Children’s Nutrition Research Center Staff Publications
Language
English
Publication Date
3-17-2025
Journal
The Journal of Clinical Endocrinology & Metabolism
DOI
10.1210/clinem/dgae349
PMID
38767115
PMCID
PMC11913082
PubMedCentral® Posted Date
5-20-2024
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Humans, Diabetes Mellitus, Type 1, C-Peptide, Female, Male, Polymorphism, Single Nucleotide, Retrospective Studies, Genetic Predisposition to Disease, Adult, Adolescent, Child, Young Adult, Glucose Tolerance Test, Family, Autoantibodies, Genetic Association Studies
Published Open-Access
yes
Recommended Citation
Triolo, Taylor M; Parikh, Hemang M; Tosur, Mustafa; et al., "Genetic Associations With C-peptide Levels Before Type 1 Diabetes Diagnosis in At-risk Relatives" (2025). Children’s Nutrition Research Center Staff Publications. 306.
https://digitalcommons.library.tmc.edu/staff_pub/306
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Dietetics and Clinical Nutrition Commons, Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Genetics Commons, Nutrition Commons