Diabetes Mellitus (Type 1 & 2)

“Diabetes” is a shared endpoint — inappropriately high blood glucose — reached by two very different roads. Type 1 is an autoimmune disease: the immune system destroys the pancreatic β-cells, producing an absolute insulin deficiency — insulin is absent or extremely low. The attack leaves fingerprints the lab can find: islet autoantibodies (GAD65, IA-2, ZnT8, insulin autoantibody), and a low C-peptide confirms how little β-cell function remains when the diagnosis is unclear. It accounts for roughly 5–10% of all diabetes, clusters with other autoimmune diseases, and can announce itself abruptly — in children, 15–70% of new type 1 diagnoses present in DKA.

Type 2 — about 90% of all diabetes, with roughly 1 in 11 adults worldwide affected — is a nonautoimmune, progressive story. It begins with insulin resistance, commonly from obesity and aging: tissues stop responding, so the pancreas compensates with hyperinsulinemia and glucose stays normal — for a while. Over years the overworked β-cells lose secretory capacity, insulin production falls behind demand, and a relative (not absolute) insulin deficit lets glucose climb. The distinction drives everything downstream: type 1 requires insulin from day one; type 2 starts with lifestyle and oral agents and may need insulin later.

Type 1 itself is now staged (ADA 2026): stage 1 is multiple islet autoantibodies with normal glucose, stage 2 adds dysglycemia — both presymptomatic — and stage 3 is overt hyperglycemia meeting standard diagnostic criteria. The disease is underway years before the first symptom.

The classic symptoms are pure renal physiology. The nephron reabsorbs filtered glucose through transporters with a finite capacity; sustained hyperglycemia saturates them, and the excess spills into the urine (glycosuria). Glucose in the tubule is osmotically active — it drags water with it — producing osmotic diuresis and the first P, polyuria. The resulting dehydration (watch for poor skin turgor) drives the second P, polydipsia. Symptoms typically appear once serum glucose runs above roughly 250 mg/dL, though a glucose above 180 mg/dL is already considered hyperglycemic.

Meanwhile the cells are starving in the middle of plenty: without effective insulin they cannot take glucose in, so despite a high blood sugar the body behaves as if unfed — unintentional weight loss and fatigue. This is why a newly diagnosed type 1 patient is classically thin, thirsty, exhausted, and urinating constantly.

Pre-breakfast hyperglycemia has two textbook explanations, and the exam loves the distinction. The dawn phenomenon — the more common of the two — is a nocturnal rise in glycogenolysis and gluconeogenesis, amplified by growth hormone’s insulin-antagonist effect and by exogenous insulin waning overnight. Glucose drifts up through the early morning without any preceding low.

The Somogyi phenomenon is the proposed rebound: nocturnal hypoglycemia triggers counterregulatory hormones (adrenaline, corticosteroids, growth hormone, glucagon) that overshoot into morning hyperglycemia. The differentiator is the overnight number: check glucose around 2–3 AM (or use CGM, the gold standard) — a low overnight reading points to Somogyi; a normal or steadily rising overnight glucose without hypoglycemia is the dawn phenomenon. Worth knowing: recent studies dispute the Somogyi mechanism — nocturnal hypoglycemia is usually followed by morning hypoglycemia, not hyperglycemia — but the classic distinction is still taught and still tested.

Chronic hyperglycemia drives nonenzymatic glycation — glucose chemically bonding to proteins and lipids it was never meant to touch. In the smallest vessels this produces the microvascular triad: retinopathy (12,000–24,000 new cases of blindness annually in the US), nephropathy (diabetes is the leading cause of end-stage renal disease in the US), and neuropathy — both peripheral, setting up the diabetic foot, and autonomic.

In the large vessels, diabetes accelerates atherosclerosis into macrovascular disease: coronary artery disease, peripheral artery disease, and cerebrovascular disease. Approximately two-thirds of people with diabetes die of myocardial infarction or stroke — and a fasting glucose above just 100 mg/dL already contributes to ASCVD risk. This is why modern drug selection asks about the heart and kidneys first, and why the diabetes page connects to the CAD and CKD pages.

Acute stress works on the same dial in fast-forward: illness, trauma, and surgery raise glucose through catecholamines, cortisol, and increased hepatic glucose output. That surge is the mechanistic “why” behind every sick-day rule — infection raises insulin demand exactly when the patient feels least like eating or dosing — and stress hyperglycemia in a patient without known diabetes should prompt an A1C.