<b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>

<p dir="ltr">Maturity Onset Diabetes of the Young (MODY) can present after the age of 40 years, but its prevalence, clinical characteristics, and the utility of simple clinical features for selecting cases in this age group remain poorly defined. We analysed whole-exome and clinical data from 51,619 individuals with diabetes diagnosed after age 40 from one UK and one US cohort. The prevalence of MODY due to pathogenic variant in the 10 most common MODY genes was 1 in 191 (0.52%) in the UK cohort and 1 in 633 (0.16%) in the US cohort. For subtypes with treatment implications (GCK, HNF1A, HNF4A, ABCC8, KCNJ11), prevalence was 1 in 234 and 1 in 935, respectively. GCK-MODY was most common, followed by HNF4A and lower-penetrance RFX6-MODY. Clinical features of MODY largely overlapped with non-MODY either insulin-treated from diagnosis or not insulin-treated from diagnosis. Only BMI, HbA1c and HDL were statistically different in MODY from non-MODY in both cohorts (all P<0.0018). Applying strict clinical criteria (BMI<25 and noninsulin treated and parent with diabetes) only increased the MODY diagnosis to 2.64% and 0.87% but missed over 86% of cases. MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify.</p>