Diabetes Mellitus - 10 Mark Answer

Definition

Classification (ADA, 1997)

• Accounts for 5-10% of all diabetes cases
• Caused by cellular-mediated autoimmune destruction of the beta (β) cells of the pancreas, leading to absolute insulin deficiency
• Patients are prone to diabetic ketoacidosis (DKA)
• Sub-types: (A) Immune-mediated, (B) Idiopathic

• Most common type - accounts for >90% of all cases
• Characterized by insulin resistance followed by reduced insulin secretion from β cells that are unable to compensate for increased insulin requirements
• Usually associated with obesity; patients are rarely ketosis-prone

• Genetic defects of β-cell function (e.g., MODY - Maturity Onset Diabetes of the Young)
• Genetic defects in insulin action
• Diseases of the exocrine pancreas (e.g., pancreatitis, cystic fibrosis) - now called Type 3c diabetes
• Endocrinopathies (Cushing syndrome, acromegaly, pheochromocytoma)
• Drug/chemical-induced (corticosteroids, antiretrovirals, atypical antipsychotics)

• Glucose intolerance with onset or first recognition during pregnancy
• Occurs in approximately 6-8% of pregnancies in the US
• About 50% of women with GDM develop T2DM within 5-10 years

Pathophysiology

• Autoimmune T-cell-mediated destruction of β cells in the islets of Langerhans
• Genetic predisposition (HLA-DR3, HLA-DR4 associations)
• Results in absolute insulin deficiency
• Without insulin: increased gluconeogenesis, glycogenolysis, lipolysis → hyperglycemia and ketoacidosis

• Two main defects: peripheral insulin resistance (especially in muscle and fat) + impaired insulin secretion
• Insulin resistance → compensatory hyperinsulinemia → β-cell exhaustion → relative insulin deficiency
• Associated with obesity, physical inactivity, and genetic factors

Diagnostic Criteria (ADA)

• Washington Manual of Medical Therapeutics

Clinical Features

• Polyuria - osmotic diuresis from glycosuria
• Polydipsia - compensatory to fluid loss
• Polyphagia - tissue starvation despite high blood glucose

Complications

Acute Complications

1. Diabetic Ketoacidosis (DKA) - mainly in T1DM; due to absolute insulin deficiency, leading to excessive ketone body production; presents with nausea, vomiting, abdominal pain, Kussmaul breathing, fruity breath, altered consciousness
2. Hyperglycemic Hyperosmolar State (HHS) - mainly in T2DM; extreme hyperglycemia without significant ketosis; severe dehydration
3. Hypoglycemia - due to excess insulin or oral hypoglycemics; presents with sweating, tremors, confusion, seizures

Chronic Complications

• Diabetic Retinopathy - leading cause of blindness in working-age adults; background (non-proliferative) → proliferative retinopathy
• Diabetic Nephropathy - leading cause of end-stage renal disease (ESRD); hallmark: microalbuminuria → proteinuria → declining GFR
• Diabetic Neuropathy - most common complication; peripheral (glove-and-stocking sensory loss), autonomic (gastroparesis, orthostatic hypotension), and mononeuropathy

• Coronary artery disease (CAD) - diabetes is considered a "cardiac risk equivalent"
• Stroke
• Peripheral arterial disease (PAD) - risk of foot ulcers and amputation

Treatment

Non-Pharmacological

• Lifestyle modification: balanced diet, weight reduction, regular aerobic exercise (150 min/week)
• Medical nutrition therapy (MNT)
• Patient education and self-monitoring of blood glucose (SMBG)

Pharmacological - Type 1 DM

• Insulin therapy is mandatory (basal-bolus regimen or continuous subcutaneous insulin infusion)
• Common regimens: long-acting insulin (glargine/detemir) + short-acting (lispro/aspart) with meals

Pharmacological - Type 2 DM

• Metformin - first-line drug for most T2DM patients; inhibits hepatic gluconeogenesis; reduces insulin resistance; weight neutral; inexpensive

• Sulfonylureas (glipizide, glyburide) - stimulate insulin secretion
• GLP-1 receptor agonists (semaglutide, liraglutide) - weight loss benefit, cardiovascular benefit
• SGLT-2 inhibitors (empagliflozin, dapagliflozin) - promote glycosuria; renal and cardiovascular protective
• DPP-4 inhibitors (sitagliptin) - weight neutral
• Insulin - when oral agents fail to achieve glycemic targets

Glycemic Targets

• HbA1c: <7% (standard goal); individualized based on age, comorbidities, risk of hypoglycemia
• Fasting BG: 80-130 mg/dL; Postprandial BG: <180 mg/dL

Management of Comorbidities

• Blood pressure: target <140/90 mmHg (ACE inhibitor or ARB first-line, also protective for nephropathy)
• Lipids: high-intensity statin therapy for patients aged 40-75
• Aspirin: for cardiovascular disease prevention in diabetics with CVD

Prevention

• T2DM can be prevented or delayed by lifestyle modification (weight loss of 5-7%, 150 min/week exercise)
• Metformin may be used for high-risk individuals (BMI ≥35, younger patients with progressive hyperglycemia)
• Regular screening every 3 years for high-risk individuals (obesity, family history, GDM history)

Summary Table