Definition: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, relative insulin deficiency, and hyperglycemia.

• Pathophysiology:
  • Insulin resistance: Impaired glucose uptake in peripheral tissues (muscle, liver, adipose).
  • Beta-cell dysfunction: Progressive decline in insulin secretion due to beta-cell exhaustion.
  • Incretin deficiency: Reduced GLP-1 and GIP secretion, impairing glucose-dependent insulin release.
• Diagnostic Criteria (ADA 2026):
  • Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L).
  • HbA1c ≥ 6.5% (48 mmol/mol).
  • 2-hour OGTT ≥ 200 mg/dL (11.1 mmol/L).
  • Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with symptoms.
• Complications:
  • Microvascular: Retinopathy, nephropathy, neuropathy.
  • Macrovascular: CVD, PAD, stroke.
  • Rationale: Chronic hyperglycemia and dyslipidemia drive both.
• Management (ADA 2026):
  • Lifestyle: Diet, exercise, weight loss (5–10% body weight).
  • Pharmacotherapy:
    • Metformin: First-line (reduces hepatic gluconeogenesis).
    • GLP-1RAs: Improve beta-cell function, reduce CV risk.
    • SGLT-2 inhibitors: Reduce CV risk, HF hospitalization.
    • Rationale: Targets both glycemia and CV risk factors.
• Monitoring:
  • HbA1c: Goal <7.0% (individualized).
  • Blood pressure: <130/80 mmHg.
  • Lipids: LDL-C <70 mg/dL (high CV risk).