Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D

► Polycystic ovarian syndrome (PCOS) is associated with endothelial dysfunction and platelet NO resistance. ► However, PCOS is also associated with insulin resistance (IR) and obesity. ► In these young PCOS subjects and controls, platelet NO resistance and low plasma vitamin D levels correlated with...

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Published in:Nitric oxide 2011-10, Vol.25 (3), p.326-330
Main Authors: Ngo, D.T.M., Chan, W.P., Rajendran, S., Heresztyn, T., Amarasekera, A., Sverdlov, A.L., O’Loughlin, P.D., Morris, H.A., Chirkov, Y.Y., Norman, R.J., Horowitz, J.D.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Asymmetric dimethylarginine
Female
Humans
Insulin - metabolism
Insulin Resistance
Middle Aged
Nitric Oxide - metabolism
Obesity
Polycystic ovary syndrome
Polycystic Ovary Syndrome - metabolism
Vitamin D
Vitamin D - metabolism
Women health
Young Adult
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Summary:► Polycystic ovarian syndrome (PCOS) is associated with endothelial dysfunction and platelet NO resistance. ► However, PCOS is also associated with insulin resistance (IR) and obesity. ► In these young PCOS subjects and controls, platelet NO resistance and low plasma vitamin D levels correlated with IR. ► However, in PCOS subjects only, high BMI, elevated CRP and elevation of ADMA concentrations were correlates of IR. ► These differential relationships may contribute to incremental atherogenic risk in PCOS. Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects; this may contribute to the increased cardiovascular risk associated with this syndrome.
ISSN:1089-8603
1089-8611
DOI:10.1016/j.niox.2011.06.005