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
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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.
Hu E, Liang P, Spiegelman BM . AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996; 271: 10697–10703.
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.
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.
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.
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.
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.
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.
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.
Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K . Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 2003; 14: 561–566.
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.
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.
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.
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.
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.
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.
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.
Chatterjee S, Hadi AS, Price B . Regression analysis by example. Wiley & Sons: New York, 2000.
Hanley AJG, Connelly PW, Harris SB, Zinman B . Adiponectin in a Native Canadian population experiencing rapid epidemiological transition. Diabet Care 2003; 26: 3219–3225.
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.
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.
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.
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.
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.
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.
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.
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.
Kanellis J, Kang DH . Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease. Semin Nephrol 2005; 25: 39–42.
Khosla UM, Zharikov S, Finch JL, Nakagawa T, Roncal C, Mu W et al. Hyperuricemia induces endothelial dysfunction. Kidney Int 2005; 67: 1739–1742.
Hattori S, Hattori Y, Kasai K . Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats. Metabolism 2005; 54: 482–487.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Corresponding author
Rights 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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0803471
Keywords
This article is cited by
-
Prevalence of metabolic syndrome in a cohort of Chinese schoolchildren: comparison of two definitions and assessment of adipokines as components by factor analysis
BMC Public Health (2013)
-
Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women
Acta Diabetologica (2012)
-
Inflammation: The Link Between Obesity and Cardiovascular Risk
Current Cardiovascular Risk Reports (2010)