Brief report Effect of pioglitazone on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance Manuel Gonza ´lez-Ortiz * , Eduardo Herna ´ndez-Salazar, Ange ´lica M. Kam-Ramos, Esperanza Martı ´nez-Abundis Medical Research Unit in Clinical Epidemiology, Hospital of Specialties, Medical Unit of High Specialty, West National Medical Center, Mexican Institute of Social Security, Guadalajara, Mexico Received 18 February 2006; accepted 10 May 2006 Available online 15 June 2006 Abstract Aim: To evaluate the effect of a thiazolidinedione, pioglitazone, on insulin secretion in patients with both impaired fasting glucose and impaired glucose tolerance. Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out in 18 overweight or obese patients with both impaired fasting glucose and impaired glucose tolerance. Pharmacological intervention consisted of an oral morning administration of pioglitazone (30 mg) or a placebo with a similar presentation for 30 days. Before and after the intervention, glucose, creatinine, lipid profile and uric acid concentrations were measured. To evaluate insulin secretion (early, late and total phases) and insulin sensitivity, a hyperglycemic-hyperinsulinemic clamp was also performed. Results: There were significant reductions ( p = 0.008) in fasting insulin concentration (121 versus 45 pmol/l), late (565 versus 307 pmol/l) and total insulin secretion (474 versus 254 pmol/l), as well as, in 2 h postload glucose levels (9.7 versus 6.9 mmol/l, p = 0.028), with an increment in insulin sensitivity after pioglitazone administration (7.5 versus 9.9). Conclusion: Pioglitazone administration during a period of 4 weeks decreased late and total insulin secretion phases, fasting insulin and 2 h postload glucose levels, and improved insulin sensitivity in patients with both impaired fasting glucose and impaired glucose tolerance. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Pioglitazone; Insulin secretion; Insulin sensitivity; Impaired fasting glucose; Impaired glucose tolerance 1. Introduction Early stages of glucose dysregulation such as impaired fasting glucose and impaired glucose toler- ance have been identified as risk factors that predict the future onset of type 2 diabetes [1]. Insulin resistance is central to the pathogenesis and is initially compensated by an increased insulin secretion; over time, insulin secretion progressively fails and diabetes appears [2]. Thiazolidinediones are synthetic peroxisome pro- liferator-activated receptor-gamma (PPAR-gamma) agonists that regulate several cellular functions decreas- ing insulin resistance. Emerging unclear evidence such as in vitro and in some in vivo studies suggest that www.elsevier.com/locate/diabres Diabetes Research and Clinical Practice 75 (2007) 115–118 * Corresponding author at: Montes Urales 1409, Colonia Indepen- dencia, 44340, Guadalajara, Mexico. Tel.: +52 33 38267022; fax: +52 33 36161218. E-mail address: uiec@prodigy.net.mx (M. Gonza ´lez-Ortiz). 0168-8227/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2006.05.003