Trends of earlier and later responses of C-peptide to oral glucose challenges with progression to type 1 diabetes in diabetes prevention trial-type 1 participants

Abstract

OBJECTIVE We studied the C-peptide response to oral glucose with progression to type 1 diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants. RESEARCH DESIGN AND METHODS Among 504 DPT-1 participants <15 years of age, longitudinal analyses were performed in 36 progressors and 80 nonprogressors. Progressors had oral glucose tolerance tests (OGTTs) at baseline and every 6 months from 2.0 to 0.5 years before diagnosis; nonprogressors had OGTTs over similar intervals before their last visit. Sixty-six progressors and 192 nonprogressors were also studied proximal to and at diagnosis. RESULTS The 30-0 min C-peptide difference from OGTTs performed 2.0 years before diagnosis in progressors was lower than the 30-0 min C-peptide difference from OGTTs performed 2.0 years before the last visit in nonprogressors (P < 0.01) and remained lower over time. The 90-60 min C-peptide difference was positive at every OGTT before diagnosis in progressors, whereas it was negative at every OGTT before the last visit in nonprogressors (P < 0.01 at 2.0 years). The percentage whose peak C-peptide occurred at 120 min was higher in progressors at 2.0 years (P < 0.05); this persisted over time (P < 0.001 at 0.5 years). However, the peak C-peptide levels were only significantly lower at 0.5 years in progressors (P < 0.01). The timing of the peak C-peptide predicted type 1 diabetes (P < 0.001); peak C-peptide levels were less predictive (P < 0.05). CONCLUSIONS A decreased early C-peptide response to oral glucose and an increased later response occur at least 2 years before the diagnosis of type 1 diabetes.

Figure 1

A: Glucose curves from OGTTs at baseline and 2.0 and 0.5 years before diagnosis in the progressors, and at baseline and corresponding times before the last visit in the nonprogressors. In both the progressors and nonprogressors, glucose levels increased substantially at all OGTT time points (AUC glucose: P < 0.001 from baseline to 0.5 years in both groups). (Mean values are shown for the times before diagnosis or the last visit.) B: C-peptide curves from OGTTs at baseline and 2.0 and 0.5 years before diagnosis in the progressors, and at baseline and corresponding times before the last visit in the nonprogressors. In the nonprogressors, C-peptide levels increased at all OGTT time points (AUC C-peptide: P < 0.001 from baseline to 0.5 years). In the progressors, although the fasting and 120-min C-peptide levels were higher at 0.5 years than at baseline, there was no significant overall change (AUC C-peptide: P = 0.936 from baseline to 0.5 years). (Mean values are shown for the times before diagnosis or the last visit.)

Figure 2

A: The difference (mean ± SE) in C-peptide levels from 0 to 30 min (the 30–0 min C-peptide difference) according to the times before diagnosis (progressors) or the times before the last visit (nonprogressors). The 30–0 min C-peptide difference was consistently lower in the progressors than in the nonprogressors. (Mean values are shown for the times before diagnosis or the last visit.) B: The difference (mean ± SE) in C-peptide levels from 60 to 90 min (the 90–60 min C-peptide difference) according to the times before diagnosis (progressors) or the times before the last visit (nonprogressors). At every time before diagnosis, the 90–60 min C-peptide difference was positive in the progressors, whereas at every time before the last visit, it was negative in the nonprogressors. (Mean values are shown for the times before diagnosis or the last visit.)

Figure 3

The C-peptide sum after 30 min (mean ± SE) according to the times before diagnosis (progressors) or the times before the last visit (nonprogressors). The values were higher in the progressors from baseline to 0.5 years. (Mean values are shown for the times before diagnosis or the last visit.)

Figure 4

A: The 30–0 min C-peptide difference (mean ± SE) in the progressors who had OGTTs 0.5 years before diagnosis and at diagnosis and in the nonprogressors who had OGTTs 0.5 years before the last visit and at the last visit. The 30–0 min C-peptide difference declined considerably in the progressors. B: The C-peptide sum after 30 min (mean ± SE) in the progressors who had OGTTs 0.5 years before diagnosis and at diagnosis and in the nonprogressors who had OGTTs 0.5 years before the last visit and at the last visit. The C-peptide sum after 30 min declined, but did not fall below that in the nonprogressors.