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

¹ Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
² First Department of Medicine–Endocrine Section, University of Athens Medical School, Athens, Greece
³ Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
⁴ Department of Medicine, Virginia Commonwealth University, Richmond, Virginia
⁵ Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia

Address correspondence and reprint requests to Jean-Patrice Baillargeon, MD, MSc, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. E-mail: jp.baillargeon{at}usherbrooke.ca

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.

Abbreviations: AUC_DCI-PGI, area under the bioactivity curve for DCI-IPG during OGTT • AUC_insulin, area under the insulin curve during OGTT • DCI, D-chiro-inositol • DCI-IPG, DCI-containing inositolphosphoglycan • IPG, inositolphosphoglycan • MYO, myo-inositol • OGTT, oral glucose tolerance test • PCOS, polycystic ovary syndrome • uCl_DCI, urinary clearance of D-chiro-inositol • WHR, waist-to-hip ratio

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