Epidemiology, Pathogenesis, Risk Factors, and Clinical Progression of Type 2 Diabetes

Pathogenesis of Type 2 Diabetes: Cellular Mechanisms, Insulin Resistance, and Genetic Predisposition

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction. Its prevalence continues to rise globally, creating substantial healthcare burdens.

Cellular Mechanisms

At the cellular level, insulin resistance emerges due to defects in insulin signaling pathways, leading to impaired glucose uptake. Dysfunction in β-cells results in inadequate insulin secretion, worsening hyperglycemia.

Insulin Resistance

Insulin resistance is primarily driven by excess adiposity and inflammatory responses, contributing to reduced glucose metabolism. Key molecular players include IRS-1, PI3K, and GLUT-4.

Genetic Predisposition

Several genetic variants, including TCF7L2 and KCNJ11, have been associated with increased susceptibility to T2DM, affecting β-cell function and insulin sensitivity.

Risk Factors and Economic Impact

• Obesity and sedentary lifestyle
• Genetic predisposition
• Dietary factors
• Economic burden on healthcare systems due to long-term management and complications

Clinical Progression

The disease progresses through stages ranging from insulin resistance to β-cell failure, eventually leading to chronic hyperglycemia and associated complications such as nephropathy, retinopathy, and cardiovascular disease.