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
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, 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
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.
Trial registration: ClinicalTrials.gov NCT00081328.
© 2018 by the American Diabetes Association.
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Source: PubMed