Diabetes Mellitus: Pathophysiology & Management

Diabetes Mellitus

Diagnostic Criteria (WHO 2023)

• Fasting plasma glucose ÔëÑ7.0 mmol/L
• 2-hour OGTT ÔëÑ11.1 mmol/L
• HbA1c ÔëÑ48 mmol/mol (6.5%)
• Random glucose ÔëÑ11.1 mmol/L with symptoms

(Asymptomatic: repeat on different day to confirm)

Type 1 vs Type 2 DM

| Feature | T1DM | T2DM |

|---------|------|------|

| Mechanism | Autoimmune ╬▓-cell destruction | Insulin resistance + progressive ╬▓-cell failure |

| Age of onset | <30 (typically) | >40 (increasingly younger) |

| Onset | Acute, ketosis-prone | Gradual, often incidental |

| Antibodies | GAD, IA-2, ZnT8 | Negative |

| Treatment | Insulin mandatory | Lifestyle → metformin → escalate |

T2DM Pharmacological Ladder

1. Metformin (AMPK activation → Ôåô hepatic glucose output; GI side-effects; stop if eGFR <30)
2. + SGLT2 inhibitor (if CVD/HF/CKD) or GLP-1 RA (if obesity) for organ protection
3. + DPP-4 inhibitor or sulfonylurea
4. Insulin (basal ┬▒ bolus)

Diabetic Ketoacidosis (DKA)

• Criteria: glucose >11 mmol/L (or known DM), pH <7.3 or bicarb <15, ketonaemia ÔëÑ3 mmol/L
• Mechanism: insulin deficiency → unrestrained lipolysis → FFA → hepatic ketogenesis (acetoacetate, ╬▓-hydroxybutyrate)
• Treatment: fixed rate IV insulin (0.1 units/kg/hr), IV fluid (0.9% NaCl), K+ replacement (never start insulin if K+ <3.5)

Chronic Complications

• Microvascular: retinopathy, nephropathy, peripheral neuropathy
• Macrovascular: MI, stroke, PVD (2–4├ù increased risk)
• Diabetic nephropathy: microalbuminuria → proteinuria → CKD; treat with ACEi/ARB + SGLT2i