Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration
Year: 2021
Type: other
Abstract: Objective: Maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multi-ethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes. Research design and methods: We evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. Results: 93 of 3,333 participants (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs 13.6 ± 2.3 years, P=0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs 4.7 ± 3.5 ng/mL, P<0.0001). Youth with MODY were less likely to have hypertension (6.9% vs 19.5%, P=0.007) and had higher HDL cholesterol (43.8 vs 39.7 mg/dL, P=0.006). Conclusions: By comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n=83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria to select individuals for genetic testing.
Authors: Jennifer N. Todd, Jeffrey W. Kleinberger, Haichen Zhang, Shylaja Srinivasan, Sherida E. Tollefsen, Lynne L. Levitsky, Lorraine E. Levitt Katz, Jeanie B. Tryggestad, Fida Bacha, Giuseppina Imperatore, Jean M. Lawrence, Catherine Pihoker, Jasmin Divers, Jason Flannick, Dana Dabelea, Jose C. Florez, Toni I. Pollin
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4245807346