title: Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome.
abstract: Betatrophin is a newly identified hormone determined to be a potent inducer of pancreatic beta cell proliferation in response to insulin resistance in mice. Polycystic ovary syndrome (PCOS) is an inflammatory-based metabolic disease associated with insulin resistance. However, no evidence is available indicating whether betatrophin is involved in women with PCOS. The objective of this study was to ascertain whether betatrophin levels are altered in women with PCOS. This study was conducted in secondary referral center. This cross-sectional study included 164 women with PCOS and 164 age- and BMI-matched female controls. Circulating betatrophin levels were measured using ELISA. Metabolic and hormonal parameters were also determined. Circulating betatrophin levels were significantly elevated in women with PCOS compared with controls (367.09 ± 55.78 vs. 295.65 ± 48.97 pg/ml, P < 0.001). Betatrophin levels were positively correlated with insulin resistance marker homeostasis model assessment of insulin resistance (HOMA-IR), free-testosterone, high-sensitivity C-reactive protein (hs-CRP), atherogenic lipid profiles, and BMI in PCOS. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.51 for patients in the highest quartile of betatrophin compared with those in the lowest quartile (95 % CI 1.31-4.81, P = 0.006). Multivariate regression analyses showed that HOMA-IR, hs-CRP, and free-testosterone were independent factors influencing serum betatrophin levels. Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, hs-CRP, and free-testosterone in these patients. Elevated betatrophin levels were found to increase the odds of having PCOS. Further research is needed to elucidate the physiologic and pathologic significance of our findings.
authors.affiliation: Division of Endocrinology and Metabolism (PCOS Research Group), Department of Internal Medicine, Dokuz Eylul University Medical School, Inciralti, 35340, Izmir, Turkey. drmehmetcalan@gmail.com.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Calan
authors.affiliation: Department of Obstetrics and Gynecology (PCOS Research Group), Manisa Merkezefendi State Hospital, Merkezefendi, 45020, Manisa, Turkey.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Yilmaz
authors.affiliation: Department of Biochemistry and Clinical Biochemistry, Dokuz Eylul University Faculty of Medicine, Inciralti, 35340, Izmir, Turkey.
authors.forename: Tuncay
authors.initials: T
authors.lastname: Kume
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine (PCOS Research Group), Izmir Bozyaka Training and Research Hospital, Bozyaka, 35170, Izmir, Turkey.
authors.forename: Gokcen
authors.initials: G
authors.lastname: Unal Kocabas
authors.affiliation: Department of Bioengineering, Ege University, Bornova, 35100, Izmir, Turkey.
authors.forename: Pinar
authors.initials: P
authors.lastname: Yesil Senses
authors.affiliation: Department of Biotechnology, Ege University, Bornova, 35100, Izmir, Turkey.
authors.forename: Yasar Mehmet
authors.initials: YM
authors.lastname: Senses
authors.affiliation: Department of Obstetrics and Gynecology (PCOS Research Group), Manisa Merkezefendi State Hospital, Merkezefendi, 45020, Manisa, Turkey.
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Temur
authors.affiliation: Department of Biochemistry and Clinical Biochemistry, Dokuz Eylul University Faculty of Medicine, Inciralti, 35340, Izmir, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Gursoy Calan
mesh_terms: D000328:Adult; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D036361:Peptide Hormones / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000175:diagnosis*; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D015415:Biomarkers; D008055:Lipids; D036361:Peptide Hormones; D013739:Testosterone; D002097:C-Reactive Protein
keywords: Betatrophin; Free-testosterone; Insulin resistance; Lipids; Polycystic ovary syndrome
references.citation: Diabetologia. 2014 Jun;57(6):1204-8
references.pmid: 24623100
references.citation: Am J Physiol Endocrinol Metab. 2012 Aug 1;303(3):E334-51
references.pmid: 22569073
references.citation: Diabet Med. 2014 Mar;31(3):273-81
references.pmid: 24341419
references.citation: Cell. 2013 May 9;153(4):747-58
references.pmid: 23623304
references.citation: Hum Reprod. 2004 Jan;19(1):41-7
references.pmid: 14688154
references.citation: Cell. 2014 Oct 23;159(3):691-6
references.pmid: 25417115
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19751-6
references.pmid: 23150577
references.citation: Int J Endocrinol. 2014;2014:323407
references.pmid: 24963292
references.citation: Steroids. 2013 Aug;78(8):773-6
references.pmid: 23624351
references.citation: Nat Clin Pract Endocrinol Metab. 2008 Apr;4(4):215-22
references.pmid: 18250636
references.citation: J Clin Endocrinol Metab. 2015 Jan;100(1):E96-100
references.pmid: 25303484
references.citation: J Clin Endocrinol Metab. 2014 Oct;99(10):E2004-9
references.pmid: 25050901
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16109-14
references.pmid: 24043787
references.citation: PLoS One. 2015 Jun 26;10(6):e0131171
references.pmid: 26115519
references.citation: Diabetes Care. 2008 Feb;31 Suppl 2:S262-8
references.pmid: 18227495
references.citation: PLoS One. 2015 Aug 06;10(8):e0133640
references.pmid: 26247824
references.citation: Clin Endocrinol (Oxf). 2013 Jun;78(6):926-34
references.pmid: 23046078
references.citation: J Clin Endocrinol Metab. 1961 Nov;21:1440-7
references.pmid: 13892577
references.citation: Gynecol Endocrinol. 2015;31(8):652-6
references.pmid: 26291796
references.citation: Am J Hum Genet. 2014 Feb 6;94(2):223-32
references.pmid: 24507774
references.citation: J Clin Endocrinol Metab. 2002 May;87(5):2013-7
references.pmid: 11994334
references.citation: Fertil Steril. 2002 Jun;77(6):1095-105
references.pmid: 12057712
references.citation: J Clin Endocrinol Metab. 2010 May;95(5):2038-49
references.pmid: 20375205
references.citation: Biochem Biophys Res Commun. 2012 Aug 10;424(4):786-92
references.pmid: 22809513
references.citation: Eur J Endocrinol. 2015 Jul;173(1):1-7
references.pmid: 25850828
references.citation: J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9
references.pmid: 15181052
references.citation: Nat Rev Endocrinol. 2011 Apr;7(4):219-31
references.pmid: 21263450
references.citation: Endocr Rev. 2012 Dec;33(6):981-1030
references.pmid: 23065822
references.citation: J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92
references.pmid: 24151290
references.citation: N Engl J Med. 2005 Mar 24;352(12):1223-36
references.pmid: 15788499
references.citation: Sci Rep. 2015 Jun 16;5:10949
references.pmid: 26077345
references.citation: J Med Genet. 2013 May;50(5):298-308
references.pmid: 23505323
references.citation: Endocr Rev. 1997 Dec;18(6):774-800
references.pmid: 9408743
references.citation: Diabetologia. 1985 Jul;28(7):412-9
references.pmid: 3899825
references.citation: Nat Rev Endocrinol. 2014 Oct;10(10):624-36
references.pmid: 25022814
references.citation: Diabetes Care. 2014 Oct;37(10):2718-22
references.pmid: 25024395