Which children with diabetes should be screened for maturity-onset diabetes of the young?

Takeaway

• Absence of 4 type 1 diabetes-associated autoantibodies (GAD antibody, insulinoma antigen-2A, zinc transporter 8A, and IAA), and HbA1c <7.5% should trigger testing for maturity-onset diabetes of the young (MODY) genes GCK, HNF1A, and HNF4A.

Why this matters

• A correct MODY diagnosis can allow youth to avoid insulin.

Study design

• Swedish patients (n=3933) ages 1-18 years with diagnosed diabetes mellitus (DM) were tested for the 4 autoantibodies, and MODY was identified through sequencing of the 3 genes.
• Funding:Swedish Child Diabetes Foundation; NIH; National Institute for Health Research (UK); Wellcome Trust.

Key results

• Most (88%, n=3471) had ≥1 autoantibody, none of whom had MODY.
• Factors predicting MODY at diagnosis:
  • Negativity for all 4 autoantibodies (100% vs 11% not-known MODY, P=2×10^-44); 
  • Lower HbA1c, 7.0% vs 10.7% (P=1×10^-20); 
  • Lower random plasma glucose (mean 11.7 vs 26.7 mmol/L; P=3×10^-19); 
  • Parental diabetes (63% vs 12%; P=1×10^-15); and
  • No diabetic ketoacidosis (0/46 vs 601/3887; P=.001).
• Of 303 autoantibody-negative patients genetically tested, 15% had MODY.
• Testing only the 73 autoantibody-negative patients with HbA1c <7.5% identified 49% with MODY.
• At an average 5.9 years after initial diabetes diagnosis, the 46 with MODY had mean HbA1c 6.4%, and 91% were not using insulin.  

Limitations

• Only 3 MODY subtypes tested.
• All-Swedish population.