Oral Glucose Tolerance Test Measures of First-phase Insulin Response and Their Predictive Ability for Type 1 Diabetes

Abstract

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 and 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.

Keywords: C-peptide index; Index60; TrialNet; first-phase insulin response; oral glucose tolerance test; type 1 diabetes.