PATHOPHYSIOLOGY • TOPIC 2 / 100 • Endocrine & Metabolic
Type 2 Diabetes Mellitus
Mechanistic algorithm
Genetic susceptibility + visceral adiposity/inactivity → insulin resistance in muscle/liver/adipose tissue → compensatory hyperinsulinaemia → β-cell stress and dysfunction → relative insulin deficiency → fasting + post-prandial hyperglycaemia → glucotoxicity/lipotoxicity → progressive β-cell failure
Insulin resistance reduces skeletal-muscle glucose uptake, fails to suppress hepatic gluconeogenesis and increases adipose lipolysis, delivering free fatty acids to liver and muscle.
β-cells initially increase insulin secretion, but chronic nutrient excess, islet amyloid, oxidative/ER stress and inflammatory signalling progressively impair β-cell mass and function.
Incretin effect is reduced, glucagon secretion is inappropriately high, and renal glucose reabsorption remains increased; these defects sustain hyperglycaemia.
Long-term AGE formation, oxidative stress, PKC activation and endothelial dysfunction drive microvascular and macrovascular complications.
Educational learning module. The mechanism is written to emphasise clinically meaningful physiology and may be read alongside a standard textbook for deeper molecular detail.