Diabetes Pathophysiology, Epidemiology, and Prevention
Pathophysiology
Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells, producing absolute insulin deficiency; islet autoantibodies (GAD65, IA-2, ZnT8) may appear years before symptoms, and a substantial minority present in diabetic ketoacidosis. Type 2 diabetes reflects insulin resistance plus progressive beta-cell failure, worsened by an incretin defect, excess glucagon, and increased hepatic glucose output. Linking mechanism to medication class is a favorite exam move: metformin suppresses hepatic glucose production, GLP-1 receptor agonists restore the incretin effect, SGLT2 inhibitors cause glycosuria.
Epidemiology
Prevalence rises with age, obesity, and certain populations ( Indigenous, Hispanic, African American, Asian American, Pacific Islander), and many people have prediabetes or undiagnosed disease for years. Gestational diabetes is typically screened at 24-28 weeks with a 75-g 2-hour OGTT (one-step) or a two-step 50-g screen followed by a 100-g 3-hour test.
Diagnosis and prevention
Diagnostic thresholds: A1c ≥6.5%, fasting plasma glucose ≥126 mg/dL (8-hour fast), 2-hour OGTT ≥200 mg/dL, or random glucose ≥200 mg/dL with classic symptoms. Prediabetes: A1c 5.7-6.4%, impaired fasting glucose 100-125 mg/dL, impaired glucose tolerance 140-199 mg/dL. The Diabetes Prevention Program showed intensive lifestyle (7% weight loss, 150 min/week activity) cut progression to type 2 diabetes by 58%, versus 31% with metformin.
Traps
A1c is unreliable in hemoglobinopathies, pregnancy, hemolysis, recent transfusion, and dialysis; use plasma glucose instead. Iron deficiency can falsely raise A1c. A single normal glucose does not exclude diabetes in a symptomatic patient, and screening requires confirmation with a second test unless the diagnosis is unequivocal.