Diabetes Mellitus and Glucose Metabolism
Diagnosis and classification
Diabetes is defined by plasma glucose or A1c criteria: fasting plasma glucose ≥126 mg/dL after an ≥8-hour fast; 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test; A1c ≥6.5%; or random plasma glucose ≥200 mg/dL with classic symptoms or hyperglycemic crisis. Prediabetes ranges are fasting 100–125 mg/dL, 2-hour 140–199 mg/dL, and A1c 5.7–6.4%. In an asymptomatic patient, confirm an abnormal result with a second test on a different day unless the diagnosis is unequivocal. A1c reflects 2–3 months of glycemia but is unreliable in hemoglobinopathies, hemolysis, recent transfusion, iron deficiency, pregnancy, and advanced CKD; use plasma glucose when results are discordant.
Management and complications
Type 1 diabetes requires insulin from diagnosis. Type 2 diabetes begins with lifestyle plus metformin unless contraindicated or the patient is catabolic. Metformin is contraindicated at eGFR <30 mL/min/1.73 m² and should not be initiated at eGFR 30–45. SGLT2 inhibitors reduce heart failure and CKD progression but can cause euglycemic DKA and genital mycotic infections. GLP-1 receptor agonists promote weight loss but cause gastrointestinal effects and are avoided with medullary thyroid carcinoma or MEN2. Sulfonylureas and insulin cause hypoglycemia. Screen for retinopathy, nephropathy, neuropathy, and foot disease. In DKA, check potassium before insulin; total-body potassium is depleted even when serum potassium is normal or high. HHS has higher glucose and osmolality with less ketosis.
Trap and worked example
A 48-year-old with polyuria, polydipsia, and random glucose 284 mg/dL has diabetes; symptoms make a confirmatory test unnecessary. A screening A1c of 6.1% in a patient with sickle cell trait should not be used alone; obtain fasting glucose or an OGTT. Rule of thumb: treat the patient, not the A1c, when anemia, CKD, or hemoglobin variants distort results.