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Pediatr Diabetes. 2012 Aug;13(5):376-83. doi: 10.1111/j.1399-5448.2011.00841.x. Epub 2012 Feb 15.

Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study.

Collaborators (225)

McKay S, Anderson B, Bush C, Gunn S, Haymond M, Holden H, Hwu K, Jones S, McGirk, Schreiner B, Thamotharan S, Zarate M, Cuttler L, Abrams E, Casey T, Dahms W, Davis A, Haider A, Huestis S, Ievers-Landis C, Kaminski B, Koontz M, MacLeish S, McGuigan P, Narasimhan S, Rogers D, Geffner M, Barraza V, Chang N, Conrad B, Dreimane D, Estrada S, Fisher L, Fleury-Milfort E, Hernandez S, Hollen B, Kaufman F, Law E, Mansilla V, Miller D, Muñoz C, Ortiz R, Sanchez J, Ward A, Wexler K, Xu YK, Yasuda P, Levitt Katz L, Berkowitz R, Gralewski K, Johnson B, Kaplan J, Keating C, Lassiter C, Lipman T, McGinley G, McKnight H, Schwartzman B, Willi S, Arslanian S, Bacha F, Foster S, Galvin B, Hannon T, Kriska A, Libman I, Marcus M, Porter K, Songer T, Venditti R, Goland R, Cain R, Fennoy I, Gallagher D, Kringas P, Leibel N, Motaghedi R, Ng D, Ovalles M, Pellizzari M, Rapaport R, Robbins K, Seidman D, Siegel-Czarkowski L, Speiser P, Laffel L, Goebel-Fabbri A, Hall M, Higgins M, Malloy M, Milaszewski K, Orkin L, Rodriguez-Ventura A, Nathan D, Bissett L, Blumenthal K, Delahanty L, Goldman V, Goseco A, Larkin M, Levitsky L, McEachern R, Milaszewski K, Norman D, Nwosu B, Park-Bennett S, Richards D, Sherry N, Steiner B, Tollefsen S, Carnes S, Dempsher D, Flomo D, Kociela V, Whelan T, Wolff B, Weinstock R, Bowerman D, Bristol S, Bulger J, Hartsig J, Izquierdo R, Kearns J, Saletsky R, Trief P, Zeitler P, Abramson N, Bradhurst A, Celona-Jacobs N, Higgins J, Hull A, Kelsey M, Klingensmith G, Nadeau K, Witten T, Copeland K, Boss E, Brown R, Chadwick J, Chalmers L, Chernausek S, Macha C, Newgent R, Nordyke A, Olson D, Poulsen T, Pratt L, Preske J, Schanuel J, Smith J, Sternlof S, Lynch J, Amodei N, Barajas R, Swisher R, Cody C, Hale D, Hernandez J, Ibarra C, Morales E, Rivera S, Rupert G, Wauters A, White N, Arbeláez A, Jones J, Jones T, Sadler M, Tanner M, Timpson A, Welch R, Caprio S, Grey M, Guandalini C, Lavietes S, Mignosa M, Rose P, Syme A, Tamborlane W, Edelstein S, Feit P, Grover N, Long C, Pyle L, Linder B, Marcovina S, Chmielewski J, Ramirez M, Strylewicz G, Shepherd J, Fan B, Marquez L, Sherman M, Wang J, Mayer-Davis E, Liu Y, Nichols M, Wilfley D, Aldrich-Rasche D, Franklin K, Laughlin D, Leibach G, Massmann C, Mills M, O'Brien D, Patterson J, Tibbs T, Van Buren D, Vannucci A, Zhang P, Palmert M, Epstein L, Silverstein J, Bacha F, Pyle L, Nadeau K, Cuttler L, Goland R, Haymond M, Levitsky L, Lynch J, Weinstock RS, White NH, Caprio S, Arslanian S.

Author information

1
Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.

Abstract

OBJECTIVE:

To investigate insulin sensitivity and secretion indices and determinants of glycemic control in youth with recent-onset type 2 diabetes (T2DM) at randomization in the TODAY study, the largest study of youth with T2DM to date.

METHODS:

We examined estimates of insulin sensitivity [1/fasting insulin (1/I(F)), fasting glucose/insulin (G(F) /I(F)), 1/fasting C-peptide (1/C(F)), G(F) /C(F)], β-cell function [insulinogenic index (ΔI30/ΔG30), and ΔC30/ΔG30], and disposition index (DI) in the TODAY cohort of 704 youth (14.0 ± 2.0 yr; diabetes duration 7.8 ± 5.8 months; 64.9% female; 41.1% Hispanic, 31.5% Black, 19.6% White, 6.1% American Indian, and 1.7% Asian) according to hemoglobin A1c (HbA1c) quartiles at study randomization. The randomization visit followed a run-in period (median 71 d) during which glycemic control (HbA1c ≤ 8% for at least 2 months) was achieved with metformin alone. These measures were also examined in relation to screening HbA1c levels before run-in.

RESULTS:

Insulin secretion indices declined with increasing HbA1c quartiles, at randomization (ΔC30/ΔG30: 0.11 ± 0.09, 0.10 ± 0.19, 0.07 ± 0.06, and 0.03 ± 0.03 ng/mL per mg/dL, p < 0.0001; DI: 0.03 ± 0.03, 0.03 ± 0.05, 0.02 ± 0.02, and 0.01 ± 0.01 mg/dL(-1) , p < 0.0001) and at screening, with no significant difference in insulin sensitivity. There were no significant differences in estimates of insulin sensitivity or secretion between genders or across the different racial groups. At randomization and screening, HbA1c correlated with DI (r = -0.3, p < 0.001), with ΔC30/ΔG30, but not with insulin sensitivity estimates.

CONCLUSIONS:

In youth with recent-onset T2DM treated with metformin, glycemic control, as measured by HbA1c, appears to be associated with residual β-cell function and not insulin sensitivity.

PMID:
22332798
PMCID:
PMC3355206
DOI:
10.1111/j.1399-5448.2011.00841.x
[Indexed for MEDLINE]
Free PMC Article

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