients
Past history Inspection with diabetic foot ulcers
• Ulceration Dermatologic
• Amputation • Skin status: colour, thickness, dryness, cracking have neuropathy.”
• Charcot joint • Sweating
• Vascular surgery • Infection: check between the toes for
• Angioplasty fungal infection
• Cigarette smoking • Ulceration
Neuropathic symptoms • Calluses / blistering: hemorrhage into callus
• Positive (e.g. burning or shooting pain,
electrical or sharp sensations, etc.)
• Negative (e.g. numbness, feet feel dead)
Vascular symptoms Musculoskeletal
• Claudication • Deformity (e.g. claw toes, prominent metatarsals heads,
• Rest pain Charcot joint)
• Non-healing ulcer • Muscle wasting (guttering between metatarsals)
Other diabetes complication Neurological assessment
• Renal (dialysis, transplant) • 10-g monofilament and one of the following four:
• Retinal (visual impairment) 1. Vibration using 128–Hz tuning fork
2. Pinprick sensation
3. Ankle reflexes
4. VPT (vibration perception threshold) testing
Vascular assessment
• Foot pulses; ABI (ankle–brachial index) if indicated

leads to the wasting and weakness of intrinsic
foot muscles and subsequent deformity (claw/
hammer toes). Foot deformities can cause an
abnormal distribution of plantar pressure, repeated
trauma, especially with poor fitting footwear,
and subsequent foot ulceration. This foot ulcer
formation is often the first step to subsequent
infection, local tissue necrosis and lower extremity
amputation.
Multiple studies have demonstrated that more
than 80% of patients with diabetic foot ulcers
have neuropathy. Neuropathy, not peripheral
arterial disease is considered to be the major factor
predisposing persons with diabetes to osteomyelitis
(Lipsky et al, 1990).
Non-enzymatic glycosylation of peri-articular soft
tissues may limit joint motion in the person with
diabetes, and neuropathy that can lead to atrophy
of the intrinsic musculature and subsequently
contracture of digits (Grant et al, 1990). This
decrease in the foot’s ability to accommodate for
ambulatory ground reactive forces increases plantar
pressures (Frykberg et al, 1998; Armstrong et al,
1999). Additionally, glycosylation may deleteriously
affect the resilience of the Achilles tendon, causing
shortening or loss of natural extensibility, resulting
in the foot being pulled into plantar flexion. The
subsequent increased forefoot pressure and even
mid-foot collapse can set the stage for a potential
Charcot arthropathy. Examination of the feet for
structural abnormalities and reduced joint mobility
is critical in helping identify pressure points that are
susceptible to future ulceration.
Ischemia
The underlying autonomic denervation may be
responsible for vascular abnormalities, with the
resting blood flow in a neuropathic foot five times
higher than in a normal foot. The increased arterial
flow to the limb leads to higher blood supply to the
bones and potential osteolytic abnormalities. Medial
wall calcification can cause arterial stiffness and
increased pulse wave velocity in a neuropathic limb.
Peripheral arterial disease (PAD) is present
in more than 50% of patients with diabetic
foot ulceration. Peripheral arterial disease is an
independent risk factor for further ulceration, and
neuroischemic diabetic foot ulcers are less likely
to heal and more likely to require amputation. It
is crucial to screen people with diabetes for PAD,

Diabetic Foot Canada Volume 1 No 1 201315

Diabetic foot: Disease, complication or syndrome?
“Deep and surrounding
tissue infection can be
a major threat to limb
and life and should be
treated promptly.”
Figure 2. A person with diabetes
who has developed a foot ulcer
due to the loss of protective
sensation and structural
deformities secondary to
neuropathy.
16
including conducting a thorough history and
physical examination in additional to noninvasive
vascular studies (Edmonds, 1986).
Coexisting polyneuropathy and PAD frequently
mask the symptoms of PAD and decrease the
sensitivity of vascular studies (Brownrigg et al,
2013). In people with diabetes, capillary hypo-
perfusion leads to a further delay in wound healing.
This delay in collateral formation and consequent
arterial occlusion may lead to severe perfusion
defects (Nabuurs-Franssen et al, 2002). Several
studies have demonstrated that diabetes is a risk
factor for the development of cardiovascular disease,
with risk of mortality twice as high in people with
diabetes; a foot ulcer further increases this risk
(Brownrigg, 2012).
Ulcers
People with diabetes are at risk of developing foot
ulcers due to the loss of protective sensation and
structural deformities secondary to neuropathy
(Figure 2). The diabetic foot is biologically
compromised and the major underlying cause
is deformity from peripheral neuropathy and
ischemia from peripheral arterial disease. Once skin
integrity is compromised, foot ulcers may lead to
other complications, partly due to a compromised
immune system.
Immune function abnormalities
Wound healing and neutrophil function are
impaired by hyperglycemia, necessitating good
glycemic control. In a study by Van den Bergh
et al, intensive intravenous insulin therapy was
administered to maintain blood glucose at or below
6.2mmol/L. The intravenous insulin reduced
morbidity and mortality among critically ill surgical
intensive care patients (Van den Berghe, 2001).
However, subsequent studies have failed to confirm
this observation. A meta-analysis, including NICE-
SUGAR study data (Griesdale, 2009) of intensive
insulin therapy and mortality among critically ill
patients, documented increased mortality related
to hypoglycemia. Most guidelines now recommend
adopting a more conservative approach with blood
glucose levels maintained between 7.8-11.1 mmol/L
(Umpierrez, 2012; CDA, 2013).
Deep and surrounding tissue infection can be a
major threat to limb and life and should be treated
promptly. Diabetic foot infection (DFI) is defined
clinically as a soft tissue or joint/bone infection
anywhere distal to the malleolus. It commonly
affects the toes followed by mid foot. Infection
usually starts with colonisation of neuropathic or
ischemic ulcers, or alternately may develop from
small fissures between the toes or nail beds. The
underlying ulcer base and surrounding tissues
are susceptible to bacterial colonisation and, with
decreased host resistance, critical colonisation and
possible subsequent deep and surrounding infection.
The progression from wound colonisation to
infection is influenced by various factors including:
• Type and depth of the wound.
• Blood supply.
• Immune status of the patient.
• Quantity and virulence of colonising organisms.
• Appropriateness of prevention and treatment.
DFI remains a challenge to manage because of
coexisting neuropathy, potential vascular changes,
diabetes-related immune deficiencies and foot
deformities.
Data from 14 hospitals in 10 European countries
demonstrated that 58% of diabetic foot ulcers in
1229 successive patients were infected, with 82%
infection rates in those admitted to hospital. Almost
half of the patients (45%) had deep ulcers that
extended into tissue below the subcutis, for example,
tendons, muscle or bone (Prompers et al, 2007).
Conclusion
Diabetes is the most common cause of non-
traumatic lower limb amputations (Armstrong
and Lavery, 1998; Rogers and Bevilacqua, 2010).
Foot ulcers and amputations reduce quality of life,
increase mortality and involve lengthy hospital
admissions (Rogers and Bevilacqua, 2010).
The diabetic foot is certainly a complex
multifactorial process that is more than an
associated disease complication. In order to
diminish the detrimental consequences associated
with diabetic foot complications we need an overall
structure that is designed to meet the needs of
patients requiring preventative and often chronic
maintenance care, rather than simply responding
to acute problems when they occur. We must
move from a reactive healthcare system to one
that keeps its people with diabetes-related foot
Diabetic Foot Canada Volume 1 No 1 2013

disease as healthy as possible, addressing their foot
care needs through planning, proven healthcare
delivery strategies and management. However,
once problems develop, these patients require
aggressive management involving a coordinated
interprofessional team with medical, wound and
vascular care, ideally in a single center.
In many European centers, integrated coordinated
care has greatly improved quality of life and patient
outcomes for people with diabetes. We need an
increased Canadian emphasis on the prevention and
management of diabetic foot disease. n
Authors
Afsaneh Alavi, Department of Medicine (Dermatology), University
of Toronto and Wound Care Center, Women College Hospital,
Toronto. Mariam Botros, Wound Care Center, Women College
Hospital, Toronto. Janet L Kuhnke, PhD Student, St Lawrence /
Laurentian University BSN Collaborative Program, Cornwall.
David Armstrong, Department of Surgery, University of Arizona
College of Medicine, Tucson AZ, USA. Giuseppe Papia,
Department of Vascular Surgery, University of Toronto and
Vascular surgery department, Sunny Brooks Hospital, Toronto.
Julia Lowe, Department of Medicine, Endocrinology Department,
University of Toronto, and Endocrinology Department, Sunny
Brooks Hospital, Toronto. Kevin Woo, School of Nursing,
Queen’s University, Kingston. R Gary Sibbald, Department of
Medicine (Dermatology), University of Toronto and Wound
Care Center, Women College Hospital and Public Health
Department, Dala Lana School, University of Toronto, Toronto.
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