Citation: Journal of Clinical Endocrinology & Metabolism. 101(5):2056-62, 2016 May.Journal: The Journal of clinical endocrinology and metabolism.Published: 2016ISSN: 0021-972X.Full author list: Tripathy D; Schwenke DC; Banerji M; Bray GA; Buchanan TA; Clement SC; Henry RR; Kitabchi AE; Mudaliar S; Ratner RE; Stentz FB; Musi N; Reaven PD; DeFronzo RA.UI/PMID: 26982008.Subject(s): *Blood Glucose/an [Analysis] | Diabetes Mellitus, Type 2/bl [Blood] | *Diabetes Mellitus, Type 2/ci [Chemically Induced] | Diabetes Mellitus, Type 2/ep [Epidemiology] | Diabetes Mellitus, Type 2/pc [Prevention & Control] | Female | Humans | *Hypoglycemic Agents/ae [Adverse Effects] | Incidence | Insulin/bl [Blood] | Insulin Resistance/ph [Physiology] | Male | Middle Aged | *Substance Withdrawal Syndrome/ep [Epidemiology] | *Thiazolidinediones/ae [Adverse Effects]Institution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1210/jc.2015-4202 (Click here)Abbreviated citation: J Clin Endocrinol Metab. 101(5):2056-62, 2016 May.Local Holdings: Available online through MWHC library: 1999- June 2013, Available in print through MWHC library: 1999 - 2006.Abstract: CONTEXT: Thiazolidinediones have proven efficacy in preventing diabetes in high-risk individuals. However, the effect of thiazolidinediones on glucose tolerance after cessation of therapy is unclear.Abstract: OBJECTIVE: To examine the effect of pioglitazone (PIO) on incidence of diabetes after discontinuing therapy in ACT NOW. Design, Settings and Patients: Two-hundred ninety-three subjects (placebo [PLAC], n = 138; PIO, n = 152) completed a median followup of 11.7 mo after study medication was stopped.Abstract: RESULTS: Diabetes developed in 138 (12.3%) of PLAC vs 17 of 152 PIO patients (11.2%; P = not significant, PIO vs PLAC). However, the cumulative incidence of diabetes from start of study medication to end of washout period remained significantly lower in PIO vs PLAC (10.7 vs 22.3%; P < .005). After therapy was discontinued, 23.0% (35/152) of PIO-treated patients remained normal-glucose tolerant (NGT) vs 13.8% (19/138) of PLAC-treated patients (P = .04). Insulin secretion/insulin resistance index (I0-120/G0-120 x Matsuda index) was markedly lower in subjects with impaired glucose tolerance (IGT) who converted to diabetes during followup vs those who remained IGT or NGT. The decline in-cell function (insulin secretion/insulin resistance index) was similar in subjects with IGT who developed diabetes, irrespective of whether they were treated with PIO or PLAC.Abstract: CONCLUSIONS: 1) The protective effect of PIO on incidence of diabetes attenuates after discontinuation of therapy, 2) cumulative incidence of diabetes in individuals exposed to PIO remained significantly (56%) lower than PLAC and a greater number of PIO-treated individuals maintained NGT after median followup of 11.4 mo, and 3) low insulin secretion/insulin resistance index is a strong predictor of future diabetes following PIO discontinuation.