Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome

Meryem Kuru Pekcan; Aytekin Tokmak; Hatice Akkaya; Gültekin Pekcan; Andaç Onur; Üçler Kısa; Aylin Pelin Çil

doi:10.1055/a-0867-0886

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2019; 51(04): 261-266
DOI: 10.1055/a-0867-0886

Endocrine Care

Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome

Authors

Meryem Kuru Pekcan

¹Department of Obstetrics and Gynecology, University of Health Sciences, Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey
Aytekin Tokmak

¹Department of Obstetrics and Gynecology, University of Health Sciences, Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey
Hatice Akkaya

¹Department of Obstetrics and Gynecology, University of Health Sciences, Zekai Tahir Burak Women's Health Research and Education Hospital, Ankara, Turkey
Gültekin Pekcan

²Department of Internal Medicine, Ankara University Medical Faculty, Ankara, Turkey
Andaç Onur

³Department of Medical Biochemistry, Numune Training and Research Hospital, Ankara, Turkey
Üçler Kısa

⁴Department of Medical Biochemistry, Kirikkale University Faculty of Medicine, Kirikkale, Turkey
Aylin Pelin Çil

⁵VKV American Hospital, Women's Healthcare Centre, Istanbul, Turkey

Abstract

The purpose of this study was to assess the rate of insulin resistance (IR) and the relationship between IR and high-molecular weight adiponectin (HMWA) in patients with polycystic ovary syndrome (PCOS). A cross sectional study involving 43 women with PCOS and 39 normal women was carried out over a period of nine months. Fasting glucose and insulin levels, lipid parameters and androgen levels were measured in all serum samples. HMWA was determined by enzyme-linked immunosorbent assay and IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The IR was more prevalent in the PCOS group than in the controls (p=0.002). Dehydroepiandrosterone sulfate, sex hormone binding globulin, free androgen index, total testosterone, insulin, and HOMA-IR levels were significantly higher in the PCOS group as compared to the control group (all p<0.05). Moreover, HMWA was significantly lower and negatively correlated with the clinical and biochemical hyperandrogenism in the PCOS group. HMWA and HOMA-IR were also associated with triglyceride, body mass index, and fat mass in this group. ROC curve analyses demonstrated that the AUC, indicative of the HMWA value for discriminating PCOS with IR, was 0.725, with a confidence interval of 0.615–0.835 (p=0.001). The serum HMWA levels are lower in patients with PCOS, which suggest that HMWA might be involved in the pathogenesis of PCOS. We also conclude that HMWA might be a strong determinant of IR in PCOS patients.

Key words

polycystic ovarian syndrome - high-molecular weight adiponectin - insulin resistance - hyperandrogenemia - HOMA-IR

Full Text

References

References
1 Diamanti-Kandarakis E, Kouli CR, Bergiele AT. et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999; 84: 4006-4011
2 Azziz R, Carmina E, Dewailly D. et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456-488
3 Elting MW, Korsen TJ, Bezemer PD. et al. Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Hum Reprod 2001; 16: 556-560
4 Liu X, Zhang J, Li Y. et al. On the relationship between serum total adiponectin and insulin resistance in polycystic ovary syndrome. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2010; 27: 636-640
5 Vrbíková J, Dvoráková K, Hill M. et al. Determinants of circulating adiponectin in women with polycystic ovary syndrome. Gynecol Obstet Invest 2005; 60: 155-161
6 Yamauchi T, Kamon J, Waki H. et al. The fat derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946
7 Weyer C, Funahashi T, Tanaka S. et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930-1935
8 Aroda V, Ciaraldi TP, Chang SA. et al. Circulating and cellular adiponectin in polycystic ovary syndrome: Relationship to glucose tolerance and insulin action. Fertil Steril 2008; 89: 1200-1208
9 Tsao TS, Tomas E, Murrey HE. et al. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem 2003; 278: 50810-50817
10 Pajvani UB, Du X, Combs TP. et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J Biol Chem 2003; 278: 9073-9085
11 Fisher FM, Trujillo ME, Hanif W. et al. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia 2005; 48: 1084-1087
12 Hara K, Horikoshi M, Yamauchi T. et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 2006; 29: 1357-1362
13 Lara-Castro C, Luo N, Wallace P. et al. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 2006; 55: 249-259
14 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovarian syndrome. Fertil Steril 2004; 8: 19-25
15 American Diabetes Association . Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37: S81-S90
16 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
17 Li S, Huang X, Zhong H. et al. Low circulating adiponectin levels in women with polycystic ovary syndrome: An updated meta-analysis. Tumour Biol 2014; 35: 3961-3973
18 Toulis KA, Goulis DG, Farmakiotis D. et al. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update 2009; 15: 297-307
19 Glintborg D, Frystyk J, Højlund K. et al. Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome. Clin Endocrinol (Oxf) 2008; 68: 165-174
20 Blouin K, Boivin A, Tchernof A. Androgens and body fat distribution. J Steroid Biochem Mol Biol 2008; 108: 272-280
21 Bays HE, González-Campoy JM, Bray GA. et al. Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Rev Cardiovasc Ther 2008; 6: 343-368
22 Gavrila A, Chan JL, Yiannakouris N. et al. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: Cross-sectional and interventional studies. J Clin Endocrinol Metab 2003; 88: 4823-4831
23 Ardawi MS, Rouzi AA. Plasma adiponectin and insulin resistance in women with polycystic ovary syndrome. Fertil Steril 2005; 83: 1708-1716
24 DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: 214-223
25 Mather KJ, Hunt AE, Steinberg HO. et al. Repeatability characteristics of simple indices of insulin resistance: Implications for research applications. J Clin Endocrinol Metab 2001; 86: 5457-5464
26 Cankaya S, Demir B, Aksakal SE. et al. Insulin resistance and its relationship with high molecular weight adiponectin in adolescents with polycystic ovary syndrome and a maternal history of polycystic ovary syndrome. Fertil Steril 2014; 102: 826-830
27 Tao T, Xu B, Liu W. Ovarian HMW adiponectin is associated with folliculogenesis in women with polycystic ovary syndrome. Reprod Biol Endocrinol 2013; 11: 99
28 Gorgani-Firuzjaee S, Khatami S, Meshkani R. SH2 domain-containing inositol 5-phosphatase (SHIP2) regulates de-novo lipogenesis and secretion of apoB100 containing lipoproteins in HepG2 cells. Biochem Biophys Res Commun 2015; 464: 1028-1033
29 Rezvan N, Moini A, Janani L. et al. Effects of Quercetin on Adiponectin-Mediated Insulin Sensitivity in Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Double-Blind Clinical Trial. Horm Metab Res 2017; 49: 115-121
30 Xita N, Georgiou I, Chatzikyriakidou A. et al. Effect of adiponectin gene polymorphisms on circulating adiponectin and insulin resistance indexes in women with polycystic ovary syndrome. Clin Chem 2005; 51: 416-423
31 Moran LJ, Teede HJ, Noakes M. et al. Sex hormone binding globulin, but not testosterone, is associated with the metabolic syndrome in overweight and obese women with polycystic ovary syndrome. J Endocrinol Invest 2013; 36: 1004-1010
32 Cassar S, Teede HJ, Harrison CL. et al. Biomarkers and insulin sensitivity in women with PCOS: characteristics and predictive capacity. Clin Endocrinol (Oxf) 2015; 83: 50-58
33 Cassar S, Misso ML, Hopkins WG. et al. Insulin resistance in polycystic ovary syndrome: A systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Hum Reprod 2016; 31: 2619-2631