Prevention of diabetes with pioglitazone in ACT NOW: Physiologic correlates

Ralph A. DeFronzo, Devjit Tripathy, Dawn C. Schwenke, Mary Ann Banerji, George A. Bray, Thomas A. Buchanan, Stephen C. Clement, Amalia Gastaldelli, Robert R. Henry, Abbas E. Kitabchi, Sunder Mudaliar, Robert E. Ratner, Frankie B. Stentz, Nicolas Musi, Peter D. Reaven

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and were observed for a median of 2.4 years. Indices of insulin sensitivity (Matsuda index [MI]), insulin secretion (IS)/ insulin resistance (IR; ΔI0-120 /ΔG0-120, ΔIS rate [ISR] 0-120/ΔG0-120), and β-cell function (ΔI /ΔG × MI and ΔISR/ΔG × MI) were calculated from plasma glucose, insulin, and C-peptide concentrations during oral glucose tolerance tests at baseline and study end. Diabetes developed in 45 placebo-treated vs. 15 PGZ-treated subjects (odds ratio [OR] 0.28 [95% CI 0.15-0.49]; P < 0.0001); 48% of PGZtreated subjects reverted to normal glucose tolerance (NGT) versus 28% of placebo-treated subjects (P < 0.005). Higher final glucose tolerance status (NGT > IGT > T2DM) was associated with improvements in insulin sensitivity (OR 0.61 [95% CI 0.54- 0.80]), IS (OR 0.61 [95% CI 0.50-0.75]), and β-cell function (ln IS/IR index and ln ISR/IR index) (OR 0.26 [95% CI 0.19-0.37]; all P < 0.0001). Of the factors measured, improved β-cell function was most closely associated with final glucose tolerance status.

Original languageEnglish (US)
Pages (from-to)3920-3926
Number of pages7
JournalDiabetes
Volume62
Issue number11
DOIs
StatePublished - Nov 2013

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    DeFronzo, R. A., Tripathy, D., Schwenke, D. C., Banerji, M. A., Bray, G. A., Buchanan, T. A., Clement, S. C., Gastaldelli, A., Henry, R. R., Kitabchi, A. E., Mudaliar, S., Ratner, R. E., Stentz, F. B., Musi, N., & Reaven, P. D. (2013). Prevention of diabetes with pioglitazone in ACT NOW: Physiologic correlates. Diabetes, 62(11), 3920-3926. https://doi.org/10.2337/db13-0265