An open pilot study to evaluate the effects of metformin and life style changes on serum paraoxonase activity and oxidative stress markers in premenopausal, obese, insulin resistant women

Abstract

Background: The prevention of type 2 diabetes has great clinical importance. Many pharmacologic and nonpharmacologic methods arc used to prevent type 2 DM. Metformin reduces the risk of developing diabetes in insulin resistant subjects. Oxidative stress plays pivotal roles in the pathogenesis and complications of diabetes mellitus. Paraoxonase 1 has antioxidant capacity. Objective: This study was planned to assess the effects of metformin and life style changes on paraoxonase activity and oxidative stress markers in premenopausal, obese, insulin resistant women. Design.Open-pilot clinical study. Subjects and methods: Thirty-two insulin resistant, premenopausal, obese women were enrolled into this clinical study. These women were treated by diet + exercise + metformin (1700 mg/d) for 6-month interval. All anthropometric characteristics, serum fasting and postprandial glucose, fasting insulin, paraoxonase, arylesterase, and malondialdehyde (MDA) levels and lipid sub-fractions were measured at the commencement and the finish of the study. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Results: Significantly reduced body weight, body mass index, waist circumference measurements, HOMA-IR and serum fasting insulin, postprandial glucose, triglyceride, MDA levels and paraoxonase/high density lipoprotein cholesterol (HDL-C) ratio were observed at the end of the study compared with initial evaluations. Conversely, there were considerable increases in scrum arylesterase and HDL-C levels following the treatment. Nevertheless, the increase in serum PON-1 level was statistically insignificant. Arylesterase was inversely correlated with TC, LDL-C levels and HOMA-IR. Conclusions: Metformin treatment with intensive life-style modification may be appropriate management in premenopausal, obese, insulin resistant women who have increased propensity for the development of type 2 diabetes, although long-term, controlled studies are needed for evaluation in greater detail.