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Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome

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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.

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Abbreviations

ANGPLT8:

Angiopoetin-like 8 protein

BMI:

Body mass index

CI:

Confidence interval

CV:

Coefficient of variability

DHEA-S:

Dehydroepiandrosterone sulfate

E2 :

Estradiol

FBG:

Fasting blood glucose

FG:

Ferriman–Gallwey

GDM:

Gestational diabetes mellitus

HDL-C:

High-density lipoprotein cholesterol

HOMA-IR:

Homeostasis model assessment of insulin resistance

hs-CRP:

High-sensitivity C-reactive protein

LDL-C:

Low-density lipoprotein cholesterol

OR:

Odds ratio

PCOS:

Polycystic ovary syndrome

RIFL:

Re-feeding induced fat and liver protein

TD26:

Hepatocellular carcinoma-associated protein

T2DM:

Type 2 diabetes mellitus

VIF:

Variance inflation factor

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Acknowledgments

M.C., G.U.K., O.Y., and O.G.C. participated in study design and performed ELISA. M.C., P.Y., Y.M.S., and T.K. participated in study design, analyzed the data, wrote, reviewed, and edited the manuscript. O.Y. and M.T. provided serum samples and contributed to discussions of data interpretation. M.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism (PCOS Research Group), Department of Internal Medicine, Dokuz Eylul University Medical School, Inciralti, 35340, Izmir, Turkey

    Mehmet Calan

  2. Department of Obstetrics and Gynecology (PCOS Research Group), Manisa Merkezefendi State Hospital, Merkezefendi, 45020, Manisa, Turkey

    Ozgur Yilmaz & Muzaffer Temur

  3. Department of Biochemistry and Clinical Biochemistry, Dokuz Eylul University Faculty of Medicine, Inciralti, 35340, Izmir, Turkey

    Tuncay Kume & Ozlem Gursoy Calan

  4. Division of Endocrinology and Metabolism, Department of Internal Medicine (PCOS Research Group), Izmir Bozyaka Training and Research Hospital, Bozyaka, 35170, Izmir, Turkey

    Gokcen Unal Kocabas

  5. Department of Bioengineering, Ege University, Bornova, 35100, Izmir, Turkey

    Pinar Yesil Senses

  6. Department of Biotechnology, Ege University, Bornova, 35100, Izmir, Turkey

    Yasar Mehmet Senses

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  1. Mehmet Calan
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Calan, M., Yilmaz, O., Kume, T. et al. Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome. Endocrine 53, 271–279 (2016). https://doi.org/10.1007/s12020-016-0875-z

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  • DOI: https://doi.org/10.1007/s12020-016-0875-z

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