Diabetes mellitus type 2 – etiology, pathogenesis, and clinical manifestations.
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by insulin resistance and relative insulin deficiency, resulting in hyperglycemia.
- Most common type of diabetes (90–95% of cases).
Etiology (Causes)
- 1 Genetic predisposition
- Stronger genetic component than type 1 diabetes.
- Polygenic inheritance; multiple susceptibility genes (e.g., TCF7L2).
- 2 Environmental and lifestyle factors
- Obesity (especially central/visceral obesity): most important modifiable risk factor.
- Sedentary lifestyle.
- High- calorie diet.
- Aging.
Pathogenesis
- 1 Insulin resistance
- Peripheral tissues (muscle, adipose tissue, liver) respond poorly to insulin.
- Contributing mechanisms:
- Downregulation or defects in insulin receptors or post-receptor signaling.
- Adipokine imbalance (e.g., decreased adiponectin, increased resistin, TNF- α).
- 2 β- cell dysfunction (relative insulin deficiency)
- Initially, β- cells compensate by hypersecretion of insulin.
- Over time, β-cell exhaustion and apoptosis occur.
- Amyloid deposition in islets may contribute to β- cell dysfunction.
- 3 Hepatic glucose overproduction
- Increased gluconeogenesis despite hyperglycemia.
- 4 Lipotoxicity and glucotoxicity
- Chronic high levels of fatty acids and glucose further impair β-cell function and insulin sensitivity.