The Relationship Between Growth Differentiation Factor-15 And Insulin Resistance In Patients With Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome(PCOS)is a common endocrine disorder in women of reproductive age.The aetiology of PCOS is underpinned by both insulin resistance and hyperandrogenism,with insulin resistance exacerbating hyperandrogenism,leading to menstrual dysfunction and clinical manifestations of hyperandrogenemia in PCOS patients.Growth differentiation factor-15(GDF-15)provides an endocrine signal of nutritional stress.Previous study have showed that GDF-15 is closely related to insulin resistance.However,the relationship between GDF-15 and insulin resistance and clinical manifestations in PCOS patients has not been fully studied.Methods: We included 148 PCOS patients and 52 controls matched for age and BMI from Tongji hospital.According to the diagnostic criteria of metabolic syndrome(MS)proposed by the International Diabetes Federation in 2005,PCOS and control subjects were divided into MS group and non-MS group,respectively.Serum GDF-15 levels,glucose-related variables and free testosterone were measured in all subjects.Results: PCOS patients exhibited hyperinsulinism,hyperandrogenism,and dyslipidemia,as well as elevated LH levels compared to controls.Serum GDF-15 levels were increased in patients with PCOS compared with control subjects(220.16 ± 62.02 vs 300.67 ± 84.11pg/ml,P < 0.001).Notably,levels of GDF-15 remained increased in MS(-)PCOS compared to matched controls(204.28 ± 51.07 vs 288.49 ± 82.72 pg/ml,P < 0.001).GDF-15 levels positively correlated with HOMA-IR(partial r = 0.224,P = 0.024);inversely correlated with QUICKI(partial r =-0.233,P = 0.019,ISIG(partial r =-0.242,P = 0.015)and ISIM(partial r =-0.232,P = 0.020)after controlling for age,TG,CRP,BMI,waist circumference,free testosterone and menstrual frequencies.The receiver operating characteristic curve(ROC)showed that GDF-15 could be used as a prediction factor of PCOS with high sensitivity and specificity.Conclusions: Circulating GDF-15 levels are increased in PCOS patients and associated with insulin resistance,hyperandrogenemia and menstrual disorders.