Genomic Testing for Monogenic Diabetes in the UK: A Three-Fold Increase in Diagnoses Since 2009

Abstract

Background: Maturity Onset Diabetes of the Young (MODY) is a rare monogenic form of diabetes. In 2009, >80% of UK cases were estimated to be misdiagnosed. Since then, there have been a number of initiatives to improve detection of MODY: the Genetic Diabetes Nurse (GDN) education programme, the MODY probability calculator, and targeted next generation sequencing (tNGS). We aimed to determine an up-to-date prevalence estimate for UK MODY and assess how these initiatives have impacted case finding. Methods:UK referrals for genetic testing for monogenic diabetes diagnosed >1y of age from 1/1/1996 to 31/12/2019 were examined. Positive-test rates were compared for referrals reporting involvement of the GDNs/MODY calculator with those that did not. Findings: A diagnosis of MODY was confirmed in 3860 individuals, >3-fold higher than 2009 (n=1177). Median age at diagnosis in probands was 21y. GDN involvement was reported in 21% of referrals; these referrals had a higher positive-test rate than those without GDN involvement (32% v 23%, p<0.001). MODY calculator usage was indicated on 74% of eligible referrals since 2014; these referrals had a higher positive-test rate than those not using the calculator (32% v 24%, p=0.001). 374 (10%) cases were identified through tNGS. MODY prevalence was estimated to be 248 cases/million (double that estimated in 2009 due to increased case-finding). Interpretation: Since 2009, referral rates and case diagnosis has increased three-fold. This is likely to be the consequence of tNGS, GDN education and the MODY calculator. Funding: NIHR, Scottish Government Declaration of Interest: None