Altered D-Chiro-Inositol Urinary Clearance in Women With Polycystic Ovary Syndrome

Abstract

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 (S_i 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.