Abstract
AIMS: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome.
SUBJECTS: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m2 (geometric mean 33.1±5.8kg/m2) and aged 19–71 y (mean 45.6±12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy.
RESULTS: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant (P<0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P<0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 (P<0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P<0.0001).
CONCLUSIONS: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.
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
Reaven GM . Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–1607.
Frayn KN . Adipose tissue and the insulin resistance syndrome. Proc Nutr Soc 2001; 60: 375–380.
Landsberg L . Role of the sympathetic adrenal system in the pathogenesis of the insulin resistance syndrome. Ann NY Acad Sci 1999; 892: 84–90.
Andrews RC, Walker BR . Glucocorticoids and insulin resistance: old hormones, new targets. Clin Sci 1999; 96: 513–523.
Bjorntorp P, Rosmond R . The metabolic syndrome—a neuroendocrine disorder? Br J Nutr 2000; 83 (Suppl 1): S49–S57.
Pickup JC, Crook MA . Is Type II diabetes mellitus a disease of the innate immune system? Diabetologia 1998; 41: 1241–1248.
Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB . Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group (see comments). Lancet 1997; 349: 462–466.
Ridker PM, Hennekens CH, Burling JE, Rifai N . C-Reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Eng J Med 2000; 342: 836–843.
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM . C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: 327–334.
Festa A, D'Agostino Jr R, Tracy RP, Haffner SM . Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 2002; 51: 1131–1137.
Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GD, O'Reilly DS, Packard CJ, Sattar N . C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 2002; 51: 1596–1600.
Festa A, D'Agostino Jr R, Howard G, Mykkanen L, Tracy RP, Haffner SM . Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2000; 102: 42–47.
Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB . Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282: 2131–2135.
Festa A, D'Agostino Jr R, Williams K, Karter AJ, Mayer-Davis EJ, Tracy RP, Haffner SM . The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord 2001; 25: 1407–1415.
Browning L, Krebs JD, Jebb SA . Discrimination ratio analysis of inflammatory markers: implications for the study of inflammation in chronic disease. Metabolism 2004, in press.
Lindberg G, Rastam L, Gullberg B, Lundblad A, Nilsson-Ehle P, Hanson BS . Serum concentrations of total sialic acid and sialoglycoproteins in relation to coronary heart disease risk markers. Atherosclerosis 1993; 103: 123–129.
Lindberg G, Rastam L, Gullberg B, Eklund GA . Serum sialic acid concentration predicts both coronary heart disease and stroke mortality: multivariate analysis including 54,385 men and women during 20.5 years follow-up. Int J Epidemiol 1992; 21: 253–257.
Schmidt MI, Duncan BB, Sharrett AR, Lindberg G, Savage PJ, Offenbacher S, Azambuja MI, Tracy RP, Heiss G . Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study. Lancet 1999; 353: 1649–1652.
Crook MA, Tutt P, Pickup JC . Elevated serum sialic acid concentration in NIDDM and its relationship to blood pressure and retinopathy. Diabetes Care 1993; 16: 57–60.
Friedewald WT, Levy RI, Frederickson DS . Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499–502.
WHO. Report of a WHO Consultation, Part 1: Diagnosis and Classification of Diabetes Mellitus, WHO/NCD/NCS/99.2. World Health Organisation: Geneva; 1999.
Danesh J . Smoldering arteries? Low-grade inflammation and coronary heart disease. JAMA 1999; 282: 2169–2171.
Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW . C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction. A potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19: 972–978.
Schauer R . Sialic Acids and their role as biological masks. TIBS 1985; 10: 357–360.
Pasceri V, Willerson JT, Yeh ET . Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165–2168.
Verma S, Li SH, Badiwala MV, Weisel RD, Fedak PW, Li RK, Dhillon B, Mickle DA . Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 2002; 105: 1890–1896.
Millar JS . The sialylation of plasma lipoproteins. Atherosclerosis 2001; 154: 1–13.
Orekhov AN, Tertov VV, Mukhin DN, Mikhailenko IA . Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients. Biochem Biophys Res Commun 1989; 162: 206–211.
Demuth K, Myara I, Chappey B, Vedie B, Pech-Amsellem MA, Haberland ME, Moatti N . A cytotoxic electronegative LDL subfraction is present in human plasma. Arterioscler Thromb Vasc Biol 1996; 16: 773–783.
Mann CJ, Troussard AA, Yen FT, Hannouche N, Najib J, Fruchart JC, Lotteau V, Andre P, Bihain BE . Inhibitory effects of specific apolipoprotein C-III isoforms on the binding of triglyceride-rich lipoproteins to the lipolysis-stimulated receptor. J Biol Chem 1997; 272: 31348–31354.
Zwaka TP, Homback V, Torzewski J . C-reactive protein-medicated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001; 103: 1194–1197.
Peraldi P, Spiegelman B . TNF-alpha and insulin resistance: summary and future prospects. Mol Cell Biochem 1998; 182: 169–175.
Baumann H, Gauldie J . The acute phase response. Immunol Today 1994; 15: 74–80.
Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA . The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol 2001; 280: E827–E847.
Lindsay RS, Bennett PH . Type 2 diabetes, the thrifty phenotype - an overview. Br Med Bull 2001; 60: 21–32.
Fernandez-Real JM, Ricart W . Insulin resistance and inflammation in an evolutionary perspective: the contribution of cytokine genotype/phenotype to thriftiness. Diabetologia 1999; 42: 1367–1374.
Acknowledgements
We thank Arlene McGowan, Shailja Nigdikar, Joanne Rothwell and Ian Halsall, who contributed to data collection and sample analysis and Dr Kirsten Rennie for comments on the manuscript. This study was funded by the Medical Research Council.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Browning, L., Jebb, S., Mishra, G. et al. Elevated sialic acid, but not CRP, predicts features of the metabolic syndrome independently of BMI in women. Int J Obes 28, 1004–1010 (2004). https://doi.org/10.1038/sj.ijo.0802711
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0802711
Keywords
This article is cited by
-
An integrated multi-omic approach demonstrates distinct molecular signatures between human obesity with and without metabolic complications: a case–control study
Journal of Translational Medicine (2023)
-
Sialic acids Neu5Ac and KDN in adipose tissue samples from individuals following habitual vegetarian or non-vegetarian dietary patterns
Scientific Reports (2023)
-
Non-alcoholic Fatty Liver Disease in Non-obese Patients
Current Hepatology Reports (2017)
-
Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study
BMC Medical Genomics (2010)
-
ω-3 oil intake during weight loss in obese women results in remodelling of plasma triglyceride and fatty acids
Metabolomics (2009)