Bit · Endo
Type 1 vs Type 2 Diabetes Mellitus
Two diseases that share the chief complaint of hyperglycemia but split mechanistically. One is autoimmune insulin deficiency; the other is insulin resistance with relative deficiency.
Mechanism
Both produce chronic hyperglycemia with microvascular and macrovascular complications. The mechanism is opposite:
- Type 1 DM — autoimmune destruction of pancreatic β cells (HLA-DR3, HLA-DR4 associations). Absolute insulin deficiency. Antibodies (anti-GAD, anti-islet cell, anti-insulin) confirm diagnosis. Onset typically in childhood/adolescence but can occur at any age. Lean body habitus. Risk of DKA (because no insulin means free fatty acid flux from adipose tissue → ketogenesis). Must take exogenous insulin.
- Type 2 DM — peripheral insulin resistance + progressive β-cell secretory failure. Relative insulin deficiency. Onset typically in adults (now increasingly in obese adolescents). Strong genetic component. Risk factors: obesity, sedentary lifestyle, family history, certain ethnic groups. Usually presents indolently — diagnosed on screening or with complications. DKA can occur but is less common; HHS more typical (small amount of residual insulin suppresses ketogenesis but glucose runs to 1000+). Treat: lifestyle + metformin first; insulin reserved for advanced disease.
Both share complications: microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (CAD, stroke, peripheral arterial disease).
Differentiator Table
| Type 1 DM | Type 2 DM | |
| Mechanism | Autoimmune β-cell destruction | Peripheral insulin resistance + β-cell failure |
| Insulin level | Absent (absolute deficiency) | Initially ↑ then ↓ (relative deficiency) |
| HLA association | HLA-DR3, DR4 | None |
| Antibodies | Anti-GAD, anti-islet, anti-insulin | None |
| Age of onset | Typically < 30 (peak childhood/adolescence) | Typically > 40 (rising in obese youth) |
| Body habitus | Lean | Often obese |
| Family history | Less strong (concordance in twins ~50%) | STRONG (twin concordance ~90%) |
| Presenting acute decompensation | DKA (no insulin → ketogenesis) | HHS (residual insulin suppresses ketones; glucose >1000) |
| First-line treatment | Insulin (lifelong) | Lifestyle + metformin |
| C-peptide | Low / absent | Normal or elevated early, low late |
| Diagnostic criteria (both) | HbA1c ≥ 6.5%; fasting glucose ≥ 126; 2-h OGTT ≥ 200; random glucose ≥ 200 with symptoms (confirm) | Same |
The Pivot
Two questions:
- Lean child or adolescent presenting in DKA with weight loss? → Type 1.
- Overweight middle-aged adult, asymptomatic on screening or with mild polyuria/polydipsia? → Type 2.
Confirm with C-peptide and autoantibodies: low C-peptide + positive antibodies → T1DM. Normal/elevated C-peptide, no antibodies → T2DM.
Don't be fooled by adults presenting like T1DM — LADA (latent autoimmune diabetes of adults) is autoimmune but presents in adulthood; antibodies will be positive.
NBME-Style Stem
A 13-year-old boy is brought to the ED with 3 weeks of polyuria, polydipsia, and 4 kg weight loss, now with nausea and confusion. Examination shows deep, rapid breathing and dry mucous membranes. Glucose is 612 mg/dL, bicarbonate is 9 mEq/L, anion gap is 28, urine ketones are 4+. Anti-GAD antibodies are positive. Which of the following is the most likely diagnosis?
Concept Anchor
Type 1 is no insulin (autoimmune); type 2 is insulin that doesn't work (resistance + late failure). The acute decompensation each takes — DKA for type 1, HHS for type 2 — reflects whether enough insulin is around to suppress ketogenesis.