Early and Late C‐peptide Responses during Oral Glucose Tolerance Testing are Oppositely Predictive of Type 1 Diabetes in Autoantibody Positive Individuals

We 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) (chi(2) = 28.8, P < 0.001), and higher late C-peptide responses (120-60 min) (chi(2) = 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 (chi(2) = 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.