Contents

 Learning Objectives
 Diabetes mellitus
– Physiological principles of metabolism
– Classification
– Etiology and pathogenesis
– Complications
– Management
 Thyroid and related disorders
 Disorders of pituitary gland

Learning objectives Physiological principles

 Differentiate among varying metabolic disorder and how  Insulin

they are clinically presented – Principle anabolic hormone
– Expands energy resources for inadequate times
– Mainly opposed by Catabolic hormones / analogues i.e.
 What are the treatment algorithms / therapeutic choices
 Adrenaline
for respective disorder
 Corticosteroids
 Glucagon
 Discuss patient related benefits and shortcomings for  Growth hormones
therapeutic agents
– Rapid acting; transports glucose & proteins across cell membrane
– Intermediate; potentiate metabolism via enzymes within a cell
– Long-term; increases complex molecules synthesis

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Physiological principles
 Insulin - Cellular functions
– Transport in adipose tissue depends on insulin
– Facilitates diffusion in liver, brain, kidney, and GIT
– Insulin dependent glucose transporters
– Liver uptakes amino acids with help of insulin
– Cells uptake potassium with help of insulin
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Physiological principles
 Insulin Cellular Functions
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Physiological principles
 Insulin Functions
– Insulin signaling in adipocytes and macrophages promotes fat
tissue expansion and inflammation
– Impaired insulin signaling in muscle causes insulin resistance
– Insulin resistance in the hypothalamus contributes to fasting
hyperglycemia and impaired appetite regulation
– Hepatocyte insulin resistance leads to increased glucose output
and dyslipidemia
– Insulin resistance in β-cells plays a role in progression of glucose
intolerance to type 2 diabetes mellitus
– Endothelial cell insulin resistance can limit insulin delivery to
target tissues
– Endothelial cell insulin resistance increases vascular wall
inflammation and atherosclerosis
– Insulin resistance in macrophages promotes necrotic core
formation in atherosclerosis
Physiological principles
 Insulin Cellular Functions
2
Physiological principles Physiological principles

 Insulin - Metabolic functions  Insulin - Availability vs. deficiency

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Physiological principles Physiological principles

 Insulin Deficiency  Insulin Deficiency

– Partial deficiency – Total deficiency
 Impaired glucose transport and uptake result in impaired glucose  Complete loss of insulin level cause osmotic pressure increase; may
clearance lead to neurological coma

 Post-prandial glucose load is not compensated leading to glucose  Perilipin increases production of free fatty acids to compensate for
level > 11 mmol / L energy requirements

 Glomerular filtrate exceeds renal threshold of glucose and glycosuria  Protein regulators mispercept the lack of glucose entry as
starts hypoglycemia and break in amino acids

 Glucose causes osmotic diuresis and polyuria  Glucose causes osmotic diuresis and polyuria

 Triglycerides levels rise secondary to improper uptake of plasma  Triglycerides levels rise secondary to improper uptake of plasma
lipids lipids

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Physiological principles Etiology and pathophysiology

 Pattern and Modulators of secretion – Primary diabetes

 Type 1 Diabetes Mellitus

 Type 2 Diabetes Mellitus

 Maturity Onset of Diabetes of Young

– Older patients need insulin at beginning

 Latent Autoimmune Diabetes in Adults

– Older patients need insulin at late stages

 Gestational Diabetes

 Pregnancy induced diabetes

– Secondary diabetes
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Etiology and pathophysiology Etiology and pathophysiology

 Primary diabetes  Primary diabetes

– Type 1 DM – Type 2 DM
 Islet beta cells of pancreas are completely lost  Absolute insulin deficiency

 Autoantibodies are found up to 15 years causing pre-diabetes syndrome  Relative insulin deficiency

 80% patients express high titter of beta-cell specific antibodies  Insulin receptor dysregulation

 Anti-islet antibody don’t affect insulin producing cells  Insulin resistance and hyperinsulinema

 T-Cells invade islets causing inflammatory changes that cause insulititis  Most patients are obese prior to the disease and frequent complaint is of
abrupt weight loss
 10% of beta cells somehow survive until clinical onset of disease
 Abnormal amylin secretion are observed prior to the course of disease
 Most cases are precipitated by infection
 Abdominal obesity, hyperinsulinaemia, insulin resistance,
 HLA 15
hyperlipidaemia, type 2 diabetes and hypertension = metabolic syndrome
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Etiology and pathophysiology Presentation

 Secondary diabetes  Direct consequences of High Blood Glucose

– Polyuria, frequency, nocturia, polydipsia (osmotic diuresis)

– Visual disturbance (osmotic changes to intra-ocular pressure)

– Urethritis, pruritus vulvae, balanitis (urogenital infection)

 Metabolic consequences of Impaired Glucose Tolerance

– Lethargy, weakness, weight loss

– Increased fat metabolism

 Long-term consequences of Hyper-glycemia and –lipidemia

– Vascular disease, heart disease, renal disease, neuropathy, eye
disease, infections, arthropathy
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Complications Complications

 Acute Complications  Acute Complications

– Hyperglycemia
 Missed antidiabetic dose
 Hyperglycemic drugs; thiazides steroids
 Excess dietary intake
 Metabolic stress; infection, pregnancy
– Hypoglycemia
 Excess dose
 Potentiation of oral hypoglycemia (drug interaction)
 Missed meal; dieting
 Unexpected physical activity
 Excessive tight blood glucose control

 Adrenergic – enhanced sympathetic activity

– Tremor, sweating, shivering
– Anxiety, palpitations
 Neurologic – reduced CNS glucose
– Drowsiness, disorientation, confusion
– Aggression, convulsions, coma, brain insult
 Multiple effects
– Hunger, salivation, blurred vision

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Treatment overview Treatment

– Type 1 DM – Type 1 DM
 Rapid Acting  Intensive insulin treatments control BGL effectively than conventional
 Short Acting
 Intermediate Acting  Patients can be started form 0.1U of insulin / kg body wt
 Long Acting
 Hypoglycemia is demotivational factor for compliance
– Type 2 DM
 Biguanides  Localized fat hypertrophy may occour
 Sulfonylureas
 Meglitinides  Rarely urticaria, angioedema, rashes, localized erythema
 α-Glycosidase inhibitors
 Thiazolidinediones  Rarely immune mediated insulin resistance may be managed by
 Dipeptidyl peptidase-4 inhibitors human insulin
 Sodium-glucose co-transporter 2 inhibitors
 Glucagon-like-peptide analogue

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Treatment Treatment

– Type 1 DM
– Intensive Multiple Dose Insulin Regimens
 R; Aspart; Glulisine; Lispro before meal
And
 N; Glargine; Detemir at bed time
 Flexible; usually good BGL control
OR
– Type 2 DM
– Biguanides (Metformin)
 Lowers blood glucose by decreasing hepatic glucose production
 Reduces A1c by about 1.5%
 Does not stimulate insulin secretion; does not cause hypoglycaemia
 Weight stability or mild weight loss
 Low dose can be safely added to lactating mothers
 Nausea, anorexia and diarrhea; B-12 deficiency; lactic acidosis

Drug Formulation Minimum Dose Maximum Dose

 R; Aspart; Glulisine; Lispro before meal
Initial dose 500mg OD
And Metformin 500mg 1000mg TID
Usual Dose 1500mg OD
 N; twice daily at breakfast and supper or bed time Metformin SR 850mg Usual Dose 850mg OD 850mg TID
 Better for people with varying schedules Metformin XR 500mg
Initial dose 500mg OD
2000mg OD
Usual Dose 2000mg OD

– Continuous Subcutaneous Insulin Infusion

– Conventional Insulin Regimen
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Treatment Treatment

– Type 2 DM – Type 2 DM
– Sulphonylureas (SU) – Meglitinides
 Reduce plasma glucose by increasing insulin secretion  Short acting insulin secretagogues
 Average A1c reduction of 1.5%  Reduce A1c by 1.0-1.2%.
 Second gen SUs cause less risk of hypoglycaemia and less weight  Shorter half-life than SUs
gain  Peak level 1-hour post administration
 Hypoglycaemia; Weight gain  Eliminated within 4 – 6 hours
 Highly protein bound  Less risk of weight gain and hypoglycemia compared to SUs
 Prime use to control postprandial hyperglycaemia
Drug Formulation Minimum Dose Maximum Dose
Glibenclamide 5mg 2.5mg OD 10mg BD Drug Formulation Minimum Dose Maximum Dose
Gliclazide 80mg 40mg OM 160mg BD 0.5mg 4mg
Repaglinide 0.5mg/1mg/2mg
With main meals Not exceeding 16mg/day
Gliclazide MR 60mg 30mg OM 120mg OD
60mg 120mg
Nateglinide 120mg
Glipizide 5mg 2.5mg OD 10mg BD With main meals Not exceeding 360mg/day
Glimipride 2mg/3mg 1mg OM 6mg OM

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Treatment Treatment

– Type 2 DM – Type 2 DM
– α-Glucosidase Inhibitors (AGIs) – Thiazolidinediones (TZDs)
 Inhibits α-glucosidase enzymes in intestine  Increase insulin sensitivity in muscle, adipose tissue & liver
 Reduces A1c by 0.5–0.8%  Reduce A1c by 0.5–1.4%
 Reduces rate of absorption of polysaccharides  Improvement in glycaemic control seen after six weeks
 Lowers postprandial glucose without causing hypoglycaemia  Redistribution of body fat, fluid retention, heart failure, macular
 Bloating, abdominal discomfort, diarrhoea and flatulence oedema and osteoporosis.
 Contraindicated in patients with CCF & liver failure
Drug Formulation Minimum Dose Maximum Dose
Initial dose 50mg OD
Drug Formulation Minimum Dose Maximum Dose
Acarbose 50mg/100mg Usual dose 50mg – 100mg 100mg TDS
To be given during meals Pioglitazone 15mg/30mg 15mg OD 45mg OD
Rosiglitazone 4mg/8mg 4mg OD 8mg OD

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Treatment Treatment

– Type 2 DM – Type 2 DM
– Dipeptidyl Peptidase-4 (DPP-4) Inhibitors – Sodium-glucose Co-transporter 2 (SGLT-2) Inhibitors
 Increase stability of glucagon-like-peptide by inhibiting dipeptidyl  Selectively inhibit SGLT-2, reducing glucose reabsorption leading to
peptidase-4 increase urinary glucose excretion
 Lower A1c by 0.5–0.8%  Reduces A1c by 0.7%
 Weight neutral and minimal risk of hypoglycaemia  Weight and modest blood pressure reduction together with lower risk
 Saxagliptin associated with increased risk for heart failure of hypoglycaemia
 Contraindicated in patients ē medullary thyroid carcinoma  Side effects include significant increased of genitalia and urinary
tract infection.
Drug Formulation Minimum Dose Maximum Dose  Not recommended in patients with moderate to severe renal
Sitagliptin 25mg/50mg/100mg 50mg OD 100mg BD impairment (eGFR <60 mL/min/1.73 m2)
Vildagliptin 50mg 50mg OD 50mg BD Drug Formulation Minimum Dose Maximum Dose
Saxagliptin 2.5mg/5mg 2.5mg OD 5mg BD Dapagliflozin 5mg/10mg 5mg OD 10mg OD
Linagliptin 5mg 5mg OD 5mg BD Canagliflozin 100mg/300mg 100mg OD 300mg OD
Alogliptin 6.25mg/12.5mg/25mg 6.25mg OD 25mg BD Empagliflozin 10mg/25mg 10mg OD 25mg OD

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Treatment Treatment

– Type 2 DM  Recommendations
– Glucagon-like Peptide-1 (GLP-1) Receptor Agonists – Metformin
 Exenatide IR / XR  Efficacious, low risk of hypoglycaemia and weight neutral
– Subcutaneously; IR BID; XR OD
– SU, Glinides, Insulin
– IR reduces A1c by 0.5–1.0%
 Efficacious, risk of hypoglycaemia and weight gain
– Exenatide reduces A1c up to 1.5%
 Liraglutide – DPP-4i
– Reduces mean A1c up to 0.8 to 1.4%  Moderate efficacy, low risk of hypoglycaemia, weight neutral
 Lixisenatide – GLP-1 RA, SGLT-2i
– Reduction in A1c of 0.5-0.7%  Moderate efficacy, low risk of hypoglycaemia and weight loss
Drug Formulation Minimum Dose Maximum Dose – TZD
Exenatide IR
5µg/20µL
5µg BD 10µg BD
 Moderate efficacy, low risk of hypoglycaemia and weight gain
10µ/40µL
– AGI
Exenatide XR 2mg 2mg weekly 2mg weekly
 Modest efficacy, low risk of hypoglycaemia, weight neutral
Laraglutide 6mg/mL 0.6mg OD 1.8mg OD
50µg/mL
Lixisenatide 10µg OD 20µg OD
100µg/mL

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 Treatment Treatment

 Recommendations  Recommendations
Diagnosis of Type 2 Diabetes Glycemic A1c 6.5–< 7.5% A1c 7.5–<8.5% A1c 8.5–10.0% A1c >10.0%
Lifestyle Modification Control OR OR or or
Current FPG 6–<8mmol/L FPG 8–<10mmol/L FPG 10–13 mmol/L FPG >13 mmol/L
Treatment
A1c < 6.5% AND A1c 6.5 – <7.5% OR A1c 7.5 – <8.5% OR A1c 8.5 – <10.5% OR A1c >10.5% OR
FPG <6mmol/L FPG 6 – <8mmol/L FPG 8 – <10mmol/L FPG 10 – <13mmol/L FPG >13mmol/L Lifestyle Treatment Add Metformin (or if Add Metformin and Add Metformin and Dual or Triple therapy
metformin cannot be another agent (Dual another 2 agents not + insulin (basal or
Lifestyle Approach OAD Monotherapy Dual Combination Triple Therapy Combination therapy tolerated add either therapy) used for the dual premixed)
+ basal/premixed SU/Glinides/AGI/TZD/ therapy (Triple
PP > 11mmol/L, then Metformin OR Metformin with Metformin with insulin therapy DPP-4i/GLP-1 RA/ therapy)
SGLT2i
Metformin SU SU SU Intensive insulin
therapy + OAD Monotherapy Add another agent Add 2 agents not used Dual or Triple therapy Optimise insulin (basal
Glinides Glinides Glinides Glinides (Dual therapy) for the dual therapy + insulin (basal or plus/multiple
(Metformin
preferred) (Triple therapy) premixed) premixed) ± OAD
AGI AGI AGI AGI
Dual Therapy Add another agent Dual or Triple therapy Optimise insulin (basal Intensify insulin (basal
DPP-4I TZD TZD TZD
not used for the dual + insulin (basal or plus/multiple bolus/multiple
DPP-4I DPP-4I DPP-4I therapy (Triple premixed) premixed) ± OAD premixed) ± OAD
therapy)
GLP-1 RA GLP-1 RA GLP-1 RA
Triple Therapy Dual or Triple therapy Optimise insulin (basal Intensify insulin (basal Intensify insulin (basal
SGLT-2I SGLT-2I SGLT-2I + insulin (basal or plus/multiple bolus/multiple bolus/multiple
premixed) premixed) ± OAD premixed) ± OAD premixed) ± OAD
Insulin Insulin
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Treatment Treatment

 Recommendations  Insulin in T2DM

Onset of Peak Action
Insulin preparation Administration timing
action action duration
Prandial
Normal Weight Overweight Obese Hypoglycemia risk Stage 3 CKD onwards Short acting, R 30–60 mins 2–4 hours 6–10 hours 30 minutes before meal
Rapid analogue 0–20 mins 1–3 hours 3–5 hours 5–15 minutes before meal
Metformin Metformin Metformin Metformin Metformin - ½ dose
Basal
DPP-4i SGLT-2i GLP-1 RA* Metformin with DPP-4i 1–2 hours 4–8 hours 8–12 hours Pre-breakfast/Pre-bed
Intermediate acting, NPH
SGLT-2i DPP-4i SGLT-2i SGLT-2i Sulfonylurea - 3rd gen Long acting analogue
Sulfonylureas GLP-1 RA* Basal insulin Thiazolidinediones Prandial Insulin
Glargine 30–60 mins - 16–24 hours Same time everyday
Detemir 30–60 mins - 16–24 hours Flexible once daily injection
GLP-1 RA* Basal/premix insulin Insulin intensification GLP-1 RA* Basal insulin Degludec 30–60 mins - 24–40 hours Maximum interval up to 40 hours

Basal/premix insulin Insulin intensification Basal insulin Premix Insulins

Mixtard 30 30 mins Dual 18–23 hours 30–60 minutes before meal
Humulin 30 mins Dual 16–18 hours 30–60 minutes before meal

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Treatment Gestational diabetes

 Monitoring  Diabetes prior to pregnancy

– Glycaemic targets must be individualized – Pregnancy must be planned

– If achievable without significant hypoglycemia, target to achieve – HbA1c shall be kept near to target
an A1c ≤6.5%
– BP shall be maintained , 130/80 mmHg
– Fasting or pre-prandial BGL of 4.4 to 6.1 mmol/L
– Shift form OAD to insulin
– Two-hour BGL targets of 4.4 to 8.0 mmol/L
– Shift general anti hypertensives to pregnancy safe
– Patients on insulin are recommended, and on OAD are desired to
SMBG – Screen chronic micro & macro vascular complications

– Glycemic control, comorbidities, complications and CVD risk

factors should be evaluated at initial visit & whenever indicated

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Gestational diabetes Gestational diabetes

 Diabetes during pregnancy  Treatment

– Risk Factors – Multiple dose basal bolus is recommended
 25 years or older
– Daily-dose, multiple, short-acting Human insulin
 BMI > 27
– Rapid acting preprandial for better 1 hour postprandial BGL
 History of obstetric disorders
– Detemir may be better in case of nocturnal hypoG
 History of macrosomic baby or gestational DM

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MODY MODY

 Most common form of DM in adolescents worldwide  Treatment algorithm

Diagnosis of diabetes in an adolescent

 Usually occur in 2nd decade of life Asymptomatic; Symptomatic; Acidosis

HbA1c <9%; HbA1c >9%
No acidosis No acidosis
Insulin as in T1DM
 Pubertal insulin resistance main cause for T2DM until acidosis is
resolved
Metformin; Basal insulin;
Lifestyle change Metformin; Likely type 1
Lifestyle change
 Pancreatic autoantibodies main cause for T1DM Initiate MDI insulin;
Educate

T1DM overlapping T2DM T2DM overlapping T1DM Diabetes antibodies

Positive Negative
Non obese adolescents with diabetes Impression of obesity at onset
Continue metformin; Continue or start
Wean insulin MDI insulin;
Positive pancreatic autoantibodies Low detection of autoantibodies Educate
Yes
At target
Presence of ketosis on presentation Monogenic diabetes No
Basal insulin – titrate to max 1.2 u/kg/day

Yes No
At target
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MODY Complications (Acute)

 Treatment Recommendations  Hypoglycemia

– Set treatment targets as DM in adults – Low blood glucose level
– OAD safety and efficacy not established  BGL < 4.0mmol/L
 BGL < 3.0mmol/L
– Options available are
 Metformin – Autonomic neurologic symptoms are present
– Start metformin with 500 mg/d for 7 days  Trembling Difficulty concentrating
– Increase 500 mg once a week over 3-4 weeks  Palpitations Confusion
– Maximal dose of 1000 mg bid  Sweating Weakness
 Anxiety Drowsiness
 Insulin  Hunger Vision Changes
– Required for initial metabolic control
 Nausea Difficult speaking
– Switch to metformin when metabolically stable
 Tingling Headache/ Dizziness
– Long/intermediate-acting at 0.5 u/kg/d at bed-time
– Upto 1.2 u/kg

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Complications (Acute) Complications (Acute)

 Hypoglycemia  Hypoglycemia
– Risk factors – Treatment Goal
 Advance age  detect and treat a low blood glucose level promptly
 Severe cognitive impairment  eliminate the risk of injury to oneself and to relieve symptoms quickly
 Poor health knowledge  avoid overcorrection of hypoglycaemia especially in repeated cases
 Increased A1c  may lead to poor glycaemic control and weight gain
 Hypoglycaemia unawareness
 Long standing insulin therapy
 Renal impairment
 Neuropathy

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Complications (Acute) Complications (Acute)

 Hypoglycemia  Hypoglycemia
– Grading and Treatment – Grading and Treatment
 Mild  Severe
– Presence of autonomic symptoms – Presence of autonomic symptoms
– Self-treat – Patient can’t self ambulate; unconscious; BGL < 2.8

 Moderate  20 – 50cc D50% over 1 – 3 mins

– Presence of autonomic and neuroglycopenic symptoms  1 TBS of honey in oral cavity
– Self-treat
 Give regular meals and snacks after BGL > 4 mmol / L
 15 gm / 1 TBS of simple carbohydrates/sugar
 1 TBS of honey
 ¾ cup of juice

 Check BGL; repeat if BGL <4.0 mml/L after 15 minutes

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Complications (Acute) Complications (Acute)

 Hyperglycemia – HHS  Hyperglycemia – HHS

– A hyperglycemic episode is considered HHS when – Management
 Underdiagnosed Hypovolemia  Expand plamsa volume by crystalloid
– 0.9% NS; if patient is not in hemodynamic or cardiogenic shock
 BGL above 30mmol/L – 0.45% NS; if osmolality is not restored despite adequate hydration

 Serum Osmolality > 320 mosmol/kg  Anti-coagulants shall be used pertaining to hydration and electrolyte
status
 Serum Osmolality =2(Na+ + K+) + Glucose + Urea
 Insulin use in controversial; use insulin if BGL does not dissipate
after IV resus
– Presentation
 Hypertonic muscle appearance suggest good volume

 Absence of ketones, and ketone induced acidosis

 Severe cognitive impairment secondary to cerebral edema

49 50

Complications (Acute) Complications (Acute)

 Hyperglycemia – DKA  Hyperglycemia – DKA

– A hyperglycemic episode is considered HHS when – Pathophysiology
 Hyperglycemia
– ≥ 11.1 mmol • L-1
Pathophysiology Systemic Effects Metabolic Derangement Presenting Features

 Presence of ketones Decreased production Hyperglycemia

of insulin
– Urine Increased hepatic Dehydration
OR
Polydipsia
– Blood Peripheral insulin glucose production,
Polyurea
resistance Decrease
peripheral glucose Drowsiness
utilization Imbalanced
 Acidosis Electrolytes

– pH below 7.3
Ketogenesis
– HCO3 below 21 mmol • L-1
Tachypnoea
Increased Kussmaul
triglyceride Breathing
Increased production breakdown Vomiting
of; Increased formation Abdominal Pain
Hormone Sensitive of ketone bodies Disorientation
Lipase, Coma
Catecholamines, Acidosis
Glucagon, Cortisol
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Complications (Acute) Complications (Acute)

 Hyperglycemia – DKA  Hyperglycemia – DKA

– Treatment objectives – Treatment
 Correction of hyperglycemia
– Insulin
» Intravenous dilution
» Basal bolos
» Subcutaneous

 Correction of hypovolemia
– Crystalloids
» Normal saline
» Potassium, Dextrose
– Colloidals
» Gelafundin, Albumin

 Correction of acidosis
53 54

Complications (Acute) Complications (Acute)

 Hyperglycemia – DKA  Hyperglycemia – DKA

– Pretreatment complications of DKA – Counter-measures for DKA treatment complications
 Infection  Hypoglycemia
– Leukocytosis is a stress response – Switching between scales
– Crosscheck the band count – Dextrose as a dilution solution
– Correlate with hematocrit
 Hypokalemia
 Hyperkalemia – GIK
– Altered ICF/ECF potassium
– Pseudohyperkalemia  Hypervolemia
– pH based adjustment – Down-titration of IV volume
– Avoid using colloidal solution
 Hypovolemia
– Use varying dilutions of normal saline
– Use colloidal solutions

 Cardiac and renal manifestations

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Complications (Acute) Complications (Chronic)

 Hyperglycemia – HHS/DKA – EYES

– Treatment Goal  Retinopathy, glaucoma, cataract; blindness
 Expect patient to sit, and eat and drink with back-to-insulin
– Nerves
 If hyperglycemia is not resolved, identify and treat the reasons for  Sensory, autonomic and motor defects
failure to respond
– Renal
 Convert to subcutaneous regime when biochemically and  Glomerulosclerosis; chronic renal failure
hemodynamically stable, and the patient is ready and able to eat

– Macrovascular
 Cardiac continuum

– Locomotor
 Slow-healing peripheral lesions; ‘the diabetic foot’; amputations; stiffness

– Immune
57 58
 Increased susceptibility to infection

Complications (Chronic) Complications (Chronic)

 Neuropathy  Neuropathy
– Type 1 NP – Type 1 NP
 Peripheral Neuropathy  Management
 Focal or diffused – Glycemic control is only therapy
 As many as 50 – 80% patients – Pain and sensory neuropathy
» Pregabalin; 150-600mg/day
– Diagnosis » Gabapentin; 300-1200mg; tid
 10-g monofilament test in addition to » Valproate; 500-1000mg/day
 Pin prick » Duloxetine; 60-120mg/day
 128-Hz tuning fork vibration » Tramadol; 100-400mg/day
 Ankle reflexes » Venlafaxine; 75-225mg/day
 Biothesiometer

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Complications (Chronic) Complications (Chronic)

 Neuropathy  Sexual dysfunction (Male)

– Type 2 NP – Inability to achieve, maintain or sustain an erection firm enough
 Autonomic Neuropathy for sexual intercourse
 Highly related to CV related mortalities
– May result from psychological, neurologic, hormonal, arterial, or
– Presenting Complaints cavernosal impairment or from a combination
 Resting tachycardia and Orthostatic HTN
 Gasrtoparesis and constipation – Treatment
 Erectile dysfunction  PDE-5 inhibitors can be used
– Sildinafil; 50-100mg; 60 mins pre-coitus
– Management – Tadalafil; 5-20mg; 30 mins pre-coitus OR 2.5mg daily
 Gastroparesis - Midodrine  Dopamine agonist
 Orthostatic hypotension – Metoclopramide – Apomorphine; 2-3mg; 10 mins pre-coitus (sublingual)

 Diabetic diarrhea - Loperamide  Prostaglandin

– Alprostadil; 125-1000µg; 5 mins pre-coitus (suppository)
 Erectile dysfunction - PDEi
– Alprostadil; 60µg; 50 mins pre-coitus (injection)
61 62

Complications (Chronic) Complications (Chronic)

 Sexual dysfunction (Female)  Diabetic foot ulcer

– Decreased sexual interest/arousal, orgasmic disorder and genito- – Pathophysiology
pelvic pain  Ischemia
– Altered blood flow
– May result from psychological, neurologic, hormonal, arterial, or
cavernosal impairment or from a combination  Neuropathy
– Pyelol deposition

– Treatment
 Postmenopausal women  Immunological effects
– Defects in macrophage response to insulin
– Tibolone; 2.5mg; OD

 Premenopausal women
– Bupropion; 150mg; bid

 Topical lubricants and vaginal moisturizers

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Complications (Chronic) Complications (Chronic)

– Presentation (Physical) – Presentation (Clinical)

 Abscess  Symptoms
– Involves central plantar space caused by trauma – Neuropathic patients do not feel pain; come for swelling/balance issues

 Cellulitis  Signs
– Mainly involves dorsal areas of routine care i.e. nails, nail beds – Erythema, edema, presence of pus, drainage of sinuses
– Foul odor may suggest anaerobic bacteria
 Mal perforans ulcer
– Usual ulcer of thickened hardened calluses of sole  Laboratory
– Deep intraoperative samples of debridement shall be taken
 Osteomyelitis
– Neuropathy associated misalignment of weight bearing bones

65 66

Complications (Chronic) Complications (Chronic)

– Bacteria – Treatment on basis of presentation classification

 Aerobes 63%–75%  Mild
– Presentation
– Gram-positive 42%–64% » Purulence; erythema; pain; tenderness; cellulitis

– Gram-negative 16%–18%  Treatment

– G +ve coverage; 1 – 2 weeks
 Anaerobes 25%–40% » Cephalexin; 250 – 500mg qid
» Clindamycin; 150 – 300mg qid; IV 450 – 600mg tid
» Cloxacillin; 250 – 500mg qid
» Cotrimoxazole; 800/160mg bid

 Monitoring
– 3 – 5 days follow up for reassessment
– Biopsy recommended if no improvement

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Complications (Chronic) Complications (Chronic)

– Treatment on basis of presentation classification – Treatment on basis of presentation classification

 Moderate  Moderate and Severe 2 – 6 weeks
– Presentation – Cefuroxime; IV 100 – 150mg/kg in 3 doses; max 750mg
» Infection as in mild; cellulitis > 2cm; abscess – Piperacillin/tazobactam; IV 3/0.375gm qid
» Bone and/or joint are involved – Clindamycin; IV 450 – 600mg qid
– Ciprofloxacin; 500 – 750mg bid
 Severe – Vancomycin; IV 1gm bd
– Presentation
» Infection as in mild – Metronidazole; 500mg bid
» Abscess and cellulitis as in moderate
» Metabolic instability
» Significant leukocytosis
» Hyperglycemia up to confusion

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Complications (Chronic) Complications (Chronic)

 Cardiovascular diseases  Nephropathy

– CV Diseases manifested by DM – Treatment
 Myocardial Ischemia and Infarction  Treat microalbuminuria or overt proteinuria even if BP is <135/75 mmHg
 Heart Failure
 An ACEI or ARB is preferred and may normalize microalbuminuria even
– CV diseases manifested by DM induced diseases with optimal BP control
 Hypertension
 Dyslipidemia  Normalizing microalbuminuria may reduce decline in GFR
 Obesity
 Reduce protein intake to 0.8 g/kg/day in stage III & IV diabetics and to
0.6–0.75 g/kg/day in ESRD diabetics
– Independent CVD risk factors in DM patients
 Smoking
 Reduction in protein intake may delay progression of renal impairment.
 Age > 60 years
 Poor lifestyle; lack of exercise

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