Monogenic diabetes (MDM), caused by a single gene or chromosomal abnormality, affects ~2% of people diagnosed with diabetes under 35 years of age, but is frequently misdiagnosed and mistreated. The Monogenic Diabetes Registry began in 2008, and has served to diagnose and longitudinally follow individuals with congenital diabetes and MODY. Research-based genetic testing and pragmatic cohort studies have clarified genotype-phenotype correlations and barriers to diagnosis and appropriate management. Interested participants complete a secure web-based registration form. They are screened and consented by phone or in-person. Participants provide medical and family history information at baseline and annually thereafter via REDCap, as well as DNA samples that are stored in laboratory databases. The Registry has grown exponentially from 430 total participants enrolled by 2009 to over 3,600 participants, from 1,900 families, with an average yearly increase of 38.5%. Fifty-seven percent were referred to the Registry through their diabetes provider. To date, 1,050 participants have a confirmed genetic diagnosis. The majority of testing has been completed through our lab (73%), followed by commercial labs (22%) and other research labs (5%). The average time for an MDM diagnosis is 10 years. The most common cause of MODY in the Registry is GCK-MODY (60%) while the most common cause of congenital diabetes is mutations in KCNJ11 (38%). Of those with baseline survey data on insulin use, 81% were found to have a genetic cause of MDM typically amenable to oral therapies or no treatment. The Registry provides a robust network of MDM resources and support to participants and providers throughout the United States. However, research-based diagnosis has constraints not faced by commercial labs. The long delay in diagnosis and high proportion of research-based testing suggests that broader access to clinical testing via insurance coverage is critically needed.
A. Harris: None. R.N. Naylor: None. M. Sanyoura: None. S.W. Greeley: None. B. Kandasamy: None. L.H. Philipson: None. L.R. Letourneau-Freiberg: None.
National Institutes of Health (R01DK104942, P30DK020595, K23DK094866, UL1TR000430)