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.


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 Si (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 Si when all women were analyzed together (n = 49, r = -0.50, P < 0.001) and was one of the three best independent parameters predicting Si. 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.
Baillargeon
Jean-Patrice
JP
Department of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. jp.baillargeon@usherbrooke.ca
Diamanti-Kandarakis
Evanthia
E
Ostlund
Richard E
RE
Apridonidze
Teimuraz
T
Iuorno
Maria J
MJ
Nestler
John E
JE
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure; D015992:Body Mass Index; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007294:Inositol / Q000097:blood / Q000652:urine*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D016015:Logistic Models; D015999:Multivariate Analysis; D011085:Polycystic Ovary Syndrome / Q000378:metabolism* / Q000503:physiopathology; D013739:Testosterone / Q000097:blood; D049629:Waist-Hip Ratio
D007328:Insulin; D013739:Testosterone; D007294:Inositol