FFinalistSouthampton · 2027
Endocrine
AKT · Endocrine/Diabetes & glucoselow yield

MODY (maturity-onset diabetes of the young)

Monogenic (autosomal dominant) β-cell dysfunction

Overview

Monogenic diabetes from a single autosomal-dominant gene defect (commonly HNF1A, HNF4A, glucokinase/GCK), presenting in young, non-obese, antibody-negative people with a strong vertical family history. Important because it is often misdiagnosed as T1DM (and over-insulinised) — many forms respond to sulfonylureas, and GCK-MODY needs no treatment.

Recognise

  • Young (<25), non-obese, antibody-NEGATIVE diabetes with preserved C-peptide and a strong autosomal-dominant family history (diabetes in successive generations)
  • HNF1A/HNF4A-MODY: progressive hyperglycaemia, sensitive to low-dose SULFONYLUREAS
  • GCK-MODY: mild, stable, non-progressive fasting hyperglycaemia, usually needs no treatment

Red flags

  • Mislabelled as T1DM and put on insulin unnecessarily, or as T2DM — genetic testing changes management

Differentials & how to tell them apart

Type 1 diabetesantibody-positive, low C-peptide, ketosis, insulin-dependent
Type 2 diabetesobese, insulin-resistant, older, not a clean AD pedigree

Investigations

Islet autoantibodies (negative), C-peptide (preserved), genetic testing; strong family history pedigree.

Management

Genetic confirmation → sulfonylurea (HNF1A/4A) or no treatment (GCK)

  1. 1Suspect in young, lean, antibody-negative diabetes with a strong AD family history → genetic testing.Gate: Subtype determines treatment: HNF1A/HNF4A respond to low-dose SULFONYLUREAS (can come off insulin); GCK-MODY needs NO treatment — so don't reflexively insulinise
  2. 2Treat per genotype; counsel family (50% inheritance); GCK-MODY in pregnancy is managed specially.
Sulfonylurea (HNF1A/HNF4A-MODY) — often replaces insulin — exquisitely sensitive
No treatment (GCK-MODY) — benign, stable fasting hyperglycaemia

Key points

Young + lean + antibody-negative + AD family history = think MODY, not T1DM. Genotype changes everything: sulfonylurea-responsive or no treatment at all.

Monitor & prognosis

Per subtype; family screening.

Good; depends on subtype.

Source: Diabetes Genes (Exeter); StatPearls