TOPIC
MECHANISM
FEATURES
CLUE · TREATMENT
T-cell (type IV) destruction of β cells; HLA-DR3/DR4; anti-GAD65, anti-insulin, IA-2, ZnT8 antibodies
Children/young adults; abrupt polyuria, polydipsia, polyphagia, weight loss; insulitis
↓ C-peptide · insulin required
Insulin resistance (visceral obesity, inactivity) + progressive β-cell dysfunction; strong family link
Adults; gradual or asymptomatic; acanthosis nigricans; islet amyloid (amylin) deposits
Metformin first · normal/↑ C-peptide early
Thresholds for hyperglycemia
Fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, 2-h OGTT ≥ 200, or random ≥ 200 with symptoms
HbA1c reflects ~3 months
No insulin + ↑ glucagon, cortisol, catecholamines → lipolysis → FFAs → hepatic ketones (acetoacetate, β-hydroxybutyrate)
High anion gap acidosis, Kussmaul breathing, fruity breath, vomiting, abdominal pain, dehydration; trigger: infection, missed insulin
Fluids + IV insulin + K⁺; add dextrose as glucose falls
Insulin lack and acidosis shift K⁺ out of cells; osmotic diuresis wastes it
Serum K⁺ normal or ↑ but total body K⁺ depleted
Insulin drives K⁺ in → hypokalemia; check K⁺ before insulin
Hyperosmolar hyperglycemic state
Enough insulin to block ketogenesis, not hyperglycemia; type 2, older
Glucose > 600, osmolality > 320, severe dehydration, confusion/coma; little or no acidosis
Aggressive fluids · higher mortality than DKA
Microvascular — mechanisms
Nonenzymatic glycation (AGEs) of proteins → hyaline arteriolosclerosis, thick BM · aldose reductase → sorbitol accumulates in cells lacking sorbitol dehydrogenase
Lens (cataracts), Schwann cells, retina, kidney
Glycemic control prevents
Pericyte loss, microaneurysms, ischemia → VEGF
Nonproliferative: microaneurysms, dot-blot hemorrhages, hard exudates, cotton wool spots · proliferative: neovascularization → vitreous hemorrhage, detachment
Anti-VEGF, laser photocoagulation
Sorbitol + microvascular injury to nerves
Symmetric stocking-glove sensory loss → ulcers, Charcot joints; autonomic (gastroparesis, ED, orthostasis); CN III palsy with pupil sparing
Accelerated atherosclerosis
Coronary artery disease (often silent MI), stroke, peripheral artery disease → gangrene, amputation
Leading cause of death · statins, BP control
Neutrophil dysfunction, poor perfusion, high glucose
Mucormycosis (DKA), malignant otitis externa (Pseudomonas), emphysematous pyelonephritis, foot infections, candidiasis
Black necrotic nasal eschar → Mucor
Monogenic or secondary
MODY (GCK, HNF1A — AD, young, lean) · pancreatitis, CF, hemochromatosis, Cushing, acromegaly, glucagonoma, steroids
HNF1A MODY: very sulfonylurea-sensitive