Kahraman S, Altinova A E, Yalcin M M, Gulbahar O, Arslan B, Akturk M, Cakir N, Toruner F B

Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey.| Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Besevler, 06500, Ankara, Turkey. alevaltinova@yahoo.com.| Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Besevler, 06500, Ankara, Turkey.| Department of Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey.| Department of Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey.| Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Besevler, 06500, Ankara, Turkey.| Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Besevler, 06500, Ankara, Turkey.| Department of Endocrinology and Metabolism, Faculty of Medicine, Gazi University, Besevler, 06500, Ankara, Turkey.

J Endocrinol Invest. 2018 Sep;41(9):1069-1074. doi: 10.1007/s40618-018-0831-2.

PURPOSE: Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently discovered members of hepatokine/adipokine family, have been proposed to be associated with some metabolic disorders in which insulin resistance plays a major role.
METHODS: We aimed to investigate serum betatrophin and FGF-21 concentrations in women with polycystic ovary syndrome (PCOS). In this cross-sectional study, we recruited 31 women with PCOS and 34 women as healthy controls. Serum betatrophin level and its relationship with serum FGF-21 level as well as metabolic parameters were examined.
RESULTS: Serum betatrophin level was significantly higher in women with PCOS than the control group [1.10 (0.20-4.20) vs 0.70 (0.20-3.50) ng/ml, p = 0.004], whereas FGF-21 did not differ between the groups [74.80 (7.80-435.90) vs 119.30 (10.50-443.40) pg/ml, p = 0.13]. Serum betatrophin correlated positively with LH levels (r = 0.26, p = 0.03). After controlling BMI, there was a significant positive correlation between betatrophin and FGF-21 (r = 0.25, p = 0.04). Multivariate regression analysis revealed that FGF-21 and presence of PCOS were the significant predictors of betatrophin concentrations (R(2) = 0.22, F = 2.56, p = 0.03).
CONCLUSIONS: Our results indicate that betatrophin levels are increased and associated with LH and FGF-21 levels, but not with insulin resistance, in women with PCOS.

Erol Onur, Ozel Mustafa Kemal, Ellidag Hamit Yasar, Toptas Tayfun, Derbent Aysel Uysal, Yilmaz Necat

a Department of Obstetrics and Gynecology , Antalya Training and Research Hospital , Antalya , Turkey.| a Department of Obstetrics and Gynecology , Antalya Training and Research Hospital , Antalya , Turkey.| b Department of Biochemistry , Antalya Training and Research Hospital , Antalya , Turkey.| a Department of Obstetrics and Gynecology , Antalya Training and Research Hospital , Antalya , Turkey.| a Department of Obstetrics and Gynecology , Antalya Training and Research Hospital , Antalya , Turkey.| b Department of Biochemistry , Antalya Training and Research Hospital , Antalya , Turkey.

J Obstet Gynaecol. 2017 Jul;37(5):633-638. doi: 10.1080/01443615.2017.1286464.

The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m(2)) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

Qu Qinglan, Zhao Dongmei, Zhang Fengrong, Bao Hongchu, Yang Qiuhua

1 Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong, China.| 1 Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong, China.| 1 Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong, China.| 1 Department of Reproductive Medicine, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong, China.| 2 Department of Obstetrics, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong, China.

J Int Med Res. 2017 Feb;45(1):193-202. doi: 10.1177/0300060516680441. Epub 2017

Objective Betatrophin is a newly identified circulating protein that is significantly associated with type 2 diabetes mellitus (T2DM), adiposity, and metabolic syndrome. The aim of this study was to investigate whether betatrophin levels and polycystic ovary syndrome (PCOS) were associated. Methods Circulating betatrophin levels were measured in 162 patients with PCOS and 156 matched control females using specific enzyme-linked immunosorbent assay kits. Correlations between betatrophin levels and PCOS incidence as well as multiple key endocrine PCOS parameters were analyzed using multiple statistical methods. Results Betatrophin levels were significantly increased in patients with PCOS (685.3 +/- 27.7 vs. 772.6 +/- 42.5 pg/ml). When sub-grouping all investigated subjects according to the presence of insulin resistance, women with PCOS and insulin resistance exhibited markedly higher betatrophin concentrations. Furthermore, betatrophin levels were significantly correlated with fasting insulin levels and homeostatic model assessment of insulin resistance only in females with PCOS ( r = 0.531 and r = 0.628, respectively). Conclusion We provide the first report that betatrophin is strongly associated with PCOS. This study suggests that betatrophin may potentially serve as an independent predictor for the development of PCOS in at-risk women, especially those with insulin resistance.