---

Diabetes Mellitus - 15 Marks (Physiotherapy Exam)

---

1. Definition

• Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
• It leads to disturbances in carbohydrate, fat, and protein metabolism.

---

2. Classification (ADA Criteria)

---

3. Pathophysiology

• Autoimmune T-cell mediated destruction of islets of Langerhans
• Autoantibodies: islet cell antibodies, anti-insulin, anti-GAD65, anti-IA-2
• Results in absolute insulin deficiency
• Genetic susceptibility (>60 loci identified) + environmental trigger (enteroviruses)

• Central defect: insulin resistance (impaired insulin-mediated glucose uptake)
• Compensatory hyperinsulinemia → progressive beta cell exhaustion
• Increased hepatic glucose production
• Obesity is a major contributory factor

---

4. Clinical Features (Signs & Symptoms)

• Polyuria - osmotic diuresis due to glycosuria
• Polydipsia - compensatory increased thirst
• Polyphagia - cellular starvation despite hyperglycemia

• Unexplained weight loss
• Fatigue and weakness
• Blurred vision (lens changes with glucose fluctuations)
• Recurrent infections (fungal, UTI, skin)
• Slow wound healing
• Numbness/tingling in hands and feet (early neuropathy)

---

5. Diagnostic Criteria (ADA)

• Diagnosis requires two abnormal tests in asymptomatic patients, or one test + symptoms
• HbA1c target for treatment: <7%

---

6. Complications

Microvascular (due to direct hyperglycemia damage):

• Diabetic Retinopathy - leading cause of blindness; microaneurysms, cotton wool spots, proliferative changes
• Diabetic Nephropathy - leading cause of end-stage renal disease (ESRD); affects 20-40% of diabetics
• Diabetic Neuropathy - peripheral sensorimotor + autonomic neuropathy; numbness, pain, loss of reflexes

Macrovascular (accelerated atherosclerosis):

• Coronary artery disease (CAD)
• Cerebrovascular disease (stroke)
• Peripheral arterial disease (PAD) - risk for diabetic foot/gangrene

Other complications:

• Diabetic foot ulcers
• Autonomic neuropathy (postural hypotension, gastroparesis, neurogenic bladder)
• Diabetic ketoacidosis (DKA) - Type 1 emergency
• Hyperosmolar hyperglycemic state (HHS) - Type 2 emergency

---

7. Management

A. Lifestyle Modifications:

• Diet control: low glycemic index, reduced refined carbs
• Regular aerobic exercise (150 min/week) - improves insulin sensitivity
• Weight reduction in Type 2 DM

B. Pharmacological:

• Type 1 DM: Insulin replacement (basal-bolus regimen) - mandatory
• Type 2 DM (stepwise):
  • 1st line: Metformin
  • Add-ons: Sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors
  • SGLT-2 inhibitors reduce CV death and HF hospitalization
  • GLP-1 agonists reduce MACE (major adverse CV events)
  • Insulin when oral agents fail or in DKA/HHS

C. Targets:

• HbA1c < 7%
• Premeal glucose: 80-130 mg/dL
• Postprandial glucose: <180 mg/dL
• BP <130/80 mmHg

---

8. Physiotherapy Relevance

• Exercise prescription: Aerobic exercise + resistance training improve glycemic control and insulin sensitivity
• Diabetic neuropathy management: Balance training, sensory re-education, fall prevention
• Diabetic foot care: Regular assessment, offloading, wound care assistance
• Post-amputation rehabilitation: Prosthetic training, gait re-education
• Cardiovascular rehabilitation: Supervised exercise in CAD/peripheral vascular disease
• Autonomic neuropathy precautions: Monitor BP changes during exercise, watch for hypotension
• Peripheral arterial disease: Graded walking program for claudication
• Pre-exercise screening: Check blood glucose before exercise; avoid exercise if glucose <100 mg/dL or >250 mg/dL
• Patient education: Foot inspection, footwear advice, lifestyle counseling

---

---

Complete Management of Diabetes Mellitus

---

GOALS OF MANAGEMENT

• Relieve symptoms of hyperglycemia
• Prevent acute complications (DKA, HHS, hypoglycemia)
• Prevent/delay chronic microvascular and macrovascular complications
• HbA1c target: <7% (general); <6.5% in young patients; 7-8% in elderly/high-risk
• Fasting glucose: 80-130 mg/dL | Post-meal glucose: <180 mg/dL
• BP target: <130/80 mmHg | LDL target: <70 mg/dL (high CV risk)

---

A. NON-PHARMACOLOGICAL MANAGEMENT

1. Medical Nutrition Therapy (Diet)

• Reduce refined carbohydrates, concentrated sweets, saturated fats
• Mediterranean diet or DASH diet - best evidence for CV risk reduction
• Moderate carbohydrate intake; increase dietary fiber
• 5-10% weight loss target in overweight/obese T2DM
• Avoid very low-carb diets if on SGLT2 inhibitors or insulin (risk of DKA)
• Caloric restriction + dietary counseling by registered dietician (quarterly follow-up)

2. Physical Activity

• Minimum 150 min/week of moderate-intensity exercise (50-70% max HR)
• Brisk walking 30 min/day improves insulin sensitivity and glycemic control
• Resistance/strength training 2-3x/week in addition to aerobic exercise
• Exercise reduces HbA1c by ~0.6-0.7% independently
• Precautions:
  • Check blood glucose before exercise
  • Avoid if glucose <100 mg/dL (hypoglycemia risk) or >250 mg/dL with ketones
  • Avoid vigorous exercise in proliferative retinopathy (risk of hemorrhage)
  • Peripheral neuropathy: increased fall/foot injury risk

3. Weight Management

• Every 1 kg of weight loss reduces T2DM risk by ~15%
• 7% body weight loss + exercise reduces DM incidence by ~60% in prediabetes
• Bariatric surgery: For BMI >35 with T2DM - can cause remission; options: Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding

4. Diabetes Self-Management Education (DSME)

• Structured patient education improves HbA1c by ~1%
• Covers: diet, exercise, SMBG, medication adherence, foot care, sick-day rules
• 7 core behaviors: diet, physical activity, blood glucose monitoring, medication adherence, problem solving, coping, risk reduction

5. Smoking Cessation

• Smoking worsens insulin resistance and accelerates all diabetic complications
• Cessation reduces CV risk and slows progression of nephropathy

---

B. PHARMACOLOGICAL MANAGEMENT

TYPE 1 DIABETES - Insulin is MANDATORY

Insulin Types & Regimens

Standard Regimen - Basal-Bolus:

• Basal insulin (Glargine/Detemir): 40-50% of total daily dose (TDD) once daily
• Bolus (rapid-acting) insulin: given before each meal (remaining 50-60% TDD split 3 ways)
• Total daily dose typically: 0.5-1.0 units/kg/day

Insulin Delivery Devices:

• Syringes, insulin pens (most common)
• CSII (Insulin pump): Continuous subcutaneous infusion of rapid-acting insulin
• Closed-loop system (Artificial Pancreas): Sensor + pump + algorithm; reduces hypoglycemia; recommended for most T1DM patients

---

TYPE 2 DIABETES - Stepwise Approach

Step 1: Lifestyle Modification + Metformin (FIRST LINE)

• Mechanism: Reduces hepatic glucose output; improves insulin sensitivity; reduces intestinal glucose absorption
• Dose: Start 500 mg twice daily → up to 2000-2500 mg/day
• Benefits: Weight neutral, no hypoglycemia, cheap, cardioprotective
• Side effects: GI upset (nausea, diarrhea) - take with food; rare lactic acidosis
• Contraindications: eGFR <30, iodinated contrast dye procedures, liver failure, alcohol excess

---

Step 2: Add a Second Agent (if HbA1c not at target on metformin)

---

Step 3: Triple Combination Therapy

• Add a third agent if dual therapy fails to achieve target
• Common combos: Metformin + SGLT2i + GLP-1RA (best cardiorenal protection)

Step 4: Insulin in T2DM

• Oral agents fail to maintain HbA1c target
• HbA1c ≥9% with symptoms at diagnosis
• DKA or HHS
• Critically ill/hospitalized patients
• Pregnancy
• Chronic kidney disease (many oral agents contraindicated)

• Begin with basal insulin (e.g., Glargine 10 units/night) + continue metformin
• Titrate by 2 units every 3 days to reach fasting glucose 80-130 mg/dL
• If still uncontrolled, add premeal rapid-acting insulin (basal-plus or basal-bolus)

---

C. MANAGEMENT OF COMORBIDITIES

Blood Pressure Control

• Target: <130/80 mmHg
• First-line: ACE inhibitor or ARB (nephroprotective - mandatory if proteinuria present)
• Second-line: Calcium channel blockers, diuretics

Dyslipidemia Management

• All T2DM patients >40 years: Statin therapy (moderate to high intensity)
• LDL target: <70 mg/dL in high CV risk; <55 mg/dL in very high risk
• Add ezetimibe or PCSK9 inhibitor if statin alone insufficient
• Fenofibrate for hypertriglyceridemia

Antiplatelet Therapy

• Aspirin 75-100 mg/day: Secondary prevention in established CVD
• Primary prevention: only if high CV risk (benefit outweighs GI bleed risk)

---

D. MANAGEMENT OF ACUTE COMPLICATIONS

1. Hypoglycemia (Blood glucose <70 mg/dL)

• Mild-Moderate: 15-20g fast-acting glucose orally (juice, glucose tablets); recheck in 15 min ("15-15 rule")
• Severe (unconscious): IV Dextrose 25-50 mL of 50% dextrose, OR IM/SC Glucagon 1 mg
• Identify and treat the cause (missed meal, excess insulin, exercise)

2. Diabetic Ketoacidosis (DKA) - Type 1 Emergency

• IV Fluids: 0.9% Normal saline - 1L in first hour, then guided by deficit
• Insulin: Regular insulin IV infusion 0.1 units/kg/hr (after K+ >3.5 mEq/L confirmed)
• Potassium replacement: Add K+ to fluids once urine output confirmed (DKA depletes K+)
• Bicarbonate: Only if pH <6.9
• Monitoring: Glucose hourly, electrolytes 2-4 hourly; switch to SC insulin when glucose <200 mg/dL + anion gap closed

3. Hyperosmolar Hyperglycemic State (HHS) - Type 2 Emergency

• Large volume IV fluid replacement (deficit often 8-12L)
• Cautious insulin infusion at lower doses
• Correct electrolytes; treat underlying precipitant

---

E. MANAGEMENT OF CHRONIC COMPLICATIONS

---

F. MONITORING SCHEDULE

---

G. PREVENTION OF T2DM (Primary Prevention)

• Lifestyle intervention (7% weight loss + 150 min/week exercise): reduces DM risk by 60%
• Metformin: reduces risk by ~25% (used in high-risk prediabetes patients)
• Liraglutide 3 mg/day: reduces incident DM by ~20% in obese prediabetes
• Screen all adults >35 years with risk factors every 3 years

---

---

Complications of Diabetes Mellitus

---

CLASSIFICATION AT A GLANCE

COMPLICATIONS OF DM
├── ACUTE
│   ├── Diabetic Ketoacidosis (DKA)
│   ├── Hyperosmolar Hyperglycemic State (HHS)
│   └── Hypoglycemia
└── CHRONIC
    ├── MICROVASCULAR
    │   ├── Diabetic Retinopathy
    │   ├── Diabetic Nephropathy
    │   └── Diabetic Neuropathy
    ├── MACROVASCULAR
    │   ├── Coronary Artery Disease
    │   ├── Cerebrovascular Disease
    │   └── Peripheral Arterial Disease
    └── OTHER
        ├── Diabetic Foot
        ├── Infections
        └── Skin complications

---

PATHOGENESIS OF CHRONIC COMPLICATIONS

1. AGE formation - Advanced Glycation End Products bind to RAGE receptors on endothelium and macrophages → vascular injury, basement membrane damage
2. Polyol pathway activation - Glucose converted to sorbitol by aldose reductase → osmotic damage to nerves and lens
3. Protein Kinase C (PKC) activation - Alters vascular permeability, blood flow, endothelial function
4. Oxidative stress - Reactive oxygen species damage endothelium and mitochondria

• Chronic hyperglycemia also causes diffuse basement membrane thickening in capillaries of skin, retina, glomeruli, and peripheral nerves

---

ACUTE COMPLICATIONS

1. Diabetic Ketoacidosis (DKA) - Mainly Type 1 DM

• Absolute insulin deficiency → uncontrolled lipolysis → ketone body production → metabolic acidosis
• Triad: Hyperglycemia (>250 mg/dL) + Ketonemia + High anion gap metabolic acidosis (pH <7.3)
• Symptoms: Polyuria, polydipsia, vomiting, abdominal pain, Kussmaul breathing, fruity breath, altered consciousness
• Precipitants: Infection, missed insulin doses, surgery, MI, stress
• Mortality: ~1-5% if untreated

2. Hyperosmolar Hyperglycemic State (HHS) - Mainly Type 2 DM

• Severe hyperglycemia (>600 mg/dL) without significant ketosis
• Profound dehydration (8-12 L fluid deficit), serum osmolality >320 mOsm/kg
• Symptoms: Extreme thirst, weakness, altered consciousness, focal neurological signs, seizures
• Mortality: 5-20% (higher than DKA)

3. Hypoglycemia (Blood glucose <70 mg/dL)

• Causes: Excess insulin, missed meal, excessive exercise, alcohol, drug interactions
• Neurogenic symptoms: Sweating, palpitations, tremor, anxiety (from catecholamine release)
• Neuroglycopenic symptoms: Confusion, dizziness, blurred vision, seizures, coma
• Hypoglycemia unawareness: Long-standing DM patients lose warning symptoms due to autonomic neuropathy
• Can cause permanent neurological damage if prolonged

---

CHRONIC COMPLICATIONS

---

MICROVASCULAR COMPLICATIONS

1. Diabetic Retinopathy

• Most common cause of new blindness in adults aged 20-74 years
• 60-80% of diabetics develop some form of retinopathy
• Risk factors: Duration of DM, poor glycemic control, hypertension, nephropathy, dyslipidemia

• Other ocular complications: Cataracts (earlier onset), Glaucoma (increased intraocular pressure)
• Fundamental lesion: VEGF-driven neovascularization in response to retinal hypoxia

---

2. Diabetic Nephropathy

• Leading cause of End-Stage Renal Disease (ESRD) in the United States
• Affects 20-40% of all diabetic patients
• Renal failure is the second most common cause of death in diabetes (after MI)

• Capillary basement membrane thickening (earliest)
• Diffuse mesangial sclerosis (most common)
• Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) - pathognomonic of diabetic nephropathy
• Arteriolosclerosis of afferent AND efferent arterioles (efferent sclerosis = specific to DM)
• Pyelonephritis and papillary necrosis (more common in diabetics)

---

3. Diabetic Neuropathy

• Affects ~50% of individuals with long-standing DM (up to 80% after 15 years)
• Both myelinated and unmyelinated nerve fibers are affected

A. Distal Symmetric Polyneuropathy (DSPN) - Most Common

• Stocking-and-glove pattern of sensory loss
• Symptoms: Burning, tingling, numbness starting in toes/feet → hands
• Loss of vibration sense, proprioception, pain sensation
• Reduced/absent ankle reflexes
• Leads to: foot ulcers, falls, Charcot joint

B. Autonomic Neuropathy

• Cardiovascular: Resting tachycardia, postural hypotension, silent myocardial ischemia, sudden cardiac death
• GI: Gastroparesis (delayed gastric emptying → nausea, vomiting, erratic glucose), diabetic diarrhea, constipation
• Genitourinary: Neurogenic bladder (incomplete emptying, UTI), erectile dysfunction (in ~50% of male diabetics)
• Sweating: Anhidrosis of feet (dry, cracked skin → infection), gustatory sweating

C. Mononeuropathy

• Sudden onset palsy of a single nerve
• Cranial nerve palsies: CN III (oculomotor - ptosis + ophthalmoplegia), CN VI, CN VII
• Peripheral: Carpal tunnel syndrome, foot drop (peroneal), wrist drop (radial)

D. Diabetic Amyotrophy (Proximal Motor Neuropathy)

• Severe pain + weakness in hip/thigh muscles (femoral nerve)
• Usually unilateral, in elderly T2DM patients
• Partially reversible with glycemic control

E. Autonomic Cardiovascular Neuropathy

• Prolonged QT interval → increased risk of sudden death
• Fixed heart rate ("cardiac denervation") - does not vary with respiration

---

MACROVASCULAR COMPLICATIONS

4. Coronary Artery Disease (CAD)

• Most common cause of death in diabetes
• 2-4x greater incidence of CAD vs. non-diabetics
• T2DM patients without prior MI have similar CV risk as non-diabetics WITH prior MI
• Silent ischemia very common (no chest pain due to autonomic neuropathy)
• More frequently involves multiple vessels
• CABG outcomes better than PCI for diabetic patients with multi-vessel disease
• Diabetic Cardiomyopathy: Left ventricular dysfunction without CAD or hypertension; pathogenesis unclear

5. Cerebrovascular Disease (Stroke)

• 4x higher risk of cerebrovascular accidents
• Both ischemic stroke and TIA more common
• Lacunar infarcts (small vessel disease) especially prevalent

6. Peripheral Arterial Disease (PAD)

• Accelerated atherosclerosis of lower limb arteries
• Symptoms: Intermittent claudication, rest pain, cold extremities, absent pedal pulses
• Gangrene of lower extremities is 100x more common in diabetics vs. general population
• Major driver of non-traumatic lower limb amputation

---

OTHER COMPLICATIONS

7. Diabetic Foot

• Result of combined neuropathy + ischemia + infection
• Neuropathic foot: Warm, well-perfused, insensate, bounding pulses; plantar ulcers; Charcot joint
• Ischemic foot: Cold, painful, poor perfusion; absent pulses; necrosis at tips of toes
• Charcot Neuroarthropathy: Painless destructive arthropathy of foot/ankle joints due to loss of protective pain sensation → deformity ("rocker-bottom foot")
• Minor trauma → ulcer → secondary infection → osteomyelitis → gangrene → amputation

8. Increased Susceptibility to Infections

• Impaired neutrophil chemotaxis, adherence, phagocytosis, microbicidal activity
• Reduced cytokine production by macrophages
• Vascular compromise impairs immune cell delivery to infection sites
• Common infections: Skin infections, UTI, candidiasis, TB, pneumonia, pyelonephritis
• Specific infections in diabetics:
  • Rhinocerebral mucormycosis (rapidly fatal fungal infection)
  • Malignant otitis externa (Pseudomonas)
  • Emphysematous cholecystitis
  • Necrotizing fasciitis
  • Fournier's gangrene

9. Skin Complications

• Diabetic dermopathy (shin spots): Most common; brown atrophic lesions on pretibial surface; correlates with retinopathy, nephropathy, neuropathy
• Acanthosis nigricans (insulin resistance marker)
• Necrobiosis lipoidica diabeticorum: Yellow-brown atrophic plaques on shins
• Diabetic bullae (bullosis diabeticorum)

10. Hypertension & Dyslipidemia (Cardiovascular Risk Amplifiers)

• Hypertension present in ~75% of T2DM patients
• Diabetic dyslipidemia: High TG + High LDL + Low HDL → accelerated atherosclerosis
• Insulin resistance drives dyslipidemia through increased VLDL production

11. Heart Failure

• Twice as common in diabetics vs. non-diabetics
• Can present as HFpEF, HFmEF, or HFrEF
• Related to diabetes duration, hypertension, CAD, and direct metabolic damage

---

SUMMARY TABLE

---