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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

2018; American Diabetes Association; Volume: 42; Issue: 1 Linguagem: Inglês

10.2337/dc18-1122

1935-5548

Silva Arslanian, Laure El ghormli, Joon Young Kim, Fida Bacha, Christine L. Chan, Heba M. Ismail, Lorraine E. Levitt Katz, Lynne L. Levitsky, Jeanie B. Tryggestad, Neil H. White, Siripoom McKay, M. Haymond, Barbara J. Anderson, C. Bush, Sheila Gunn, H. Holden, Steven M. Jones, George Jeha, S. McGirk, Shanthie Thamotharan, Leona Cuttler, E. Abrams, Terri Casey, W. Dahms, Carolyn E. Ievers‐Landis, Beth A. Kaminski, Michaela B. Koontz, Sarah A. MacLeish, Paul McGuigan, Sumana Narasimhan, Mitchell E. Geffner, V. Barraza, Nancy Chang, Bernard Conrad, Daina Dreimane, S. Estrada, Lynda K. Fisher, Evelyne Fleury‐Milfort, S. Hernández, B. Hollen, Francine Kaufman, Ernest H. Law, V. Mansilla, Debra L. Miller, Cynthia Muñoz, R. Ortiz, A. Ward, K. Wexler, Yidong Xu, Patrice Yasuda, Lorraine Levitt Katz, Robert J. Berkowitz, S. Boyd, B. Johnson, J. Kaplan, C. Keating, C. A. Lassiter, Terri H. Lipman, G. McGinley, Heather McKnight, B. Schwartzman, Steven M. Willi, S Arslanian, Fida Bacha, Simon R. Foster, Bryan Galvin, Tamara S. Hannon, Andrea M. Kriska, Ingrid Libman, Marsha D. Marcus, Kristin E. Porter, Thomas J. Songer, Elizabeth M. Venditti, Robin Goland, Dympna Gallagher, P. Kringas, Natasha Leibel, Daniel P. K. Ng, M. Ovalles, Daniel S. Seidman, Lori M. Laffel, Ann Goebel-Fabbri, Michael Hall, Linda W. Higgins, Joyce Keady, M. Malloy, Kerry Milaszewski, Lisa Rasbach, David M. Nathan, A. Angelescu, L. Bissett, C. Ciccarelli, Linda M. Delahanty, Veronica Goldman, Olivier J. Hardy, Mary Larkin, Lynne L. Levitsky, R. McEachern, D. Norman, Dennis Chimezie Nwosu, S. Park‐Bennett, D. Richards, Nicole Sherry, Barbara Steiner, Sherida E. Tollefsen, Stefanie Carnes, D. Dempsher, D. Flomo, Timothy J. Whelan, B. Wolff, Ruth S. Weinstock, D. Bowerman, S. Bristol, Jane Bulger, J. Hartsig, Roberto Izquierdo, J. Kearns, R. Saletsky, Paula M. Trief, Philip Zeitler, N. Abramson, A. Bradhurst, N. Celona‐Jacobs, Janine Higgins, Megan M. Kelsey, Georgeanna J. Klingensmith, Kristen J. Nadeau, T. Witten, Kenneth C. Copeland, E. Boss, R Brown, J. Chadwick, Laura Chalmers, Steven D. Chernausek, A. Hebensperger, C. Macha, Rebecca A. Newgent, A. Nordyke, Darin E. Olson, T. Poulsen, Linda Pratt, J. Preske, J. Schanuel, S. Sternlof, Jane Lynch, Nancy Amodei, Rose Ann Barajas, C. Cody, Davis Hale, Joseph Hernandez, Christopher Ibarra, es Pablo Kuri Morales, S. Rivera, G. Rupert, A. Wauters, N. White, Alejandra Arbeláez, D. Flomo, J. Jones, T. Jones, Michelle Sadler, Minna Tanner, A. Timpson, R. Joel Welch, Sonia Caprio, Margaret Grey, Cindy Guandalini, S. Lavietes, Paulina Rose, A. Syme, William V. Tamborlane, Kathryn Hirst, Sharon L. Edelstein, P. Feit, Nisha Grover, Carole Long, Laura Pyle, Barbara Linder, Santica M. Marcovina, Jessica Harting, John Shepherd, Bin Fan, L. Marquez, M. Sherman, J S Brody, Michele Nichols, Elizabeth J. Mayer‐Davis, Yiju Liu, João Lindemberg Bandeira Lima, Samuel S. Gidding, J. Puccella, Erin P. Ricketts, Ronald P. Danis, Amitha Domalpally, Ailsa Goulding, Sean Neill, Pamela Vargo, Denise E. Wilfley, D. Aldrich‐Rasche, Kierra A. Franklin, C. Massmann, Diane M. O’Brien, Judith K. Patterson, Tiffany L. Tibbs, David Van Buren, Mark R. Palmert, R. Ratner, D. Dremaine, Janet Silverstein,

Diabetes and associated disorders

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.