Increased fetuin-B levels are associated with carotid intima media thickness and hormonal-metabolic disturbances in women with polycystic ovary syndrome

Yıl 2020, Cilt: 51 Sayı: 2, 106 - 112, 15.06.2020

Aslı Bayındır , Gokcen Unal , Cetin İmamoğlu , Yasemin Alan

https://doi.org/10.16948/zktipb.679178

Cited By: 1

Öz

Objective: Fetuin-B is a novel peptide hormone involves in energy metabolism, atherosclerosis and reproductive system. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder associated with increased cardiovascular risk factors. We aimed to ascertain whether circulating fetuin-B levels were altered in women with PCOS and whether there was any association between fetuin-B and hormonal-metabolic parameters as well as carotid intima media thickness (CIMT).
Material and Methods: Eighty women with PCOS and 80 age- and BMI-matched controls without PCOS were recruited to this cross-sectional study. Circulating fetuin-B levels were measured by ELISA. Metabolic- hormonal parameters and CIMT of recruited subjects were also determined.
Results: Circulating fetuin-B levels were significantly elevated in women with PCOS compared to controls (409.54 ± 32.51 vs. 325.53 ± 26.86 ng/ml, P<0.001). PCOS subjects with insulin resistance showed significantly elevated circulating fetuin-B levels compared to those PCOS subjects without insulin resistance (416.03 ± 30.41 vs. 399.27 ± 33.56 ng/ml, P = 0.024). Overweight/obese women had significantly higher circulating fetuin-B levels than lean subjects in PCOS groups (416.32 ± 30.99 vs. 400.82 ± 32.77 ng/ml, P = 0.033). Fetuin-B levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free-androgen index (FAI), high sensitivity C-reactive protein (hs-CRP), triglycerides and CIMT in PCOS subjects whereas fetuin-B negatively correlated with high density lipoprotein cholesterol (HDL-C). Moreover, binary logistic regression analysis revealed that the risk of having PCOS was increased in parallel with elevation of fetuin-B levels.
Conclusion: Circulating fetuin-B levels were significantly increased in PCOS subjects and fetuin-B levels were closely related to cardiovascular risk and hormonal-metabolic disturbances in women with PCOS.

ÖZET
Amaç :Fetuin-b enerji metabolizması, ateroskleroz ve üreme sisteminde rol oynayan yeni bir peptid hormonudur.Polikistik over sendromu (PKOS) üreme ve metabolik sistemleri içeren artmış kardivasküler risk taşıyan bir hastalıktır.Bu çalışmada PKOS'lu kadınlarda dolaşımdaki Fetuin-b düzeyinde değişiklik olup olmadığını ve Fetuin-b düzeyi ile hormonal-metabolik parametreler ile Karotis intima media kalınlığı (CIMT) arasında bir ilişki olup olmadığını tespit etmeyi amaçladık.
Gereç ve Yöntemler:Kesitsel çalışmamıza 80 PKOS’lu kadın alınmıştır. Kontrol grup olarak 80 tane yaş ve BMI uyumlu kadın çalışmaya alınmıştır.Dolaşımdaki Fetuin-b seviyeleri ELISA yöntemi ile ölçüldü. Ayrıca deneklerin metabolik hormonal parametreleri ve CIMT'si de belirlenmiştir.
Bulgular:Dolaşımdaki Fetuin-b düzeyleri PKOS'lu kadınlarda kontrollere göre anlamlı derecede yüksek bulundu (409.54 ± 32.51 vs. 325.53 ± 26.86 ng/ml, P<0.001).İnsülin direncine sahip PKOS denekleri, insülin direncine sahip olmayan PCOS öznelerine göre anlamlı derecede yüksek dolaşım Fetuin-B seviyeleri gösterdi (416.03 ± 30.41 vs. 399.27 ± 33.56 ng/ml, P = 0.024).
Aşırı kilolu / obez kadınlarda PKOS gruplarında düşük kilolu deneklerden anlamlı derecede daha yüksek dolaşımdaki Fetuin-b düzeyleri vardı (416.32 ± 30.99 vs. 400.82 ± 32.77 ng/ml, P = 0.033).Fetuin-B düzeyleri BKİ, insülin direncinin homeostaz modelinin değerlendirilmesi (HOMA-IR), free-androgen index (FAI), high sensitivity C-reactive protein (hs-CRP) trigliseritler ve CIMT ile pozitif korelasyon gösterir iken yüksek yoğunluklu lipoprotein kolesterol (HDL-C) ile negatif korelasyon göstermektedir. Ayrıca ikili lojistik regresyon analizi, PKOS olma riskinin Fetuin-B seviyelerinin yükselmesine paralel olarak arttığını ortaya koydu.
Sonuç:Dolaşımdaki Fetuin-B düzeyleri PKOS'lu hastalarda anlamlı olarak artmış olup Fetuin-B düzeyleri PKOS'lu kadınlarda kardiyovasküler risk ve hormonal metabolik bozukluklarla yakından ilişkilidir.

Anahtar Kelimeler

Polycystic ovary syndrome, fetuin-B, insulin resistance, body mass index, carotid intima media thickness

Kaynakça

• References 1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab [Internet]. 2004 Jun [cited 2014 Mar 2];89(6):2745–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15181052 2. Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod [Internet]. 2013 Mar 1;28(3):777–84. Available from: http://humrep.oxfordjournals.org/lookup/doi/10.1093/humrep/des463
• 3. Hoffman LK, Ehrmann DA. Cardiometabolic features of polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab [Internet]. 2008 Apr [cited 2014 Aug 9];4(4):215–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18250636 4. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7(4):219–31. 5. Meex RC, Hoy AJ, Morris A, Brown RD, Lo JCY, Burke M, et al. Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism. Cell Metab [Internet]. 2015 Dec;22(6):1078–89. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1550413115004805 6. Olivier E, Soury E, Ruminy P, Husson A, Parmantier F, Daveaum, et al. Fetuin-B, a second member of the fetuin family in mammals. Biochem J [Internet]. 2000 Sep 1;350(2):589–97. Available from: http://www.biochemj.org/cgi/doi/10.1042/bj3500589 7. Li Z, Lin M, Liu C, Wang D, Shi X, Chen Z, et al. Fetuin-B links nonalcoholic fatty liver disease to type 2 diabetes via inducing insulin resistance: Association and path analyses. Cytokine [Internet]. 2018 Aug;108:145–50. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043466618301091 8. Kralisch S, Hoffmann A, Lössner U, Kratzsch J, Blüher M, Stumvoll M, et al. Regulation of the novel adipokines/ hepatokines fetuin A and fetuin B in gestational diabetes mellitus. Metabolism [Internet]. 2017;68:88–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28183456 9. Zhu K, Wang Y, Shu P, Zhou Q, Zhu J, Zhou W, et al. Increased serum levels of fetuin B in patients with coronary artery disease. Endocrine [Internet]. 2017 Oct;58(1):97–105. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28822077 10. Jung SH, Won K-J, Lee KP, Kim H-J, Seo E-H, Lee HM, et al. The serum protein fetuin-B is involved in the development of acute myocardial infarction. Clin Sci [Internet]. 2015 Jul 1;129(1):27–38. Available from: http://www.clinsci.org/cgi/doi/10.1042/CS20140462 11. Dietzel E, Floehr J, Van de Leur E, Weiskirchen R, Jahnen-Dechent W. Recombinant fetuin-B protein maintains high fertilization rate in cumulus cell-free mouse oocytes. Mol Hum Reprod [Internet]. 2017;23(1):25–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27733489 12. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod [Internet]. 2004 Jan 1;19(1):41–7. Available from: http://humrep.oxfordjournals.org/lookup/doi/10.1093/humrep/deh098 13. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab [Internet]. 1961 Nov [cited 2014 Jun 18];21:1440–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13892577 14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia [Internet]. 1985 Jul [cited 2014 Jul 13];28(7):412–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3899825 15. Sidhu PS, Desai SR. A simple and reproducible method for assessing intimal-medial thickness of the common carotid artery. Br J Radiol. 1997;70(JAN.):85–9. 16. Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods [Internet]. 2007 May;39(2):175–91. Available from: http://www.springerlink.com/index/10.3758/BF03193146 17. Geloneze B, Repetto EM, Geloneze SR, Tambascia MA, Ermetice MN. The threshold value for insulin resistance (HOMA-IR) in an admixtured population. Diabetes Res Clin Pract [Internet]. 2006 May;72(2):219–20. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0168822705004213 18. Adamska A, Polak AM, Krentowska A, Łebkowska A, Hryniewicka J, Leśniewska M, et al. Increased serum fetuin-B concentration is associated with HOMA-β and indices of liver steatosis in women with polycystic ovary syndrome: a pilot study. Endocr Connect [Internet]. 2019 Jul 1; Available from: http://www.ncbi.nlm.nih.gov/pubmed/31307012 19. Fang L, Hu X, Cui L, Lv P, Ma X, Ye Y. Serum and follicular fluid fetuin-B levels are correlated with fertilization rates in conventional IVF cycles. J Assist Reprod Genet [Internet]. 2019 Jun;36(6):1101–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31073723 20. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(6):2562–8. 21. Aziz M, Sidelmann JJ, Faber J, Wissing M-LM, Naver K V, Mikkelsen A-L, et al. Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes. Acta Obstet Gynecol Scand [Internet]. 2015 Oct;94(10):1082–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26123797 22. Toulis KA, Goulis DG, Mintziori G, Kintiraki E, Eukarpidis E, Mouratoglou S-A, et al. Meta-analysis of cardiovascular disease risk markers in women with polycystic ovary syndrome. Hum Reprod Update [Internet]. 2011 Nov 1;17(6):741–60. Available from: http://humupd.oxfordjournals.org/cgi/doi/10.1093/humupd/dmr025 23. Polak JF, Szklo M, Kronmal RA, Burke GL, Shea S, Zavodni AEH, et al. The Value of Carotid Artery Plaque and Intima-Media Thickness for Incident Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc [Internet]. 2013 Apr 8;2(2):e000087–e000087. Available from: http://jaha.ahajournals.org/cgi/doi/10.1161/JAHA.113.000087 24. Li Z, He C, Liu Y, Wang D, Lin M, Liu C, et al. Association of Fetuin-B with Subclinical Atherosclerosis in Obese Chinese Adults. J Atheroscler Thromb [Internet]. 2019; Available from: https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_49619/_article