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.
- Metformin: First-line (reduces hepatic gluconeogenesis).
- Monitoring:
- HbA1c: Goal <7.0% (individualized).
- Blood pressure: <130/80 mmHg.
- Lipids: LDL-C <70 mg/dL (high CV risk).