Ismail, Heba M.Becker, Dorothy J.Libman, IngridHerold, Kevan C.Redondo, Maria J.Atkinson, Mark A.Cleves, Mario A.Palmer, JerrySosenko, Jay2021-01-252021-01-252020-01-31Ismail, H. M., Becker, D. J., Libman, I., Herold, K. C., Redondo, M. J., Atkinson, Cleves, M. A., Palmer, J., Sosenko, J., & Diabetes Prevention Trial-Type 1 (DPT-1) Study Group. (2020). Early and late C-peptide responses during oral glucose tolerance testing are oppositely predictive of type 1 diabetes in autoantibody-positive individuals. Diabetes, Obesity and Metabolism, 22(6), 997–1000. https://doi.org/10.1111/dom.139821462-8902https://hdl.handle.net/1805/24987We examined whether the timing of the C-peptide response during an oral glucose tolerance test (OGTT) in relatives of patients with type 1 diabetes (T1D) is predictive of disease onset. We examined baseline 2-h OGTTs from 670 relatives participating in the Diabetes Prevention Trial-Type 1 (age: 13.8 ± 9.6 years; body mass index z score: 0.3 ± 1.1; 56% male) using univariate regression models. T1D risk increased with lower early C-peptide responses (30–0 min) (χ2 = 28.8, P < 0.001), and higher late C-peptide responses (120–60 min) (χ2 = 23.3, P < 0.001). When both responses were included in a proportional hazards model, they remained independently and oppositely associated with T1D, with a stronger overall association for the combined model than either response alone (χ2 = 41.1; P < 0.001). Using receiver operating characteristic curve analysis, the combined early and late C-peptide response was more accurately predictive of T1D than area under the curve C-peptide (P = 0.005). Our findings demonstrate that lower early and higher late C-peptide responses serve as indicators of increased T1D risk.en-USC-peptideoral glucose tolerance testtype 1 diabetesArticle