Genetic Associations with C-peptide Levels before Type 1 Diabetes Diagnosis in At-Risk Relatives

We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms (SNPs) are associated with C-peptide preservation before type 1 diabetes diagnosis. 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 SNPs and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis. Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before diagnosis in univariate (β=-0.06, P