Circulating irisin and glucose-dependent insulinotropic peptide are associated with the development of polycystic ovary syndrome

Context: Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, and/or hyperandrogenism. In addition, many PCOS patients present with dyslipidemia, insulin resistance, and obesity. Due to the complexity of this disorder, the causes of PCOS remain to be identified. Objectives: Because many PCOS patients have a propensity to develop dyslipidemia, we hypothesized that the brown adipose-differentiation factor, irisin, and the glucose-dependent insulinotropic peptide (GIP) play a role in the development of PCOS. Design and Setting: Serum hormone levels in 202 PCOS patients and 47 healthy women were investigated. Patients or Other Participants: Patients were stratified based on the presence/absence of metabolic syndrome risk factors, as defined by the National Cholesterol Education Program's Adult Treatment Panel III report (ATPIII [+] and ATPIII [-]), or body mass index (healthy-weight and overweight). Main Outcome Measures: We measured serum irisin, GIP, LH, anti-Mullerian hormone (AMH), and androgens as well as metabolic indices including homeostasis model assessment-insulin resistance, Matsuda's sensitivity index, and quantitative insulin-sensitivity check index. Results: PCOS patients exhibited hyperandrogenism, dyslipidemia, and hyperinsulinism, as well as elevated LH and AMH levels. In addition, fasting irisin level (P < .001) and glucose-induced GIP response (P = .013) in PCOS patients were significantly elevated as compared to those of control women. Remarkably, levels of fasting irisin and glucose-induced GIP response remained significantly elevated in ATP III [-] PCOS and healthy-weight PCOS patients when compared to matched controls. Analysis of the effect size indicated that both fasting irisin and glucose-induced GIP response are significant risk factors for PCOS with odds ratios of 6.63 and 4.21, respectively. Conclusion: Although there is as yet no evidence for a causal link between irisin and/or GIP and PCOS, it is conceivable that irisin and GIP might contribute to the development of PCOS and may also represent novel PCOS biomarkers.