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

• Published in: The journal of clinical endocrinology and metabolism Vol. 107; no. 8; pp. e3273 - e3280
• Main Authors: Baidal, David A, Warnock, Megan, Xu, Ping, Geyer, Susan, Marks, Jennifer B, Moran, Antoinette, Sosenko, Jay, Evans-Molina, Carmella
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.08.2022
• Subjects: Adolescent; Adult; Autoantibodies; Autoimmunity; Beta cells; Blood Glucose; C-Peptide; Chemical industry; Child; Child, Preschool; Clinical trials; Clinical Trials as Topic; Dextrose; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - drug therapy; Glucose; Glucose tolerance; Glucose Tolerance Test; Glucose tolerance tests; Herbicides; Humans; Insulin; Online Only; Peptides; Pesticides industry; Predictions; Type 1 diabetes; Young Adult; Japan; Index60; TrialNet; type 1 diabetes; C-peptide index; oral glucose tolerance test; first-phase insulin response
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgac285

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.