Download PDF
Exp Clin Endocrinol Diabetes 2021; 129(10): 705-712
DOI: 10.1055/a-1025-3711
Article

Several Circulating Biomarkers for PCOS Diagnosis

Peiqi Luo‡
1   Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
,
Cheng Zhang‡
1   Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
2   The Center of Clinical Research of Endocrinology and Metabolic Diseases in Chongqing and Department of Endocrinology, Chongqing Three Gorges Central Hospital, Chongqing, China
,
Yirui He‡
3   Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
,
Gangyi Yang
3   Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
,
Hua Liu
4   Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi, USA
,
Ling Li
1   Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, Chongqing, China
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Aims Irisin, Betatrophin and Zinc-α2-glycoprotein (ZAG) have been shown to be associated with insulin resistance (IR) and polycystic ovary syndrome (PCOS), respectively. The purpose of this study is to explore the potential accuracy of this combination of three cytokines in screening PCOS.

Methods 186 individuals were recruited for this study. Circulating Irisin, Betatrophin and ZAG concentrations were measured by enzyme-linked immunosorbent assay. The association between these serum biomarkers and PCOS was assessed by logistic regression analysis. Receiver operating curve (ROC) analysis was performed to evaluate the diagnostic value of these biomarkers for PCOS women.

Results In women with PCOS, serum Irisin and Betatrophin levels were markedly elevated compared to those in healthy controls (p<0.01), while ZAG levels were lower (p<0.01). PCOS women with IR (M-value<6.28) had lower circulating ZAG concentrations, and higher circulating Irisin and Betatrophin levels relative to PCOS women without IR (M-value ≥ 6.28). ROC curve analyses showed that the AUC for Irisin, ZAG and Betatrophin for predicting PCOS were 0.77, 0.83 and 0.85, respectively. In a joint ROC curves analysis of these serum markers and other parameters, the results showed that the AUC was 0.93, and the sensitivity and specificity were 82.1 % and 92.3 %, respectively.

Conclusions When compared to using single cytokine, the analysis of Irisin, ZAG and Betatrophin elevates the accuracy in diagnosing PCOS.

Key words

biomarker - cytokine - insulin resistance - PCOS


Publication History

Received: 15 July 2019
Received: 04 October 2019

Accepted: 10 October 2019

Article published online:
04 November 2019

© 2019. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Calan M, Yilmaz O, Kume T. et al. Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome. Endocrine 2016; 53: 271-279
    CrossrefPubMedGoogle Scholar
  • 2 Azziz R, Carmina E, Dewailly D. et al. Positions statement: Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: An androgen excess society guideline. J Clin Endocrinol Metab 2006; 91: 4237-4245
    CrossrefPubMedGoogle Scholar
  • 3 Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352: 1223-1236
    CrossrefPubMedGoogle Scholar
  • 4 Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab 2006; 91: 492-497
    CrossrefPubMedGoogle Scholar
  • 5 Lewy VD, Danadian K, Witchel SF. et al. Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J Pediatr 2001; 138: 38-44
    CrossrefPubMedGoogle Scholar
  • 6 Palmert MR, Gordon CM, Kartashov AI. et al. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 1017-1023
    CrossrefPubMedGoogle Scholar
  • 7 Tfayli H, Arslanian S. Menstrual health and the metabolic syndrome in adolescents. Ann NY Acad Sci 2008; 1135: 85-94
    CrossrefPubMedGoogle Scholar
  • 8 Arslanian SA, Lewy VD, Danadian K. Glucose intolerance in obese adolescents with polycystic ovary syndrome: Roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease. J Clin Endocrinol Metab 2001; 86: 66-71
    PubMedGoogle Scholar
  • 9 Tfayli H, Ulnach JW, Lee S. et al. Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: Comparison of metabolic, hormonal, and cardiovascular risk factors. J Clin Endocrinol Metab 2011; 96: 1311-1319
    CrossrefPubMedGoogle Scholar
  • 10 Yang M, Liu R, Li S. et al. Zinc-alpha2-glycoprotein is associated with insulin resistance in humans and is regulated by hyperglycemia, hyperinsulinemia, or liraglutide administration: Cross-sectional and interventional studies in normal subjects, insulin-resistant subjects, and subjects with newly diagnosed diabetes. Diabetes Care 2013; 36: 1074-1082
    CrossrefPubMedGoogle Scholar
  • 11 Li M, Yang M, Zhou X. et al. Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2015; 100: 1485-1493
    CrossrefPubMedGoogle Scholar
  • 12 Wang H, Du L, Wu T. et al. Circulating betatrophin is associated with insulin resistance in humans: cross-sectional and interventional studies in vivo and in vitro. Oncotarget 2017; 8: 96604-96614
    CrossrefPubMedGoogle Scholar
  • 13 Gomez-Ambrosi J, Pascual E, Catalan V. et al. Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes. J Clin Endocrinol Metab 2014; 99: E2004-E2009
    CrossrefPubMedGoogle Scholar
  • 14 Moreno-Navarrete JM, Ortega F, Serrano M. et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 2013; 98: E769-E778
    CrossrefPubMedGoogle Scholar
  • 15 Rolli V, Radosavljevic M, Astier V. et al. Lipolysis is altered in MHC class I zinc-alpha(2)-glycoprotein deficient mice. FEBS Lett 2007; 581: 394-400
    CrossrefPubMedGoogle Scholar
  • 16 [Anonymous]. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
    CrossrefPubMedGoogle Scholar
  • 17 Li K, Liao X, Wang K. et al. Myonectin predicts the development of type 2 diabetes. J Clin Endocrinol Metab 2018; 103: 139-147
    CrossrefPubMedGoogle Scholar
  • 18 Albareda M, Rodriguez-Espinosa J, Murugo M. et al. Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 2000; 43: 1507-1511
    CrossrefPubMedGoogle Scholar
  • 19 Fang X, Zhang T, Yang M. et al. High circulating alarin levels are associated with presence of metabolic syndrome. Cell Physiol Biochem 2018; 51: 2041-2051
    CrossrefPubMedGoogle Scholar
  • 20 Rana KS, Pararasa C, Afzal I. et al. Plasma irisin is elevated in type 2 diabetes and is associated with increased E-selectin levels. Cardiovasc Diabetol 2017; 16: 147
    CrossrefPubMedGoogle Scholar
  • 21 Shanaki M, Moradi N, Emamgholipour S. et al. Lower circulating irisin is associated with nonalcoholic fatty liver disease and type 2 diabetes. Diabetes Metab Syndr 2017; 11 (Suppl. 01) S467-s472
    CrossrefPubMedGoogle Scholar
  • 22 Akour A, Kasabri V, Boulatova N. et al. Levels of metabolic markers in drug-naive prediabetic and type 2 diabetic patients. Acta Diabetol 2017; 54: 163-170
    CrossrefPubMedGoogle Scholar
  • 23 Chang CL, Huang SY, Hsu YC. et al. The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients. Sci Rep 2019; 9: 6447
    CrossrefPubMedGoogle Scholar
  • 24 Cai X, Qiu S, Li L. et al. Circulating irisin in patients with polycystic ovary syndrome: A meta-analysis. Reprod Biomed Online 2018; 36: 172-180
    CrossrefPubMedGoogle Scholar
  • 25 Wang W, Guo Y, Zhang X. et al. Abnormal irisin level in serum and endometrium is associated with metabolic dysfunction in polycystic ovary syndrome patients. Clin Endocrinol (Oxf) 2018; 89: 474-480
    CrossrefPubMedGoogle Scholar
  • 26 Adamska A, Karczewska-Kupczewska M, Lebkowska A. et al. Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome. Endocr J 2016; 63: 1107-1112
    CrossrefPubMedGoogle Scholar
  • 27 Lai Y, Chen J, Li L. et al. Circulating Zinc-alpha2-glycoprotein levels and insulin resistance in polycystic ovary syndrome. Sci Rep 2016; 6: 25934
    CrossrefPubMedGoogle Scholar
  • 28 Zheng S, Liu E, Zhang Y. et al. Circulating zinc-alpha2-glycoprotein is reduced in women with polycystic ovary syndrome, but can be increased by exenatide or metformin treatment. Endocr J 2019; 66: 555-562
    CrossrefPubMedGoogle Scholar
  • 29 Varikasuvu SR, Panga JR, Satyanarayana MV. Circulating Angiopoietin-like 8 protein (ANGPTL8/Betatrophin) in patients with polycystic ovary syndrome: A systematic review and multi effect size meta-analysis. Gynecol Endocrinol 2019; 35: 190-197
    CrossrefPubMedGoogle Scholar
  • 30 Eksi Haydardedeoglu F, Bagir GS, Haydardedeoglu B. et al. Serum betatrophin levels are reduced in patients with full-blown polycystic ovary syndrome. Gynecol Endocrinol 2019; 35: 224-227
    CrossrefPubMedGoogle Scholar
  • 31 Kahraman S, Altinova AE, Yalcin MM. et al. Association of serum betatrophin with fibroblast growth factor-21 in women with polycystic ovary syndrome. J Endocrinol Invest 2018; 41: 1069-1074
    CrossrefPubMedGoogle Scholar
  • 32 Adamska A, Lebkowska A, Jacewicz M. et al. Serum concentrations of betatrophin and its association with indirect indices of insulin resistance and beta cell function in women with polycystic ovary syndrome. Int J Endocrinol 2017; 2316986
    PubMedGoogle Scholar
  • 33 Erol O, Ozel MK, Ellidag HY. et al. Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome. J Obstet Gynaecol 2017; 37: 633-638
    CrossrefPubMedGoogle Scholar
  • 34 Erbag G, Eroglu M, Turkon H. et al. Relationship between betatrophin levels and metabolic parameters in patients with polycystic ovary syndrome. Cell Mol Biol (Noisy-le-grand) 2016; 62: 20-24
    PubMedGoogle Scholar