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Publication Information
Affiliation
1Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus.
2Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
3Department of Pediatrics, Division of Diabetes and Endocrinology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
4USDA/ARS Children's Nutrition Research Center, Houston, TX, USA.
5University of Exeter.
6University of Virginia School of Medicine.
Authors
Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo
Abstract
Objective
We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.
Methods
We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.
Results
Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before diagnosis in univariate (β = −.06, P < .0001) and multivariate (β = −.03, P = .005) analyses. Participants with the JAZF1 rs864745 T allele had lower C-peptide AUC in both univariate (β = −.11, P = .002) and multivariate (β = −.06, P = .018) analyses.
Conclusion
The type 2 diabetes-associated JAZF1 rs864745 T allele and higher T1D-GRS2 are associated with lower C-peptide AUC before diagnosis of type 1 diabetes, with implications for the design of prevention trials.