Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome

OBJECTIVE - Evidence suggests that some actions of insulin are effected by inositolphosphoglycan (IPG) mediators. We hypothesize that a deficiency in D-chiro-inositol (DCI) and/or a DCI-containing IPG (DCI-IPG) may contribute to insulin resistance in humans. RESEARCH DESIGN AND METHODS - To assess this possibility in polycystic ovary syndrome (PCOS), we determined insulin sensitivity (Si by frequently sampled intravenous glucose tolerance test), plasma and urinary DCI and myo-inositol (MYO) levels (by gas chromatography/ mass spectrometry), and the release of insulin and DCI-IPG during the oral glucose tolerance test (area under the curve [AUC]) in 23 women with PCOS and 26 normal women. RESULTS - Women with PCOS were heavier than control subjects (P = 0.002 for BMI), but also had decreased S_i (P < 0.001) and increased AUC_insulin (P < 0.001) compared with normal women, even when corrected for BMI. The urinary clearance of DCI (uCl_DCI) was increased almost sixfold in PCOS compared with normal women (P = 0.001), but not MYO clearance (P = 0.10). uCl_DCI correlated inversely with S _i when all women were analyzed together (n = 49, r = -0.50, P < 0.001) and was one of the three best independent parameters predicting S _i. Finally, the ratio of AUC_DCI-IPG to AUC _insulin was decreased threefold in women with PCOS (P < 0.001). CONCLUSIONS- uCl_DCI is inversely correlated with insulin sensitivity in women and is a strong independent predictor of insulin resistance in multivariate models. PCOS, which is characterized by insulin resistance, is associated with a selective increase in uCl_DCI and impaired DCI-IPG release in response to insulin. These findings are consistent with a defect in tissue availability or utilization of DCI in PCOS that may contribute to the insulin resistance of the syndrome.