Monogenic Diabetes Misdiagnosed as Type 1: A Narrative Review of When to Test for MODY
DOI:
https://doi.org/10.5281/zenodo.22258315Keywords:
Monogenic diabetes, MODY, C-peptide, Genetic testing, MisdiagnosisAbstract
Monogenic diabetes accounts for roughly 1 to 3 per cent of diabetes diagnosed before the age of 25, and the diagnosis matters
because it changes treatment: several subtypes respond to sulfonylurea rather than insulin, and one usually requires no treatment
at all. It is nonetheless missed. In a diabetes centre cohort of 97 patients with onset before 25, detectable C-peptide and negative
autoantibodies, 22 were found to carry a pathogenic variant, and only one of those 22 had been given the correct diagnosis before
genetic testing. Yield depends almost entirely on how patients are selected: 2.1 per cent in an unselected childhood cohort, 8.2 per
cent among those who were autoantibody-negative with detectable C-peptide, and 21 per cent under narrow clinical criteria.
About 10 per cent of people with type 1 diabetes of European ancestry have no detectable islet autoantibodies, rising to 28 per
cent in other populations, and in one cohort of 482 such patients MODY accounted for 2.5 per cent. This review sets out who
should be tested and what the testing does not settle.
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