Islet autoantibodies can discriminate maturity‐onset diabetes of the young (MODY) from Type 1 diabetes

Abstract

The prevalence of GAD and IA-2 antibodies in maturity-onset diabetes of the young is the same as in control subjects (< 1%). The finding of islet autoantibodies, especially IA-2 antibodies, makes the diagnosis of maturity-onset diabetes of the young very unlikely and genetic testing should only be performed if other clinical characteristics strongly suggest this form of diabetes rather than Type 1 diabetes. This supports routine islet autoantibody testing before proceeding to more expensive molecular genetic testing.

Towards a systematic nationwide screening strategy for MODY

“…Therefore, none of the results in the antibody-positive cohort would result in a change in the management of the patient's diabetes. This is a reassuring finding for their proposed population screening approach, suggesting very few cases are likely to be missed, and is consistent with what would be expected given previous case-control studies [13], demonstrating the limited use of diagnostic molecular genetic testing for MODY in antibody-positive patients. For the 11 antibody-negative patients who had class 3 variants of unknown pathogenicity, only three of these variants would have been reported by the UK clinical diagnostic testing laboratory, and additional information would have been required from both the affected individual and family members to fully determine pathogenicity.…”

“…By ruling out those with markers of type 1 diabetes, the most common form of diabetes in this age group, they leave a much lower number of more appropriate individuals on which to perform genetic testing. Furthermore, positive islet autoantibody levels are rare in MODY patients, with rates similar to that seen in the non-diabetic population [13], so the number of cases missed by this approach should be minimal.…”

Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry

“…We did not screen all the 3882 children with type 1 diabetes in the NCDR. Genetic screening of children who were positive for only one of the two autoantibodies might increase the diagnostic yield [26]. We did not include antibodies against insulin and zinc transporter 8 (ZnT8) in our study since these were not part of routine antibody screening when the NCDR started in 2002.…”

Clinical utility gene card for: Maturity-onset diabetes of the young

“…GAD and IA2 autoantibodies are present in up to 90-95% of newly diagnosed type 1 diabetes patients, 23 but are present in only 1% of patients with MODY. 24 Testing for GAD and IA2 auto-antibodies is recommended even long after the onset of diabetes, as recent study showed that at least one antibody (GAD and/or IA2) was present in 56% of type 1 diabetes patients after a 19-year median duration of the disease. 25 Urinary and serum C-peptide levels persist in patients with MODY, but are significantly reduced or undetectable in both adult and paediatric type 1 diabetes cases of long duration.…”