Type 2 Diabetes Mellitus: A High-Yield USMLE Review

Type 2 diabetes mellitus is a chronic disorder of glucose regulation driven by insulin resistance and progressive beta-cell dysfunction, defined and tracked by elevated HbA1c and fasting glucose. It is fundamentally a disease of blood vessels: every management decision must weigh not just the glucometer number but the heart, kidneys, eyes, and feet that depend on healthy vessels. On the exam it is tested through complication screening, cardiorenal-protective drug selection, and recognizing emergencies like DKA.

Presentation

• Frequently diagnosed with elevated HbA1c (e.g., 8.2–10.8%) and elevated fasting glucose (e.g., 310 mg/dL) in a patient who may have been hyperglycemic for years before diagnosis
• Microvascular complications: diabetic retinopathy, neuropathy, and nephropathy (albuminuria)
• Common comorbidities: hypertension, obesity, and dyslipidemia
• Often accompanies established atherosclerotic cardiovascular disease, such as a prior myocardial infarction
• May present with chronic kidney disease (reduced eGFR, elevated urine albumin-to-creatinine ratio)

Diagnosis

• HbA1c: elevated, both confirming diagnosis and used to track glycemic trajectory over time (checked every 3 months until at goal, then every 6 months)
• Fasting glucose: elevated (e.g., 310 mg/dL) supporting the diagnosis
• Renal assessment: monitor urine albumin-to-creatinine ratio (UACR) and eGFR to stage nephropathy and CKD
• Dilated eye exam at the time of diagnosis (patients may have had diabetes for years), then annually, to screen for retinopathy

Management

• Lifestyle foundation: medical nutrition therapy (reduce refined carbs, emphasize fiber), physical activity (150 min/week moderate intensity), and weight loss
• Metformin is first-line pharmacotherapy, titrated to target dose; set an individualized HbA1c goal (e.g., <7% is reasonable given age and complications)
• Add an SGLT2 inhibitor (e.g., empagliflozin, dapagliflozin) for renal protection and cardiovascular benefit, or a GLP-1 receptor agonist (e.g., semaglutide, liraglutide) for weight loss and cardiovascular benefit; both may be combined
• In patients with established ASCVD, preferentially add a GLP-1 RA or SGLT2 inhibitor with proven MACE and mortality reduction
• Treat comorbidities: ACE inhibitor or ARB for hypertension and nephropathy, a statin for cardiovascular prevention, and consider aspirin (shared decision for primary prevention)
• Ongoing screening: dilated eye exam, annual foot exam with patient education, and monitoring of UACR and eGFR

High-yield

• "Diabetes is a disease of blood vessels" — always consider the heart, kidneys, eyes, and feet, not just glucose
• In established ASCVD, choose a GLP-1 receptor agonist or SGLT2 inhibitor — both have proven cardiovascular and mortality benefit; DPP-4 inhibitors are CV-neutral, sulfonylureas offer no CV benefit and cause hypoglycemia, and thiazolidinediones risk heart failure
• Euglycemic DKA is a recognized complication of SGLT2 inhibitors: acidosis and strongly positive ketones with near-normal glucose, triggered by illness, fasting, or reduced carbohydrate intake
• Type 2 diabetics need a dilated eye exam at diagnosis because they may have been hyperglycemic for years (Type 1 patients start screening 5 years after diagnosis)
• Diabetic retinopathy progression: pericyte loss → microaneurysms → capillary leakage → ischemia → neovascularization; macular edema is treated with anti-VEGF injections or laser

Pitfalls

• Being fooled by a "normal" glucose in a patient on an SGLT2 inhibitor — euglycemic DKA still requires DKA treatment (fluids, insulin, potassium monitoring)
• In DKA, giving insulin before checking potassium: acidosis shifts K+ out of cells masking depleted total-body stores, and insulin drives K+ into cells, risking fatal arrhythmia (hold insulin if K+ <3.3)
• Choosing a glucose-lowering agent for HbA1c reduction alone in a patient with ASCVD or CKD, missing the drugs with proven cardiorenal benefit
• Overlooking the caution needed with metformin as eGFR falls, and the increased hypoglycemia risk of sulfonylureas in CKD