Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Differential association of adiponectin with cardiovascular risk markers in men and women? The KORA survey 2000

Abstract

Background:

In men, high adiponectin concentrations were related to a lower risk of myocardial infarction, whereas no association with cardiovascular events was found in women.

Objective:

To investigate sex differences in the associations of adiponectin with cardiovascular risk factors.

Design:

Cross-sectional population-based KORA Survey 2000 in Southern Germany using the same study methods for cardiovascular risk factors as the former WHO MONICA project.

Participants:

A total of 697 men and 657 women, aged 55–74 years. Glucose tolerance status was assessed by oral glucose tolerance tests.

Results:

Adiponectin (geometric mean, interquartile range; μg/ml) levels were significantly higher in women (11.1; 8.5–14.9) than in men (7.1; 5.2–9.6) (P<0.05). In univariate analyses, HDL-cholesterol and age were significantly positively correlated with adiponectin in both sexes. Negative correlations were observed with BMI, waist circumference, fasting and postchallenge glucose, insulin, HOMA-IR, HbA1c, triglycerides, uric acid and CRP (P<0.01). In sex-specific multivariate regression, age and HDL-cholesterol were independently positively, and fasting insulin and 2-h glucose were negatively related to adiponectin in both sexes. Uric acid was significantly inversely related to adiponectin in women only (sex interaction: P=0.02). Exploratory sex-specific factor analysis of adiponectin and the core components of the metabolic syndrome yielded four similar factors. Adiponectin loaded negatively on the ‘lipids’ factor in both sexes.

Conclusion:

The associations of adiponectin with cardiovascular risk factors showed a similar pattern in both sexes, except for uric acid. This small sex difference may not explain previous conflicting results on the association of adiponectin with cardiovascular events in men and women.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Rabin KR, Kamari Y, Avni I, Grossman E, Sharabi Y . Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther 2005; 3: 465–471.

    Article  CAS  Google Scholar 

  2. Hu E, Liang P, Spiegelman BM . AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996; 271: 10697–10703.

    Article  CAS  Google Scholar 

  3. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20: 1595–1599.

    Article  CAS  Google Scholar 

  4. Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 2003; 23: 85–89.

    Article  CAS  Google Scholar 

  5. Rothenbacher D, Brenner H, März W, Koenig W . Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers. Eur Heart J 2005; 26: 1640–1646.

    Article  CAS  Google Scholar 

  6. Ridker PM, Hennekens CH, Buring JE, Rifai N . C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–843.

    Article  CAS  Google Scholar 

  7. Reilly MP, Iqbal N, Schutta M, Wolfe ML, Scally M, Localio AR et al. Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 3872–3878.

    Article  CAS  Google Scholar 

  8. Rothenbacher D, Müller-Scholze S, Herder C, Koenig W, Kolb H . Differential expression of chemokines, risk of stable coronary heart disease, and correlation with established cardiovascular risk markers. Arterioscler Thromb Vasc Biol 2006; 26: 194–199.

    Article  CAS  Google Scholar 

  9. Dietze-Schroeder D, Sell H, Uhlig M, Koenen M, Eckel J . Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors. Diabetes 2005; 54: 2003–2011.

    Article  CAS  Google Scholar 

  10. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K . Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 2003; 14: 561–566.

    Article  CAS  Google Scholar 

  11. Lindsay R, Resnick H, Ruotolo G . Adiponectin, relationship to proteinuria nut not coronary heart disease: the Strong Heart Study (Abstract). Arterioscler Thromb Vasc Biol 2003; 25: e15–e16.

    Google Scholar 

  12. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB . Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291: 1730–1737.

    Article  CAS  Google Scholar 

  13. Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB . Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005; 54: 534–539.

    Article  CAS  Google Scholar 

  14. Lawlor DA, Smith GD, Ebrahim S, Thompson C, Sattar N . Plasma adiponectin levels are associated with insulin resistance but do not predict future risk of coronary heart disease in women. J Clin Endocrinol Metab 2005; 90: 5677–5683.

    Article  CAS  Google Scholar 

  15. Efstathiou SP, Tsioulos DI, Tsiakou AG, Gratsias YE, Pefanis AV, Mountokalakis TD . Plasma adiponectin levels and five-year survival after first-ever ischemic stroke. Stroke 2005; 36: 1915–1920.

    Article  CAS  Google Scholar 

  16. Söderberg S, Stegmayr B, Stenlund H, Sjöström LG, Agren A, Johansson L et al. Leptin, but not adiponectin, predicts stroke in males. J Int Med 2004; 256: 128–136.

    Article  Google Scholar 

  17. Rathmann W, Haastert B, Icks A, Loewel H, Meisinger C, Holle R et al. High prevalence of undiagnosed diabetes mellitus in Southern Germany: target populations for efficient screening. The KORA survey 2000. Diabetologia 2003; 46: 182–189.

    Article  CAS  Google Scholar 

  18. Chatterjee S, Hadi AS, Price B . Regression analysis by example. Wiley & Sons: New York, 2000.

    Google Scholar 

  19. Hanley AJG, Connelly PW, Harris SB, Zinman B . Adiponectin in a Native Canadian population experiencing rapid epidemiological transition. Diabet Care 2003; 26: 3219–3225.

    Article  Google Scholar 

  20. Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68: 975–981.

    Article  CAS  Google Scholar 

  21. Schneider JG, Eynatten M, Schiekofer S, Nawroth PP, Dugi KA . Low plasma adiponectin levels are associated with increased hepatic lipase activity in vivo. Diabet Care 2005; 28: 2181–2186.

    Article  CAS  Google Scholar 

  22. Böttner A, Kratzsch J, Müller G, Kapellen TM, Blüher S, Keller E et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004; 89: 4053–4061.

    Article  Google Scholar 

  23. Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 2002; 51: 2734–2741.

    Article  CAS  Google Scholar 

  24. Lanfranco F, Zitzmann M, Simoni M, Nieschlag E . Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy. Clin Endocrinol 2004; 60: 500–507.

    Article  CAS  Google Scholar 

  25. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003; 46: 459–469.

    Article  CAS  Google Scholar 

  26. Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol 2005; 153: 91–98.

    Article  CAS  Google Scholar 

  27. Rathmann W, Funkhouser E, Dyer AR, Roseman JM . Relations of hyperuricemia with the various components of the insulin resistance syndrome in young black and white adults: the CARDIA Study. Coronary Artery Risk Development in Young Adults. Ann Epidemiol 1998; 8: 250–261.

    Article  CAS  Google Scholar 

  28. Kanellis J, Kang DH . Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol 2005; 25: 39–42.

    Article  CAS  Google Scholar 

  29. Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W et al. Hyperuricemia induces endothelial dysfunction. Kidney Int 2005; 67: 1739–1742.

    Article  Google Scholar 

  30. Hattori S, Hattori Y, Kasai K . Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats. Metabolism 2005; 54: 482–487.

    Article  CAS  Google Scholar 

  31. Soares AF, Guichardant M, Cozzone D, Bernoud-Hubac N, Buozaidi-Tiali N, Lagarde M et al. Effects of oxidative stress on adiponectin secretion and lactate production in 3T3-L1 adipocytes. Free Radic Biol Med 2005; 38: 882–889.

    Article  CAS  Google Scholar 

  32. Hayden MR, Tyagi SC . Uric acid: a new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: the urate redox shuttle. Nutr Metab 2004; 1: 1–15.

    Article  Google Scholar 

  33. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100: 2473–2476.

    Article  CAS  Google Scholar 

  34. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 2000; 102: 1296–1301.

    Article  CAS  Google Scholar 

  35. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000; 96: 1723–1732.

    CAS  Google Scholar 

  36. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103: 1057–1063.

    Article  CAS  Google Scholar 

  37. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278: 40352–40363.

    Article  CAS  Google Scholar 

  38. Meigs JB . Invited commentary: insulin resistance syndrome? Syndrome X? Multiple Metabolic Syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 2000; 152: 908–911.

    Article  CAS  Google Scholar 

  39. Pladevall M, Singal B, Williams LK, Brotons C, Guyer H, Sadurni J et al. A single factor underlies the metabolic syndrome. A confirmatory factor analysis. Diabet Care 2006; 29: 113–122.

    Article  Google Scholar 

  40. Mohan V, Deepa R, Pradeepa R, Vimaleswaran KS, Mohan A, Velmurugan K et al. Association of low adiponectin levels with the metabolic syndrome – the Chennai Urban Rural Epidemiology Study (CURES-4). Metabolism 2005; 54: 476–481.

    Article  CAS  Google Scholar 

  41. Xu A, Chan KW, Hoo RLC, Wang Y, Tan KCB, Zhang J et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem 2005; 280: 18073–18080.

    Article  CAS  Google Scholar 

  42. Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert MO et al. Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes 2005; 54: 2712–2719.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The OGTT study was partly funded by the German Federal Ministry of Health, the Ministry of School, Science and Research of the State of North-Rhine-Westfalia, and the Anna Wunderlich-Ernst Jühling Foundation (WR, GG). The KORA Survey 2000 was financed by the GSF, which is funded by the German Federal Ministry of Education, Science, Research and Technology and the State of Bavaria. The authors are indebted to K Papke (head of KORA Study Center) and B Schwertner (survey organization) and their coworkers for organizing and conducting the data collection. We are grateful to the KORA Study Group (Head: Professor HE Wichmann) for initiating the KORA Survey 2000. We also thank all participants of the OGTT study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W Rathmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rathmann, W., Haastert, B., Herder, C. et al. Differential association of adiponectin with cardiovascular risk markers in men and women? The KORA survey 2000. Int J Obes 31, 770–776 (2007). https://doi.org/10.1038/sj.ijo.0803471

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803471

Keywords

This article is cited by

Search

Quick links