Endothelial dysfunction and insulin resistance in young women with polycystic ovarian syndrome
To evaluate whether there is a correlation between insulin resistance and nitric oxide-related endothelial dysfunction in patients with polycystic ovarian syndrome (PCOS). Materials and methods: The study was conducted with 25 young women with PCOS and 25 young healthy women, between 18 and 35 years of age. Plasma asymmetric dimethylarginine (ADMA) levels, serum nitric oxide (NO) levels, and homeostatic model assessment of insulin resistance (HOMA-IR) rates were measured in both the patient and control groups. Results: Plasma ADMA levels were significantly higher in PCOS patients than in the controls (P = 0.001). Serum NO levels were significantly lower in patients than in the controls (P = 0.008). The HOMA-IR rates, accepted as an insulin resistance parameter, were significantly higher in patients than in the controls (P = 0.001). Conclusion: Results of the present study indicate that, independent of age, body mass index, and blood lipid profile, there is significant insulin resistance in PCOS patients. However, no correlation was found between HOMA-IR as an insulin resistance determinant and altered ADMA and NO levels. This finding may indicate that there are additional mechanisms of cardiovascular risks in PCOS patients other than insulin resistance.
Endothelial dysfunction and insulin resistance in young women with polycystic ovarian syndrome
To evaluate whether there is a correlation between insulin resistance and nitric oxide-related endothelial dysfunction in patients with polycystic ovarian syndrome (PCOS). Materials and methods: The study was conducted with 25 young women with PCOS and 25 young healthy women, between 18 and 35 years of age. Plasma asymmetric dimethylarginine (ADMA) levels, serum nitric oxide (NO) levels, and homeostatic model assessment of insulin resistance (HOMA-IR) rates were measured in both the patient and control groups. Results: Plasma ADMA levels were significantly higher in PCOS patients than in the controls (P = 0.001). Serum NO levels were significantly lower in patients than in the controls (P = 0.008). The HOMA-IR rates, accepted as an insulin resistance parameter, were significantly higher in patients than in the controls (P = 0.001). Conclusion: Results of the present study indicate that, independent of age, body mass index, and blood lipid profile, there is significant insulin resistance in PCOS patients. However, no correlation was found between HOMA-IR as an insulin resistance determinant and altered ADMA and NO levels. This finding may indicate that there are additional mechanisms of cardiovascular risks in PCOS patients other than insulin resistance.
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- Buyalos RP, Geffner ME, Bersch N, Judd HL, Watanabe RM, Bergman RN, Golde DW. Insulin and insulin-like growth factor-1 responsiveness in polycystic ovarian syndrome. Fertil Steril 1992; 57: 796–803.
- Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000; 20: 2032–2037. 8. Böger RH. The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor. Cardiovasc Res 2003; 59: 824–833.
- Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome. Fertil Steril 2003; 8: 1–25.
- Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001; 5: 62–71.
- Chen BM, Xia LW, Zhao RQ. Determination of NC,NG- dimethylarginine in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997; 692: 467–471.
- Sorensen MB, Franks S, Robertson C, Pennell DJ, Collins P. Severe endothelial dysfunction in young women with polycystic ovary syndrome is only partially explained by known cardiovascular risk factors. Clin Endocrinol 2006; 65: 655–659.
- Pamuk BO, Torun AN, Kulaksizoglu M, Ertugrul D, Ciftci O, Kulaksizoglu S, Yildirim E, Demirag NG. Asymmetric dimethylarginine levels and carotid intima-media thickness in obese patients with polycystic ovary syndrome and their relationship to metabolic parameters. Fertil Steril 2010; 93: 1227–1233.
- Depres JP, Lamarche M, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952–957.
- Kravariti M, Naka KK, Kalantaridou SN, Kazakos N, Katsouras CS, Makrigiannakis A, Paraskevaidis AE, Chrousos GP, Tsatsoulis A, Michalis LK. Predictors of endothelial dysfunction in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 5088–5095.
- Caballero AE. Endothelial dysfunction in obesity and ınsulin resistance: a road to diabetes and heart disease. Obes Res 2003; 11: 1278–1289.
- Mather KJ, Verma S, Corenblum B, Anderson TJ. Normal endothelial function despite insulin resistance in healthy women with the polycystic ovary syndrome. J Clin Endocrinol Metab 2000; 85: 1851–1856.
- Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron A. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 2001; 103: 1410– 1415.
- Orio F, Palomba S, Spinelli L, Cascella T, De Simone B, Di Biase S, Russo T, Labella D, Zullo F, Lombardi G et al. Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89: 4588–4593.
- Boger RH, Bode-Boger SM, Thiele W, Junker W, Alexander K, Frolich JC. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1997; 95: 2068–2074.
- Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, Imaizumi T. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99: 1141– 1146.
- Toulis KA, Goulis DG, Mintziori G, Kintiraki E, Eukarpidis E, Mouratoglou SA, Pavlaki A, Stergianos S, Poulasouchidou M, Tzellos TG et al. Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum Reprod Update 2011; 17: 741–760.
- Moran LJ, Cameron JD, Strauss BJ, Teede HJ. Vascular function in the diagnostic categories of polycystic ovary syndrome. Hum Reprod 2011; 26: 2192–2199.
- Choi YS, Yang HI, Cho S, Jung JA, Jeon YE, Kim HY, Seo SK, Lee BS. Serum asymmetric dimethylarginine, apelin, and tumor necrosis factor-α levels in non-obese women with polycystic ovary syndrome. Steroids 2012; 77: 1352–1358.
- Ngo DT, Chan WP, Rajendran S, Heresztyn T, Amarasekera A, Sverdlov AL, O’Loughlin PD, Morris HA, Chirkov YY, Norman RJ et al. Determinants of insulin responsiveness in young women: impact of polycystic ovarian syndrome, nitric oxide, and vitamin D. Nitric Oxide 2011; 25: 326–330.
- Fard A, Tuck C, Donis J, Sciacca R, DiTullio M, Wu H, Bryant T, Chen N, Torres Tamayo M, Ramasamy R et al. Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 2000; 20: 2039–2044.
- Ito A, Tsao PS, Adimoolam S, Kimoto M, Ogawa T, Cooke JP. Novel mechanism for endothelial dysfunction: dysregulation of dimethylarginine dimethylaminohydrolase. Circulation 1999; 99: 3092–3095.
- Chan JR, Boger RH, Bode-Boger SM, Tanqphao O, Tsao PS, Blaschke TF, Cooke JP. Asymmetric dimethylarginine increases mononuclear cell adhesiveness in hypercholesterolemic humans. Arterioscler Thromb Vasc Biol 2000; 20: 1040–1046.