CLINICAL STUDY Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome Flavia Tosi, Romolo Dorizzi, Roberto Castello, Claudio Maffeis, Giovanna Spiazzi, Giacomo Zoppini, Michele Muggeo and Paolo Moghetti Endocrinology and Metabolism, Department of Biomedical and Surgical Sciences, Universityof Verona, 37126 Verona, Italy (Correspondence should be addressed to P Moghetti; Email: paolo.moghetti@univr.it) Abstract Objective: Increased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association. Design and methods: Serum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6G4.2 years, body mass index (BMI) 23.6G3.5 kg/m 2 ), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance. Results: Hs-CRP concentrations were higher in PCOS women (3.43G2.01 mg/l) than in HA subjects and healthy women (2.43G1.04, P!0.005; and 2.75G0.86 mg/l, P!0.05 respectively versus PCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable. Conclusions: PCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association. European Journal of Endocrinology 161 737–745 Introduction A number of studies indicate that serum high-sensitivity C-reactive protein (hs-CRP) is a novel independent cardiovascular risk factor (1). This protein, synthesized by the liver, is a sensitive and stable marker of low-grade chronic inflammation, a key process in the pathogenesis of atherosclerosis (2). Hs-CRP serum concentration, even within the normal range, independently predicted myocardial infarction and ischemic stroke in subjects of the general population – either with or without classical cardiovascular risk factors – as well as in patients with cardiovascular disease (3–5). More recently, hs-CRP levels have also been linked to insulin resistance and the associated features (6, 7). In the general population, hs-CRP levels increase as a function of the number of metabolic alterations and are associated with the metabolic syndrome, a cluster of metabolic disorders that increases the risk of atherosclerosis (8). In addition, large prospective studies showed that hs-CRP indepen- dently predicted risk for type 2 diabetes (9, 10). Some previous studies assessed serum hs-CRP levels in young women with polycystic ovary syndrome (PCOS), a clinical disorder characterized by hyperandrogenism and ovarian dysfunction. Many of these women show a cluster of cardiovascular risk factors, such as obesity, insulin resistance, lipid abnormalities, hypertension, and abnormal glucose tolerance (11), suggesting that they may have an increased cardiovascular risk later in life. Several of these studies showed higher levels of serum hs-CRP in PCOS women, as compared with controls (12–20). However, this finding was not confirmed by other studies (21–25). The reasons for these discrepan- cies are not readily understood. Most studies carried out in PCOS women examined obese subjects and reported a relationship between hs-CRP levels and body weight (13, 16, 22, 26). As hs-CRP production in the liver is modulated by some European Journal of Endocrinology (2009) 161 737–745 ISSN 0804-4643 q 2009 European Society of Endocrinology DOI: 10.1530/EJE-09-0379 Online version via www.eje-online.org Downloaded from Bioscientifica.com at 05/26/2020 10:43:25AM via free access