Pathophysiology_of_Type_2_Diabetejjjjjjjjjjjjjkks.pptx

General basics

1. Pathophysiology of Type 2 Diabetes Mellitus An Overview of Mechanisms and Clinical Implications

2. Introduction • Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, progressive pancreatic β-cell dysfunction, and hyperglycemia. • It accounts for 90–95% of all diabetes cases worldwide. • Strongly associated with obesity, sedentary lifestyle, and genetic predisposition.

3. Normal Glucose Homeostasis • Insulin, produced by pancreatic β-cells, facilitates glucose uptake into muscle and fat cells. • The liver maintains glucose balance by glycogen synthesis and gluconeogenesis. • A feedback mechanism between glucose levels and insulin secretion maintains euglycemia.

4. Pathophysiological Mechanisms • Insulin resistance in skeletal muscle and adipose tissue. • Increased hepatic glucose production. • Impaired pancreatic β-cell function and insulin secretion. • Altered incretin effect (GLP-1 and GIP deficiency). • Increased renal glucose reabsorption.

5. Insulin Resistance • Muscle: Decreased glucose uptake and utilization. • Liver: Failure to suppress gluconeogenesis. • Adipose tissue: Increased lipolysis leading to elevated free fatty acids. • Results in chronic hyperglycemia and compensatory hyperinsulinemia.

6. β-Cell Dysfunction • Chronic exposure to high glucose (glucotoxicity) and fatty acids (lipotoxicity) impairs β-cell function. • Genetic predisposition influences β-cell decline. • Progressive loss of insulin secretory capacity over time.

7. Role of Adipose Tissue • Adipokines such as TNF-α, IL-6, and resistin promote insulin resistance. • Decreased adiponectin reduces insulin sensitivity. • Ectopic fat deposition in liver and muscle aggravates metabolic dysfunction.

8. Incretin Effect • Incretin hormones (GLP-1 and GIP) enhance insulin secretion post-meal. • In T2DM, the incretin effect is blunted due to reduced GLP-1 secretion and GIP resistance. • Target for therapy: GLP-1 receptor agonists and DPP-4 inhibitors.

9. Summary of Pathophysiology • Central triad: Insulin resistance, β-cell dysfunction, and increased hepatic glucose output. • Contributing factors: Incretin deficiency, lipotoxicity, and inflammation. • Leads to persistent hyperglycemia and long-term complications.

10. Clinical Implications • Understanding pathophysiology guides pharmacologic interventions. • Insulin sensitizers (metformin, TZDs) target insulin resistance. • Secretagogues and incretin-based therapies enhance insulin secretion. • Combination therapy often required to address multiple defects.

11. Conclusion • Type 2 diabetes results from complex interactions between genetic, metabolic, and environmental factors. • Early detection and intervention can prevent β-cell exhaustion and complications. • Lifestyle modification remains the cornerstone of prevention and management.