David A Baidal1, Megan Warnock2, Ping Xu3, Susan Geyer4, Jennifer B Marks1, Antoinette Moran5, Jay Sosenko1, Carmella Evans-Molina6. 1. Department of Medicine and the Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL 33136, USA. 2. Data Analysis & Research, Office of Data Management & Information Systems, West Virginia Department of Education, Charleston, WV 25305, USA. 3. Late Development Statistics, Biostatistics and Research Decision Sciences, Merck Research Laboratories, Rahway, NJ 07065-4607, USA. 4. Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA. 5. Department of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA. 6. Departments of Medicine and Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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.
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.
Authors: Jay M Sosenko; Jeffrey Mahon; Lisa Rafkin; John M Lachin; Heidi Krause-Steinrauf; Jeffrey P Krischer; David Cuthbertson; Jerry P Palmer; Clinton Thompson; Carla J Greenbaum; Jay S Skyler Journal: Pediatr Diabetes Date: 2011-03 Impact factor: 4.866
Authors: Kristina M Utzschneider; Ronald L Prigeon; Mirjam V Faulenbach; Jenny Tong; Darcy B Carr; Edward J Boyko; Donna L Leonetti; Marguerite J McNeely; Wilfred Y Fujimoto; Steven E Kahn Journal: Diabetes Care Date: 2008-10-28 Impact factor: 19.112