Introduction and Objective: Monogenic diabetes (MD) accounts for 0.4% of all cases of diabetes and 1-5% of youth-onset diabetes. Diagnosis allows for improved care with targeted therapy and identification of affected relatives. However, several barriers currently prevent patients from receiving diagnoses. We aimed to elucidate the proportion of individuals with undiagnosed MD within the Rare and Atypical Diabetes Network (RADIANT), a multicenter, national research study that aims to identify and characterize individuals with unknown forms of diabetes.Methods: Medical and family history of consented participants were reviewed by an Adjudication Committee of diabetes and genetic experts to determine eligibility for genome sequencing (GS). MD testing was recommended for those with suspected MD prior to GS. We evaluated MD testing outcomes among participants who had no MD testing prior to study enrollment but met Adjudication Committee criteria for testing.Results: Of 1,117 participants reviewed by the Adjudication Committee, MD testing was recommended for 123 who had no prior MD testing (average age 43 years, 73% female, BMI 24 kg/m2, HbA1c 8.3%). Of the 123 individuals, 85 obtained testing. MD was diagnosed in 36 participants (diagnostic yield 42%). Identified cases had variants in 8 different MD genes (GCK n=15, HNF1A n=10, HNF4A n=3, HNF1B n=2, KCNJ11 n=2, ABCC8 n=2, LMNA n=2, mtDNA m.3243A>G n=2). Genetic testing had been considered for 46 of the 122 participants prior to RADIANT enrollment. The most common barriers to obtain testing prior to enrollment were cost (19/46, 41%) and provider uncertainty regarding testing (12/46, 26%).Conclusion: Approximately 10% of RADIANT participants were recommended for MD testing in the clinical setting. The diagnostic yield among the 85 who obtained testing was 42%, or 29% (36/123) of those recommended for testing. Increased awareness of MD among clinicians is needed to improve case detection and outcomes in people with MD.
J.L. Douvas: None. K.A. Maloney: None. L.R. Letourneau-Freiberg: None. R.J. Kreienkamp: None. T.I. Pollin: None. M. Udler: Research Support; Novo Nordisk. K.R. Klein: Consultant; Novo Nordisk, Roche Pharmaceuticals.
The RADIANT Study is funded by U54 DK118638 and U54 DK118612 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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