The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in β-Cell Function in TODAY
Year: 2018
Type: article
Abstract: OBJECTIVE Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired β-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in β-cell function. RESEARCH DESIGN AND METHODS OGTTs (n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (△C30/△G30), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups. RESULTS At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) (P < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity. CONCLUSIONS In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced β-cell function and foretells increased glycemic failure rates with accelerated deterioration in β-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes.
Source: Diabetes Care
DOI: 10.2337/dc18-1122
Authors: Silva Arslanian, Laure El ghormli, Joon Young Kim, Fida Bacha, Christine Chan, Heba M. Ismail, Lorraine E. Levitt Katz, Lynne Levitsky, Jeanie B. Tryggestad, Neil H. White, TODAY Study Group, S. McKay, M. Haymond, B. Anderson, C. Bush, S. Gunn, H. Holden, S.M. Jones, G. Jeha, S. McGirk, S. Thamotharan, L. Cuttler, E. Abrams, T. Casey, W. Dahms, C. Ievers-Landis, B. Kaminski, M. Koontz, S. MacLeish, P. McGuigan, S. Narasimhan, M. Geffner, V. Barraza, N. Chang, B. Conrad, D. Dreimane, S. Estrada, L. Fisher, E. Fleury-Milfort, S. Hernandez, B. Hollen, F. Kaufman, E. Law, V. Mansilla, D. Miller, C. Muñoz, R. Ortiz, A. Ward, K. Wexler, Y.K. Xu, P. Yasuda, L. Levitt Katz, R. Berkowitz, S. Boyd, B. Johnson, J. Kaplan, C. Keating, C. Lassiter, T. Lipman, G. McGinley, H. McKnight, B. Schwartzman, S. Willi, S. Arslanian, F. Bacha, S. Foster, B. Galvin, T. Hannon, A. Kriska, I. Libman, M. Marcus, K. Porter, T. Songer, E. Venditti, R. Goland, D. Gallagher, P. Kringas, N. Leibel, D. Ng, M. Ovalles, D. Seidman, L. Laffel, A. Goebel-Fabbri, M. Hall, L. Higgins, J. Keady, M. Malloy, K. Milaszewski, L. Rasbach, D.M. Nathan, A. Angelescu, L. Bissett, C. Ciccarelli, L. Delahanty, V. Goldman, O. Hardy, M. Larkin, L. Levitsky, R. McEachern, D. Norman, D. Nwosu, S. Park-Bennett, D. Richards, N. Sherry, B. Steiner, S. Tollefsen, S. Carnes, D. Dempsher, D. Flomo, T. Whelan, B. Wolff, R. Weinstock, D. Bowerman, S. Bristol, J. Bulger, J. Hartsig, R. Izquierdo, J. Kearns, R. Saletsky, P. Trief, P. Zeitler, N. Abramson, A. Bradhurst, N. Celona-Jacobs, J. Higgins, M. Kelsey, G. Klingensmith, K. Nadeau, T. Witten, K. Copeland, E. Boss, R. Brown, J. Chadwick, L. Chalmers, S. Chernausek, A. Hebensperger, C. Macha, R. Newgent, A. Nordyke, D. Olson, T. Poulsen, L. Pratt, J. Preske, J. Schanuel, S. Sternlof, J. Lynch, N. Amodei, R. Barajas, C. Cody, D. Hale, J. Hernandez, C. Ibarra, E. Morales, S. Rivera, G. Rupert, A. Wauters, N. White, A. Arbeláez, D. Flomo, J. Jones, T. Jones, M. Sadler, M. Tanner, A. Timpson, R. Welch, S. Caprio, M. Grey, C. Guandalini, S. Lavietes, P. Rose, A. Syme, W. Tamborlane, K. Hirst, S. Edelstein, P. Feit, N. Grover, C. Long, L. Pyle, B. Linder, S.M. Marcovina, J. Harting, J. Shepherd, B. Fan, L. Marquez, M. Sherman, J. Wang, M. Nichols, E. Mayer-Davis, Y. Liu, J. Lima, S. Gidding, J. Puccella, E. Ricketts, R. Danis, A. Domalpally, A. Goulding, S. Neill, P. Vargo, D. Wilfley, D. Aldrich-Rasche, K. Franklin, C. Massmann, D. O’Brien, J. Patterson, T. Tibbs, D. Van Buren, M. Palmert, R. Ratner, D. Dremaine, J. Silverstein
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: American Diabetes Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, GlaxoSmithKline, Sanofi, LifeScan, Massachusetts General Hospital, Children's Hospital of Philadelphia, Washington University in St. Louis, University of Oklahoma, BD, National Institutes of Health, University of Oklahoma Health Sciences Center, University of Colorado Denver, Washington University School of Medicine in St. Louis, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, NIH Clinical Center, National Center for Advancing Translational Sciences, Children's Hospital of Pittsburgh
Awards: Management of Pediatric Type 2 Diabetes Mellitus, Multi-Center Study of the Treatment of T2DM in Youth, G20368179, Harvard Clinical and Translational Science Center (UL1), General Clinical Research Center, University of Pittsburgh Clinical and Translational Science Institute, Type 2 Diabetes in Youth: Beta Cell Preservation, Treatment Alternatives in Pediatric Type 2 Diabetes, TODAY2 Phase 2 (T2P2): Long-Term Post-Intervention Follow-Up, Institutional Clinical and Translational Science Award, General Clinical Research Center, General Clinical Research Center, Washington University Institute of Clinical and Translational Sciences (UL1), General Clinical Research Center, G9000042762, T32 Research Training in Diabetes and Endocrinology, Washington University Institute of Clinical and Translational Sciences, Yale Diabetes Research Center, GENERAL CLINICAL RESEARCH CENTER, Colorado Clinical and Translational Science Institute (UL1)
OpenAlex ID: W2900979192