Subscribe Now Subscribe Today
Research Article

Correlation of Plasma C-reactive Protein Levels to Sialic Acid and Lipid Concentrations in the Normal Population

Rajes Qvist, Ikram Shah Ismail, Sekaran Muniandy, Kumutha Malar Vellasamy and Karuthan Chinna
Facebook Twitter Digg Reddit Linkedin StumbleUpon E-mail

Aim of this study was to investigate the relationship between sialic acid component and C-reactive protein and lipids in the plasma of 80 healthy subjects. Levels of sialic acid, C-Reactive Protein (CRP) and plasma lipids were measured in a normal population consisting of 80 subjects. The possible correlation between sialic acid and CRP was also studied. The total sialic acid concentration was 2.61±0.61 mM L-1, CRP (2.52±2.32 mmole L-1), total cholesterol (5.50±1.28 mM L-1), triglycerides (1.31±0.87 mM L-1), low density lipoprotein (3.51±1.11 mM L-1) and high density lipoprotein (1.40±0.37 mM L-1). There was a positive correlation between sialic acid and CRP (r = 0.283, p<0.05). However, there was no correlation between CRP and the plasma lipids.

Related Articles in ASCI
Similar Articles in this Journal
Search in Google Scholar
View Citation
Report Citation

  How to cite this article:

Rajes Qvist, Ikram Shah Ismail, Sekaran Muniandy, Kumutha Malar Vellasamy and Karuthan Chinna, 2007. Correlation of Plasma C-reactive Protein Levels to Sialic Acid and Lipid Concentrations in the Normal Population. Journal of Medical Sciences, 7: 1049-1053.

DOI: 10.3923/jms.2007.1049.1053



The cause of Type 2 diabetes mellitus (non-insulin dependent) which affects millions of people throughout the world is not known. One of the foremost challenges is not only to account for hyperglycaemia, but also for the other biochemical abnormalities, which together with glucose tolerance, has been defined as metabolic syndrome X (Wajchenberg et al., 1994; Reaven, 1988). Although it is well established that insulin resistance and impaired insulin secretion are central to the pathogenesis of type 2 diabetes, it has been unclear how these abnormalities are related to the other biochemical features common in type 2 diabetes including central obesity, hypertension, accelerated atherosclerosis and dyslipidemia. However, inflammation has been implicated as part of the insulin resistance syndrome (Festa et al., 2000; Frohlich et al., 2000) and plays an important role in the onset and development and evolution of atherosclerotic lesions (Maseri, 1997).

There is increasing evidence that an ongoing cytokine induced acute phase response sometimes known as low grade inflammation is closely involved in the pathogenesis of type 2 diabetes and associated complications such as dyslipidemia and atherosclerosis (Pickup, 2004). Elevated circulating inflammatory markers such as C-Reactive Protein (CRP) and interleukin-6 predict the development of type 2 diabetes (Schmidt et al., 1999).

It is also known that CRP induces adhesion molecule expression in human endothelial cells in the presence of serum. These findings support the hypothesis that CRP may play a direct role in promoting the inflammatory component of atherosclerosis (Koenig et al.,1999; Lagrand et al., 1999). Previous reports suggest a positive association between components of the Insulin Resistance Syndrome (IRS) and the acute phase proteins, including CRP (Pickup, 2004). Lindberg et al. (1991) have shown that an elevated total serum sialic acid concentration is a risk factor for cardiovascular mortality in the general population. Nayak and Roberts (2006) have shown that serum sialic acid may be used as an inflammatory marker and possible indicator of complications among the Caribbean Type 2 diabetics. Since CRP is part of the acute phase response and sialic acid is present at the end of the carbohydrate moiety of the acute phase proteins (Lindberg et al., 1991), the objective of this study was to investigate the relationship between the sialic acid component and C-reactive protein in the plasma of 80 healthy subjects.


Subjects: Eighty healthy subjects were chosen from Klang Valley, Kuala Lumpur, through the distribution of questionnaires. Subjects Included were those without a family history of diabetes, hypertension, coronary artery disease and a body mass index of less than or equal to 30 kg m-2 without other cardiovascular risk factors. Equal number of males and females were chosen.

Methods: Fasting blood was collected in bottles containing disodium Ethylene Diamine Tetraacetate (EDTA) and the plasma was separated immediately by centrifugation at 3000 rpm for 15 min at 4°C. Total Cholesterol (TCH), triglycerides and High Density Lipoprotein (HDL) levels were determined using the individual biochemical kits supplied with DimensionR clinical chemistry system (Dode Behring, France) and Low Density Lipoprotein Levels (LDL) were determined by the Friedewald equation (Friedewald et al., 1972). Sialic acid was determined by the modification of the periodate resorcinol method as described by Jourdian et al. (1971) and CRP determined using Active CRP ELISA kit (Diagnostic Systems Laboratories, Webster) according to the manufacturer’s instructions.

VCAM-1 was measured using hsVCAM-1 ELISA kit (Boehringer Mannheim GmbH, Germany).

Statistical analysis: Data were expressed as mean±standard deviation. Bivariate Correlation (Pearson correlation coefficient) was used to study the correlation. Two tailed p-value of less than 0.05 was considered significant.


All subjects in this study were of comparable age and did not differ significantly in their body mass index. The mean concentrations of CRP, total sialic acid, TCH, triglycerides, HDL and LDL in the samples were determined (Table 1).

Table 1: Mean±SD of CRP, total sialic acid and plasma lipid concentrations

Fig. 1: Scatter plot of CRP vs VCAM-1

Fig. 2: Scatter plot of CRP vs Sialic Acid

Fig. 3: Scatter plot of CRP vs TCH

Fig. 4: Scatter plot of CRP vs Triglycerides

Fig. 5: Scatter plot of CRP vs LDL

Figure 1-6 show scatter plots of CRP levels versus VCAM-1, versus sialic acid and lipid levels.

Figure 1 shows a scatter plot of the correlation between CRP and VCAM-1.

Fig. 6: Scatter plot of CRP vs HDL

Table 2: Pearson correlation between CRP and the parameters VCAM1, sialic acid and plasma lipid concentrations
*Significant at p<0.05

There was a significant positive correlation between sialic acid and CRP (r = 0.283, p<0.05) among the 80 healthy subjects recruited (Table 2). Figure 1 shows a weak correlation between CRP and VCAM-1 (r = 0.095). Figure 3-6 shows a lack of correlation between CRP and TCH, triglycerides, LDL and HDL respectively.


Type 2 diabetes mellitus and atherosclerotic cardiovascular disease share many antecedent factors that frequently coexist, which has given rise to the concept of common soil (Jarrett and Shiply, 1988; Schmidt et al., 1996; Stern, 1995). This cluster of risk factors, such as uric acid and dyslipidaemia, are strongly related to fasting insulin concentrations and central obesity (Schmidt, 1996) and are also associated with raised concentration of inflammatory markers in people with and without diabetes (Yudkin, 1997; Pickup et al., 1997).

Inflammatory processes play a part in the cause of atherosclerotic cardiovascular disease (Ross, 1999). Concentrations of acute-phase response markers and mediators of inflammation such as tumor necrosis factor-alpha-1 (TNFα1) and interleukin-6 are raised in people with type 2 diabetes (Pickup et al., 1997; Nilsson et al., 1998). It has also been shown that some of the inflammatory markers such as CRP and sialic acid are increased in type 2 diabetes.

CRP, the classic acute-phase reactant, is an extremely sensitive systemic marker of inflammation (Chambers et al., 2001). It is a part of the immune response to injury and infection and it was shown to be an independent predictor of risk for the development of diabetes (Freeman, 2002). Sialic acid, a family of acetylated derivatives of neuraminic acid, is widely distributed in mammals. It usually occurs as a terminal component at the non-reducing end of carbohydrate chain of glycoproteins and glycolipids (Ng and Dain, 1976).

In present study, there was a good correlation between the C-reactive protein and sialic acid. Although we believe the link between cytokines and the acute phase response to be the most likely explanation for the association, some association may reflect other pathways linking acute phase reactants to alteration in insulin sensitivity or secretion. For instance removal of cell membrane sialic acid (perhaps through processes that shed sialic acid into the circulation, thereby raising its concentration) has been shown experimentally to induce insulin resistance (Salhanick and Amatruda, 1988).

Most of the acute phase proteins are glycoprotein with notable amount of sialic acid. In a Swedish population, orosomucoid, haptoglobin and α1-antitrypsin concentrations together explained 70% of the variability of total serum sialic acid concentration (Lindberg et al., 1993). Some studies have shown that the sialic acid concentrations are elevated in diabetics of both type 1 and type 2 with and without complications (Nayak and Roberts, 2006) while others have reported no such correlation (Abdella et al., 2000; Crook et al., 2002). Studies have also found that the presence or absence of this trend may be related to ethnicity (Lindberg et al., 1997). These findings have led to the suggestion that raised concentrations of sialic acid from glycoproteins and the resultant acute phase response may underlie much of the metabolic clustering, including glucose intolerance (Pickup and Crook, 1998).

A better understanding of cytokine actions and interactions with other factors in the pathogenesis of type 2 diabetes may lead to improved understanding of its causes and open new approaches for its prevention.


This study was supported by IRPA grant No. 06-02-03-6112-EA612 from the Ministry of Science and Technology, Malaysia.

1:  Abdella, N., A. Akanji, O. Mojiminlyi, A. Assoussi and M. Moussa, 2000. Relationship of serum total sialic acid concentrations with diabetic complications and cardiovascular risk factors in Kuwaiti type 2 diabetics. Diabetes Res. Clin. Pract., 50: 65-72.

2:  Chambers, J.C., S. Eda, P. Basset, Y. Karim and S.G. Thompson et al., 2001. C-Reactive Protein, Insulin resistance, central obesity and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation, 104: 145-150.

3:  Crook, M.A., L. Goldsmith, P. Ameerally, P. Lumb and N. Singh et al., 2002. Serum sialic acid, a possible cardiovascular risk factor is not increased in Fijian Melanesian with impaired glucose tolerance or impaired fasting glucose. Ann. Clin. Biochem., 39: 606-608.
Direct Link  |  

4:  Festa, A., R. D’Agostino, G. Howard, L. Mykkanen, R.P. Tracy and S.M. Haffner, 2000. Chronic subclinical inflammation as part of the insulin resistance syndrome: The Insulin Resistance Atherosclerosis Study (IRAS). Circulation, 102: 42-47.
CrossRef  |  Direct Link  |  

5:  Freeman, D.J., J. Norrie, M.J. Casslake, A. Gaw and I. Ford et al., 2002. C-reactive protein is an independent predicator of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes, 51: 1596-1600.
Direct Link  |  

6:  Frohlich, M., A. Imhof, G. Berg, W.L. Hutchinson and M.B. Pepys et al., 2000. Association between C-reactive protein and features of the metabolic syndrome: A population-based study. Diabetes Care, 23: 1835-1839.

7:  Jarrett, R.J. and M.J. Shipley, 1988. Type 2 (non-insulin-dependent) diabetes mellitus and cardiovascular disease: Putative association via common antecedents-further evidence from the whitehall sxtudy. Diabetologia, 31: 737-740.

8:  Jourdian, G.W., D. Lawrence and S.A. Roseman, 1971. A periodate resorcinol method for the quantitative estimation of free sialic acids and their glycosides. J. Biol. Chem., 246: 430-435.

9:  Koenig, W., M. Sund, M. Frohlich, H.G. Fischer and H. Lowe et al., 1999. C- reactive protein a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle aged men: Results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) augsburg cohort study, 1984 to 1992. Circulation, 99: 237-424.

10:  Lagrand, W.K., C.A. Visser, W.T. Hermens, H.W.M. Niessen and F.W.A. Verheugt et al., 1999. C-reactive protein as a cardiovascular risk factor: More than an epiphenomenon? Circulation, 100: 96-102.
Direct Link  |  

11:  Lindberg, G., G.A. Eklund, B. Gullberg and L. Rastam, 1991. Serum sialic acid concentration and cardiovascular mortality. Br. Med. J., 302: 143-146.
Direct Link  |  

12:  Lindberg, G., L. Rastam, B. Gulberg, A. Lundblad, P. Nilsson-Ehle and B.S. Hanson, 1993. Serum concentrations of total sialic acid and sialoglycoproteins in relation to coronary heart disease risk markers. Atherosclerosis, 103: 123-129.
Direct Link  |  

13:  Lindberg, G., H. Iso, L. Rastam, A. Lundblad and A.R. Folsom, 1997. Serum sialic acid and its correlate in community samples from Akita, Japan and Minneapolis. USA. Int. J. Epidemiol., 26: 58-63.
Direct Link  |  

14:  Maseri, A., 1977. Inflammation, atherosclerosis and ischeamic events. Exploring the hidden side of the moon. N. Eng. J. Med., 336: 1014-1016.

15:  Nayak, B.S. and L. Roberts, 2006. Relationship between inflammatory markers, metabolic and anthropometric variables in the Caribbean type 2 diabetic patients with and without microvascular complications. J. Inflamm., Vol. 3. 10.1186/1476-9255-3-17

16:  Ng, S.S. and J.A. Dain, 1976. The Natural Occurrence of Sialic Acids. In: Biological Roles of Sialic Acid, Rosendberg, A. and C.L. Schengrund (Eds.). Plenum Press, New York, pp: 59-102.

17:  Pickup, J.C., M.B Mattock, G.D. Chusney and D. Burt, 1997. NIDDM as a disease of the innate immune system: Association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia, 40: 1286-1292.

18:  Pickup, J.C. and M.A. Crook, 1998. Is type II diabetes mellitus a disease of the innate immune system. Diabetologia, 41: 1241-1248.

19:  Pickup, J.C., 2004. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care, 27: 813-823.
CrossRef  |  Direct Link  |  

20:  Reaven, G.M., 1988. Role of insulin resistance in human disease. Diabetes, 37: 1595-1607.
CrossRef  |  PubMed  |  Direct Link  |  

21:  Ross, R., 1999. Atherscelerosis-an inflammatory disease. N. Eng. J. Med., 340: 115-126.

22:  Salhanick, A.I. and J.M. Amatruda, 1988. Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus. Am. J. Physiol. Endocrind. Metab., 255: E173-E179.

23:  Schmidt, M.I., R.L. Watson, B.B. Duncan, P. Metcalf and F.L. Brancati et al., 1996. Clustering of dyslipidemia, hyperuricemia, diabetes and hypertension and its association with fasting insulin and central and overall obesity in a general population. Metabolism, 45: 699-706.
Direct Link  |  

24:  Schmidt, M.I., B.B. Duncan, A.R. Sharrett, G. Lindberg and P. J. Savage et al., 1999. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities Study): A cohort study. Lancet, 353: 1649-1652.

25:  Stern, M.P., 1995. Diabetes and cardiovascular disease: the common soil hypothesis. Diabetes, 44: 369-374.

26:  Wajchenberg, B.L., D.A. Malerbi, M.S. Rocha, A.C. Lerario and A.T. Santomauro, 1994. Syndrome X: A syndrome of insulin resistance. Epidemiological and clinical evidence. Diabetes Metab. Rev., 10: 19-29.

27:  Yudkin, J., 1997. Is insulin vasculotoxic? Diabetologia, 40: S140-S146.

©  2021 Science Alert. All Rights Reserved