Oral Glucose Tolerance Test Measures of First-Phase Insulin Response and their Predictive Ability for Type 1 Diabetes.

CONTEXT: Decreased first-phase insulin response (FPIR) during intravenous glucose tolerance testing (IVGTT) is an early indicator of β-cell dysfunction and predictor of type 1 diabetes (T1D).

OBJECTIVE: Assess whether oral glucose tolerance test (OGTT) measures could serve as FPIR alternatives in their ability to predict T1D in autoantibody positive (Aab+) subjects.

DESIGN: OGTT and IVGTT were performed within 30 days of each other. Eleven OGTT variables were evaluated for: 1) correlation with FPIR, and 2) T1D prediction.

SETTING: Type 1 Diabetes TrialNet "Oral Insulin for Prevention of Diabetes in Relatives at Risk for T1D" (TN-07) and Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) studies clinical sites.

PATIENTS: TN-07 (n=292; age 9.4±6.1 years) and DPT-1 (n=194; age 15.1±10.0 years) Aab+ relatives of T1D individuals.

MAIN OUTCOME MEASURES: 1) Correlation coefficients of OGTT-measures with FPIR, and 2) T1D prediction at 2-years using area under receiver operating characteristic (ROCAUC) curves.

RESULTS: Index60 showed the strongest correlation in DPT-1 (r=-0.562) but was weaker in TN-07 (r=-0.378). C-peptide index consistently showed good correlation with FPIR across studies (TN-07, r=0.583; DPT-1, r=0.544; p<0.0001). Index60 and C-peptide index had the highest ROCAUCs for T1D prediction (0.778 vs. 0.717 in TN-07; 0.763 vs. 0.721 in DPT-1, respectively; p=NS), followed by FPIR (0.707 in TN-07; 0.628 in DPT-1).

CONCLUSIONS: C-peptide index was the strongest measure to correlate with FPIR in both studies. Index60 and C-peptide index had the highest predictive accuracy for T1D and were comparable. OGTTs could be considered instead of IVGTTs for subject stratification in T1D prevention trials.