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 hyperglycemia, diagnosis requires TWO abnormal results (either two different tests or the same test on two occasions). Prediabetes: FPG 100-125 (impaired fasting glucose), 2-hr OGTT 140-199 (impaired glucose tolerance), or HbA1c 5.7-6.4%.