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

Abstract

Diabet. Med. 28, 1028–1033 (2011) Abstract Aim Maturity‐onset diabetes of the young is a monogenic form of familial, young‐onset diabetes. It is rare (∼1% diabetes) and may be misdiagnosed as Type 1 diabetes and inappropriately treated with insulin. Type 1 diabetes is characterized by the presence of islet autoantibodies, including glutamate decarboxylase (GAD) and islet antigen‐2 (IA‐2) antibodies. The prevalence of islet autoantibodies is unknown in maturity‐onset diabetes of the young and may have the potential to differentiate this form of diabetes from Type 1 diabetes. The aim of this study was to determine the prevalence of GAD and IA‐2 antibodies in patients with maturity‐onset diabetes of the young and Type 1 diabetes. Methods We measured plasma GAD and IA‐2 antibodies in 508 patients with the most common forms of maturity‐onset diabetes of the young (GCK: n = 227; HNF1A: n = 229; HNF4A: n = 52) and 98 patients with newly diagnosed Type 1 diabetes (diagnosed < 6 months). Autoantibodies were considered positive if ≥ 99th centile of 500 adult control subjects. Results GAD and/or IA‐2 antibodies were present in 80/98 (82%) patients with Type 1 diabetes and 5/508 (< 1%) patients with maturity‐onset diabetes of the young. In the cohort with Type 1 diabetes, both GAD and IA‐2 antibodies were detected in 37.8% of patients, GAD only in 24.5% and IA‐2 only in 19.4%. All five patients with maturity‐onset diabetes of the young with detectable antibodies had GAD antibodies and none had detectable IA‐2 antibodies. Conclusion 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.