Clinical meaning
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease characterized by insulin resistance and relative insulin deficiency. The pathophysiology involves the 'ominous octet' (DeFronzo): (1) Decreased insulin secretion (beta-cell dysfunction — progressive loss of beta-cell mass and function), (2) Increased glucagon secretion (alpha-cell dysregulation), (3) Increased hepatic glucose production (hepatic insulin resistance — failure to suppress gluconeogenesis and glycogenolysis), (4) Decreased peripheral glucose uptake (skeletal muscle insulin resistance — impaired GLUT4 translocation), (5) Increased lipolysis (adipose insulin resistance — elevated free fatty acids cause lipotoxicity), (6) Decreased incretin effect (reduced GLP-1 secretion and action), (7) Increased renal glucose reabsorption (upregulated SGLT2 in proximal tubule), (8) Neurotransmitter dysfunction (hypothalamic appetite dysregulation). Diagnostic criteria (ADA): Fasting plasma glucose (FPG) ≥126 mg/dL (fasting defined as no caloric intake for ≥8 hours), 2-hour plasma glucose ≥200 mg/dL during oral glucose tolerance test (OGTT — 75g glucose load), HbA1c ≥6.5% (reflects average glucose over 2-3 months; affected by hemoglobin variants, anemia, and red cell turnover), or random plasma glucose ≥200 mg/dL with classic hyperglycemic symptoms (polyuria, polydipsia, weight loss). In the ABSENCE of unequivocal...