Type 2 Diabetes Mellitus: Pathophysiology, Complications and Drug Cascade (CMS + NEET PG)

Pathophysiology

Type 2 DM involves insulin resistance in peripheral tissues, progressive beta-cell dysfunction, increased hepatic glucose output, and incretin deficiency.

Diagnosis Criteria

• Fasting glucose >= 126 mg/dL
• 2h post-glucose >= 200 mg/dL (OGTT)
• HbA1c >= 6.5%
• Random glucose >= 200 mg/dL with symptoms

Stepwise Drug Cascade

1. Metformin (1st line) — reduces hepatic gluconeogenesis
2. Metformin + SGLT2i or GLP-1 RA (2nd line) — add based on CV/renal risk
3. Metformin + SGLT2i + GLP-1 RA (3rd line)
4. Add insulin if HbA1c remains >7.5%

Complications

Microvascular: Retinopathy, Nephropathy, Neuropathy. Macrovascular: MI, Stroke, PVD.

Special Situations

Pregnancy: Insulin only (oral agents contraindicated). Surgery: Switch to insulin peri-operatively.