In vitro evidence that hyperglycemia stimulates tumor necrosis factor-a release in obese women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are often insulin resistant and have chronic low-level inflammation. The purpose of this study was to determine the effects of hyperglycemia in vitro on tumor necrosis factor (TNF)-alpha release from motion it clear cells (MNC) in PCOS. Twelve reproductive-age women with PCOS (six lean, six obese) and 12 age-matched controls (six lean, six obese) were studied. Insulin sensitivity (ISHOMA) was estimated from fasting levels of glucose and insulin and percent truncal far was determined by dual energy absorptiometry (DEXA). TNF alpha release was measured from MNC Cultured under euglycemic and hyperglycemic conditions. ISHOMA was higher in obese women with PCOS than in lean women with PCOS (Students t-test; 73.7 +/- 14.8 vs 43.1 +/- 8.6 P < 0.05), but similar to that of obese controls. ISHOMA was positively correlated with percent truncal far (r=0.57, P < 0.04). Obese women with PCOS exhibited all increase in the percent change in TNF alpha release from MNC in response to hyperglycemia compared with obese controls (10 mM, 649 +/- 208% vs 133 +/- 30%, P < 0.003; 15 mM, 799 +/- 347% vs 183 59%, P < 0.04). The TNF alpha response directly correlated with percent truncal far (r=0.45, P < 0.03) and ISHOMA (r=0.40, P < 0.05) for the combined groups, and with plasma testosterone (r=0.60, P < 0.05) for women with PCOS. MNC of obese women with PCOS exhibit all increased TNF alpha response to in vitro physiologic hyperglycemia. MNC-derived TNF alpha release may contribute to insulin resistance and hyperandrogenism, particularly when the combination of PCOS and increased adiposity is present.