Abstract
OBJECTIVE To define the relationship between glucose and C-peptide during the progression to type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS We longitudinally studied glucose and C-peptide response curves (GCRCs), area under curve (AUC) for glucose, and AUC C-peptide from oral glucose tolerance tests (OGTTs), and Index60 (which integrates OGTT glucose and C-peptide values) in Diabetes Prevention Trial–Type 1 (DPT-1) (n = 72) and TrialNet Pathway to Prevention Study (TNPTP) (n = 82) participants who had OGTTs at baseline and fol-low-up time points before diagnosis. RESULTS Similar evolutions of GCRC configurations were evident between DPT-1 and TNPTP from baseline to 0.5 years prediagnosis. Whereas AUC glucose increased throughout from baseline to 0.5 years prediagnosis, AUC C-peptide increased from baseline until 1.5 years prediagnosis (DPT-1, P = 0.004; TNPTP, P = 0.012) and then decreased from 1.5 to 0.5 years prediagnosis (DPT-1, P = 0.017; TNPTP, P = 0.093). This change was mostly attributable to change in the late AUC C-peptide response (i.e., 60-to 120-min AUC C-peptide). Median Index60 values of DPT-1 (1.44) and TNPTP (1.05) progressors to T1D 1.5 years prediagnosis (time of transition from increasing to decreasing AUC C-peptide) were used as thresholds to iden-tify individuals at high risk for T1D in the full cohort at baseline (5-year risk of 0.75–0.88 for those above thresholds). CONCLUSIONS A transition from an increase to a decrease in AUC C-peptide ~1.5 years prediag-nosis was validated in two independent cohorts. The median Index60 value at that time point can be used as a pathophysiologic-based threshold for identifying individuals at high risk for T1D.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2264-2270 |
| Number of pages | 7 |
| Journal | Diabetes care |
| Volume | 45 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2022 |
Bibliographical note
Funding Information:Acknowledgments. The authors acknowledge the support of the Type 1 Diabetes TrialNet Study Group, which identified study participants and provided samples and follow-up data for this study. Members of the Type 1 Diabetes TrialNet Study Group and TrialNet Affiliate Sites are listed in Supplementary Material. Funding. The Type 1 Diabetes TrialNet Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, through cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085453, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106994, U01 DK107013, U01 DK107014, UC4 DK106993, UC4 DK11700901, U01 DK 106693-02, and JDRF. This work was also made possible with support from grants KL2TR002530 (A. Carroll, Principal Investigator [PI]) and UL1TR002529 (A. Shekhar, PI) from the NIH, Clinical and Translational Sciences Award, National Center for Advancing Translational Sciences, and NIH grants R01 DK121843 (to M.J.R.) and R01 DK124395 (to M.J.R.).
Publisher Copyright:
© 2022 by the American Diabetes Association.
