Pericardial Fat Relates to Disturbances of Glucose Metabolism in Women with the Polycystic Ovary Syndrome, but Not in Healthy Control Subjects

Michael Leutner, Christian Göbl, Peter Wolf, Katharina Maruszczak, Latife Bozkurt, Helmut Steinbrecher, Ivica Just-Kukurova, Johannes Ott, Christian Egarter, Siegfried Trattnig, Alexandra Kautzky-Willer, Michael Leutner, Christian Göbl, Peter Wolf, Katharina Maruszczak, Latife Bozkurt, Helmut Steinbrecher, Ivica Just-Kukurova, Johannes Ott, Christian Egarter, Siegfried Trattnig, Alexandra Kautzky-Willer

Abstract

Objective: The objective of the present study is to investigate the relationship of cardiac fat depots with disturbances of the carbohydrate metabolism in women with PCOS.

Methods: An oral glucose tolerance test (OGTT) was realized, and metabolic parameters were collected in 48 women with PCOS and in 20 controls. Intramyocardial fat (MYCL) and pericardial fat (PERI) were measured using 1H-magnetic resonance spectroscopy and imaging.

Results: Only in PCOS women, PERI was positively and independently related to parameters of glucose metabolism (HbA1c: p = 0.001, fasting plasma glucose: p < 0.001, stimulated glucose at 30 and 60 minutes in the OGTT). Thus, the disposition index, insulin sensitivity, and adiponectin also declined with the increase of PERI in women with PCOS; however, these results were not independent of BMI and age. In addition, PERI was positively related to atherogenic lipid profiles, BMI, waist circumference, CRP, and liver fat in women with PCOS. A negative relation of PERI with triglycerides and a positive relation with BMI and waist circumference could be observed in the controls. No relationship of MYCL with diabetes-specific parameters could be found in the study population.

Conclusion: PERI is related to metabolic disturbances in women with PCOS, but not in metabolically healthy lean subjects. This clinical trial was registered at ClinicalTrials.gov and has the registration number NCT03204461.

Figures

Figure 1
Figure 1
Correlation analyses of PERI with fasting plasma glucose in PCOS women and control subjects.

References

    1. March W. A., Moore V. M., Willson K. J., Phillips D. I. W., Norman R. J., Davies M. J. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human Reproduction. 2010;25(2):544–551. doi: 10.1093/humrep/dep399.
    1. Nestler J. E. Metformin for the treatment of the polycystic ovary syndrome. The New England Journal of Medicine. 2008;358(1):47–54. doi: 10.1056/NEJMct0707092.
    1. Diamanti-Kandarakis E., Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocrine Reviews. 2012;33(6):981–1030. doi: 10.1210/er.2011-1034.
    1. Creanga A. A., Bradley H. M., McCormick C., Witkop C. T. Use of metformin in polycystic ovary syndrome: a meta-analysis. Obstetrics and Gynecology. 2008;111(4):959–968. doi: 10.1097/AOG.0b013e31816a4ed4.
    1. Brzozowska M. M., Ostapowicz G., Weltman M. D. An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome. Journal of Gastroenterology and Hepatology. 2009;24(2):243–247. doi: 10.1111/j.1440-1746.2008.05740.x.
    1. Cerda C., Pérez-Ayuso R. M., Riquelme A., et al. Nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Journal of Hepatology. 2007;47(3):412–417. doi: 10.1016/j.jhep.2007.04.012.
    1. Göbl C. S., Ott J., Bozkurt L., et al. To assess the association between glucose metabolism and ectopic lipid content in different clinical classifications of PCOS. PLoS One. 2016;11(8, article e0160571) doi: 10.1371/journal.pone.0160571.
    1. Iacobellis G., Leonetti F. Epicardial adipose tissue and insulin resistance in obese subjects. The Journal of Clinical Endocrinology and Metabolism. 2005;90(11):6300–6302. doi: 10.1210/jc.2005-1087.
    1. McGavock J. M., Lingvay I., Zib I., et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation. 2007;116(10):1170–1175. doi: 10.1161/CIRCULATIONAHA.106.645614.
    1. Iozzo P., Lautamaki R., Borra R., et al. Contribution of glucose tolerance and gender to cardiac adiposity. The Journal of Clinical Endocrinology and Metabolism. 2009;94(11):4472–4482. doi: 10.1210/jc.2009-0436.
    1. Arpaci D., Gurkan Tocoglu A., Yilmaz S., et al. The relationship between epicardial fat tissue thickness and visceral adipose tissue in lean patients with polycystic ovary syndrome. Journal of Ovarian Research. 2015;8(1):p. 71. doi: 10.1186/s13048-015-0197-4.
    1. Borruel S., Fernández-Durán E., Alpañés M., et al. Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS) The Journal of Clinical Endocrinology and Metabolism. 2013;98(3):1254–1263. doi: 10.1210/jc.2012-3698.
    1. Cakir E., Doğan M., Topaloglu O., et al. Subclinical atherosclerosis and hyperandrogenemia are independent risk factors for increased epicardial fat thickness in patients with PCOS and idiopathic hirsutism. Atherosclerosis. 2013;226(1):291–295. doi: 10.1016/j.atherosclerosis.2012.11.004.
    1. Sahin S. B., Cure M. C., Ugurlu Y., et al. Epicardial adipose tissue thickness and NGAL levels in women with polycystic ovary syndrome. Journal of Ovarian Research. 2014;7(1):p. 24. doi: 10.1186/1757-2215-7-24.
    1. Aydogdu A., Uckaya G., Tasci I., et al. The relationship of epicardial adipose tissue thickness to clinical and biochemical features in women with polycystic ovary syndrome. Endocrine Journal. 2012;59(6):509–516. doi: 10.1507/endocrj.EJ11-0328.
    1. Iacobellis G., Pistilli D., Gucciardo M., et al. Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine. 2005;29(6):251–255. doi: 10.1016/j.cyto.2004.11.002.
    1. Iacobellis G., Barbaro G., Gerstein H. C. Relationship of epicardial fat thickness and fasting glucose. International Journal of Cardiology. 2008;128(3):424–426. doi: 10.1016/j.ijcard.2007.12.072.
    1. Gaborit B., Kober F., Jacquier A., et al. Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat. International Journal of Obesity. 2012;36(3):422–430. doi: 10.1038/ijo.2011.117.
    1. Wolf P., Winhofer Y., Smajis S., et al. Pericardial-rather than intramyocardial fat is independently associated with left ventricular systolic heart function in metabolically healthy humans. PLoS One. 2016;11(3, article e0151301) doi: 10.1371/journal.pone.0151301.
    1. Krššák M., Winhofer Y., Göbl C., et al. Insulin resistance is not associated with myocardial steatosis in women. Diabetologia. 2011;54(7):1871–1878. doi: 10.1007/s00125-011-2146-0.
    1. Winhofer Y., Wolf P., Krššák M., et al. No evidence of ectopic lipid accumulation in the pathophysiology of the acromegalic cardiomyopathy. The Journal of Clinical Endocrinology and Metabolism. 2014;99(11):4299–4306. doi: 10.1210/jc.2014-2242.
    1. Scherer T., Wolf P., Winhofer Y., et al. Levothyroxine replacement in hypothyroid humans reduces myocardial lipid load and improves cardiac function. The Journal of Clinical Endocrinology and Metabolism. 2014;99(11):E2341–E2346. doi: 10.1210/jc.2014-2112.
    1. Matsuda M., DeFronzo R. A. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22(9):1462–1470. doi: 10.2337/diacare.22.9.1462.
    1. Mari A., Pacini G., Murphy E., Ludvik B., Nolan J. J. A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care. 2001;24(3):539–548. doi: 10.2337/diacare.24.3.539.
    1. Matthews D. R., Hosker J. P., Rudenski A. S., Naylor B. A., Treacher D. F., Turner R. C. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–419. doi: 10.1007/BF00280883.
    1. Tura A., Kautzky-Willer A., Pacini G. Insulinogenic indices from insulin and C-peptide: comparison of beta-cell function from OGTT and IVGTT. Diabetes Research and Clinical Practice. 2006;72(3):298–301. doi: 10.1016/j.diabres.2005.10.005.
    1. Jones H., Sprung V. S., Pugh C. J. A., et al. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. The Journal of Clinical Endocrinology and Metabolism. 2012;97(10):3709–3716. doi: 10.1210/jc.2012-1382.
    1. Fitzgibbons T. P., Czech M. P. Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations. Journal of the American Heart Association. 2014;3(2, article e000582) doi: 10.1161/JAHA.113.000582.
    1. Iacobellis G., Malavazos A. E., Corsi M. M. Epicardial fat: from the biomolecular aspects to the clinical practice. The International Journal of Biochemistry & Cell Biology. 2011;43(12):1651–1654. doi: 10.1016/j.biocel.2011.09.006.
    1. Wang T. D., Lee W. J., Shih F. Y., et al. Relations of epicardial adipose tissue measured by multidetector computed tomography to components of the metabolic syndrome are region-specific and independent of anthropometric indexes and intraabdominal visceral fat. The Journal of Clinical Endocrinology and Metabolism. 2009;94(2):662–669. doi: 10.1210/jc.2008-0834.
    1. Iacobellis G., Ribaudo M. C., Assael F., et al. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. The Journal of Clinical Endocrinology and Metabolism. 2003;88(11):5163–5168. doi: 10.1210/jc.2003-030698.
    1. Chen C.-I., Hsu M.-I., Lin S.-H., Chang Y.-C. I., Hsu C.-S., Tzeng C.-R. Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome. Gynecological Endocrinology. 2014;31(4):264–268. doi: 10.3109/09513590.2014.984676.
    1. Ling C., Svensson L., Odén B., et al. Identification of functional prolactin (PRL) receptor gene expression: PRL inhibits lipoprotein lipase activity in human white adipose tissue. The Journal of Clinical Endocrinology & Metabolism. 2003;88(4):1804–1808. doi: 10.1210/jc.2002-021137.
    1. Freemark M., Avril I., Fleenor D., et al. Targeted deletion of the PRL receptor: effects on islet development, insulin production, and glucose tolerance. Endocrinology. 2002;143(4):1378–1385. doi: 10.1210/endo.143.4.8722.
    1. Park S., Kim D. S., Daily J. W., Kim S. H. Serum prolactin concentrations determine whether they improve or impair β-cell function and insulin sensitivity in diabetic rats. Diabetes/Metabolism Research and Reviews. 2011;27(6):564–574. doi: 10.1002/dmrr.1215.
    1. Muniyappa R., Noureldin R., Ouwerkerk R., et al. Myocardial fat accumulation is independent of measures of insulin sensitivity. The Journal of Clinical Endocrinology and Metabolism. 2015;100(8):3060–3068. doi: 10.1210/jc.2015-1139.
    1. Victor V. M., Rocha M., Bañuls C., et al. Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance. The Journal of Clinical Endocrinology & Metabolism. 2011;96(10):3115–3122. doi: 10.1210/jc.2011-0651.
    1. Marchington J. M., Mattacks C. A., Pond C. M. Adipose tissue in the mammalian heart and pericardium: structure, foetal development and biochemical properties. Comparative Biochemistry and Physiology Part B: Comparative Biochemistry. 1989;94(2):225–232. doi: 10.1016/0305-0491(89)90337-4.
    1. Granér M., Siren R., Nyman K., et al. Cardiac steatosis associates with visceral obesity in nondiabetic obese men. The Journal of Clinical Endocrinology & Metabolism. 2013;98(3):1189–1197. doi: 10.1210/jc.2012-3190.

Source: PubMed

3
구독하다