Over a third of women with polycystic ovarian syndrome (PCOS) display glucose intolerance and multiple risk factors for cardiovascular disease, including central obesity. Interleukin-6, a cytokine that is mainly derived from adipose tissue, has recently been implicated as an important link in the development of cardiovascular disease in obesity. We determined the relations between circulating Interleukin-6 levels and anthropometric, metabolic and hormonal parameters in 38 women with PCOS (mean age: 27plus/minus6 years; mean BMI: 28plus/minus6 kg/m2), along with the effects of short-term Metformin treatment (1500 mg per day) on these variables.
Inteleukin-6 levels in women with PCOS correlated significantly with CRP (r=0.82), BMI (r=0.81) and waist (r=0.76) as well as with indices of insulin sensitivity: FI (r=0.69) and HOMA-R (r=0.60). CRP levels also correlated significantly with BMI (r=0.69) and waist (r=0.63) as well as with indices of insulin sensitivity: FI (r=0.60) and HOMA-R (r=0.48). In multiple regression analysis, the association between Inteleukin-6 and obesity was independent of insulin resistance, with this adipokine being the main determinant of CRP, replacing both obesity and insulin resistance parameters. In a subset of 22 PCOS patients (Obese=11; Lean=11), 6 weeks of metformin therapy produced a significant reduction in weight (80.2 to 78.0 kg; p<0.001), waist (88.7 to 86.3 cm; p=0.015) and CRP (3.7 to 2.5 mg.L-1; p=0.006), but not IL-6 (p=0.62).
In conclusion, IL-6 levels in women with PCOS reflect obesity and independently regulate CRP concentrations. Furthermore, Metformin therapy facilitates early weight loss and reduction of Interleukin-6-regulated CRP, prior to any significant changes in IL-6 levels or insulin resistance. Metformin, by reducing increased C-Reactive Protein concentrations -a marker of low grade chronic inflammation- could have a beneficial effect on reducing the risk for cardiovascular disease and type 2 diabetes. In addition, modulating inflammation may be the mechanism by which Metformin improves PCOS.
24 - 26 Mar 2003
British Endocrine Societies