Hyperglycemia-induced oxidative stress is independent of excess abdominal adiposity in normal-weight women with polycystic ovary syndrome

Abstract

STUDY QUESTIONWhat is the effect of glucose ingestion on leukocytic reactive oxygen species (ROS) generation in normal-weight women with polycystic ovary syndrome (PCOS) with and without excess abdominal adiposity (AA)?SUMMARY ANSWERNormal-weight women with PCOS exhibit an increase in leukocytic ROS generation in response to glucose ingestion, and this increase is independent of excess AA. WHAT IS KNOWN ALREADYExcess adipose tissue is a source of oxidative stress. Normal-weight women with PCOS exhibit oxidative stress and can have excess AA. STUDY DESIGN AND SIZEThis is a cross-sectional study involving 30 reproductive-age women. PARTICIPANTS/MATERIALS, SETTING AND METHODSFourteen normal-weight women with PCOS (6 normal AA, 8 excess AA) and 16 body composition-matched controls (8 normal AA, 8 excess AA) underwent body composition assessment by dual-energy absorptiometry and an oral glucose tolerance test (OGTT) at a university medical center. Insulin sensitivity was derived from the OGTT (ISOGTT). Blood was drawn while fasting and 2 h after glucose ingestion to measure leukocytic ROS generation and p47 phox protein content and plasma thiobarbituric acid-reactive substances (TBARS) and C-reactive protein (CRP). MAIN RESULTS AND THE ROLE OF CHANCECompared with controls, both PCOS groups exhibited lower ISOGTT (43-54) and greater percentage change ( change) in ROS generation (96-140), p47phox protein (18-28) and TBARS (17-48). Compared with women with PCOS with excess AA, those with normal AA exhibited higher testosterone levels (29) and lower CRP levels (70). For the combined groups, ISOGTT was negatively correlated with the change in ROS generation and p47phox protein. CRP was positively correlated with abdominal fat. The change in p47phox protein was positively correlated with CRP and androgens. LIMITATIONS, REASONS FOR CAUTIONAlthough this study is adequately powered to assess differences in ROS generation between the women with PCOS and control participants, the modest sample size merits caution when interpreting the corroborative results of the additional measures of oxidative stress and inflammation. WIDER IMPLICATIONS OF THE FINDINGSThis study highlights the unique pro-oxidant contribution of circulating leukocytes in the development of insulin resistance and hyperandrogenism in PCOS. STUDY FUNDING/COMPETING INTEREST(S)Supported by NIH grant HD-048535 to F. G. The authors have nothing to disclose. © 2012 The Author.