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PubMed ID:
38767115
Public Release Type:
Journal
Publication Year: 2024
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.
DOI:
https://doi.org/10.1210/clinem/dgae349
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
Request IDs:
22822
Studies:
ATG-GCSF in New Onset Type 1 Diabetes
,
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus
,
Preservation of Pancreatic Production of Insulin Through Immunosuppression
,
The Effects of Rituximab on the Progression of Type 1 Diabetes in New Onset Subjects
,
TN10 Anti-CD3 Prevention
,
TrialNet 08: Effects of Recombinant Human Glutamic Acid Decarboxylase (rhGAD65) Formulated in Alum (GAD-alum) on the Progression of Type 1 Diabetes in New Onset Subjects
,
TrialNet 09: Effects of CTLA-4 IG (Abatacept) on the Progression of Type 1 Diabetes in New Onset Subjects
,
TrialNet 14: Effects of Canakinumab on the Progression of Type 1 Diabetes in New Onset Subjects
,
TrialNet 18 -CTLA-4 Ig (Abatacept) for Prevention of abnormal glocose tolerance and diabetes in relatives at-risk for Type 1 Diabetes Mellitus
,
TrialNet Pathway To Prevention (formerly Natural History Study)
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.
