Background Maturity-onset diabetes of the young (MODY) is autosomal dominant, young-onset, non-insulin dependent diabetes accounting for 2% of diabetes cases and up to 10% before age 35 years. It is frequently misclassified as type 1 or type 2 diabetes. Genetic testing for accurate diagnosis is important to guide therapy and management decisions, which are distinct for the common types of MODY, and identifies affected family members who can benefit from genetic testing. HNF1A-MODY is the most common form worldwide and responds to low doses of sulfonylureas with equivalent or improved glycemic control as compared to insulin therapy.
Aim Here we describe the US Monogenic Diabetes Registry HNF1A-MODY cohort, including phenotype, frequency and duration of diabetes misclassification, and treatment patterns.
Results We currently follow 47 probands and 74 individuals with HNF1A-MODY. Current mean age of probands and the entire cohort is 31.5 years and 33.2 years, respectively. Mean age at diabetes diagnosis was 16.9 years for probands and 18.0 years for the entire cohort. 89% of probands were diagnosed with diabetes <25 years. 76.9% of probands had normal BMIs at time of diagnosis. 82% had 2 or more affected generations with diabetes. Despite the large majority having classic features of MODY, on average, the duration of diabetes diagnosis prior to genetic diagnosis of MODY was 11.8 years. Of the 41 probands providing historical data on medications, 31 (75.6%) report previous use of insulin therapy. Of the 24 probands with current treatment data, 79% are on mono- or combination therapy with sulfonylureas or glinides.
Conclusions The clinical features of MODY have been formally described since the early 1970s with gene causes discovered starting in 1992. However, MODY frequently goes unrecognized. In our cohort, most probands were misclassified for years prior to referral for genetic testing for accurate diagnosis. Sulfonylureas are the established first-line therapy for HNF1A-MODY. A large percentage of subjects were treated with insulin prior to diagnosis with subsequent initiation of sulfonylureas or other insulin secretagogues in 79% of those with current treatment data. The duration of diabetes misclassification coupled with frequent insulin use prior to accurate genetic diagnosis in our HNF1A-MODY cohort underscore the need to increase recognition of MODY among providers.
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