Type 1 vs Type 2 Diabetes: Pathophysiology, Diagnosis, and Management
Diabetes questions appear on every major licensing exam, and the details matter: knowing DKA from HHS, insulin onset from duration, and A1c from fasting glucose targets separates the passing score from the comfortable one.
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Type 1: autoimmune, absolute insulin deficiency, antibody-positive
Diagnose with: fasting glucose ≥126, A1c ≥6.5%, random ≥200 with symptoms
DKA: glucose 250–600 + ketoacidosis + AG elevation (Type 1)
Type 1: autoimmune destruction of pancreatic β-cells, absolute insulin deficiency, typically age <30, thin, antibody-positive (anti-GAD, anti-islet cell, anti-insulin). Requires insulin. Type 2: insulin resistance + relative insulin deficiency, typically age >40, obese, strong family history. Managed with lifestyle → oral agents → insulin as disease progresses.
Diagnostic Criteria (ADA)
Any ONE of: (1) Fasting glucose ≥126 mg/dL (8h fast), (2) 2-hour glucose ≥200 mg/dL on oral glucose tolerance test, (3) A1c ≥6.5%, (4) Random glucose ≥200 mg/dL with symptoms (polyuria, polydipsia, unexplained weight loss). Prediabetes: fasting 100–125, A1c 5.7–6.4%, or 2h OGTT 140–199.
DKA vs HHS
DKA (Type 1): glucose typically 250–600, ketoacidosis (pH <7.3, HCO3 <15), anion gap elevated, Kussmaul respirations, fruity breath. HHS (Type 2): glucose >600, minimal ketosis, serum osmolarity >320, profound dehydration, no acidosis. Treatment overlap: IV fluids first, then insulin (after K+ >3.5), K+ replacement, identify precipitant.
1. A 19-year-old presents with 2 weeks of polyuria, polydipsia, and 10 lbs of weight loss. Glucose is 320 mg/dL, pH 7.21, HCO3 11, anion gap 22. What is the diagnosis?
Explanation. DKA: young patient + new-onset symptoms + glucose >250 + acidosis (pH 7.21, HCO3 11) + elevated anion gap. This is classic DKA in a new Type 1 diabetic. HHS would have glucose >600, osmolarity >320, and no significant acidosis.
2. A DKA patient has glucose 380, pH 7.15, and K+ 2.9 mEq/L. The correct next step is:
Explanation. Insulin should not be started until K+ is at least 3.5 mEq/L. Insulin drives K+ into cells, which will worsen hypokalemia — potentially causing fatal arrhythmias. Administer IV potassium first, then reassess before starting insulin.
3. Which insulin type has no peak and provides 24-hour basal coverage?
Explanation. Glargine (Lantus) is a long-acting insulin analog with onset ~1–2 hours and duration ~20–24 hours and no pronounced peak, making it ideal for once-daily basal coverage. NPH has a peak at 4–10 hours and is intermediate-acting.
Frequently asked questions
What is the A1c target for most diabetic patients?
The ADA recommends A1c <7.0% for most non-pregnant adults with diabetes. Less stringent targets (<8.0%) are appropriate for older patients, those with significant comorbidities, short life expectancy, or history of severe hypoglycemia. More stringent (<6.5%) may be reasonable in younger patients with long disease duration if achievable without significant hypoglycemia.
Why do DKA patients have hypokalemia on treatment despite initially normal or high potassium?
Total body potassium is depleted in DKA from osmotic diuresis. However, initial serum K+ may be normal or high because acidosis drives K+ out of cells in exchange for H+. When insulin is given and pH corrects, K+ shifts back intracellularly — causing rapid, dangerous hypokalemia. This is why K+ must be >3.5 before starting insulin, and potassium must be repleted throughout DKA treatment.
What is the first-line oral medication for Type 2 diabetes?
Metformin is the first-line oral agent for Type 2 diabetes in the absence of contraindications. It reduces hepatic glucose production (inhibits gluconeogenesis via AMPK activation), is weight-neutral, has a low hypoglycemia risk, and reduces cardiovascular mortality. Contraindicated in eGFR <30 mL/min/1.73m² and held before contrast administration.
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