Original research| Volume 8, ISSUE 4, P352-357, December 2014

Download started.


Sialic acid and incidence of hospitalization for diabetes and its complications during 40-years of follow-up in a large cohort: The Värmland survey


      • Inflammatory markers predict incident type-2 diabetes.
      • Inflammation plays a role for the development of diabetes complications.
      • The association between sialic acid and incident diabetes has been studied.
      • 87,035 men and women have been followed-up in national registers.
      • Sialic acid is independently associated with risk of incident diabetes.



      To examine the association of sialic acid (SA) with first recorded diabetes mellitus-related hospitalization.


      From a population-based study in Värmland, Sweden, between 1962 and 1965, 87,035 men and women were selected and followed for first recorded diabetes-related hospitalization until 2005. The association of SA was calculated and stratified for gender by Cox's proportional hazards models. Adjustments were made for conventional risk factors and socioeconomic status. Association analyses were made for comparisons between SA-levels above and below median.


      The mean age was 47.2 (SD 13.0) years and the total numbers of incident diabetes-related hospitalizations in men and women were 3445 and 3273, respectively. Hazard ratios per one standard deviation of SA were 1.12 (95% CI: 1.08–1.17, p < 0.0001) in men and 1.17 (95% CI: 1.13–1.22, p < 0.0001) in women. Interaction analyses indicated a relatively higher SA-associated risk in women than in men with above median SA levels.


      In this large population-based cohort followed for more than 40 years, elevated SA, as a marker of systemic inflammation, was independently associated with risk of diabetes and diabetes-related hospitalizations.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Primary Care Diabetes
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wannamethee S.G.
        • Lowe G.D.
        • Rumley A.
        • et al.
        Adipokines and risk of type 2 diabetes in older men.
        Diabetes Care. 2007; 30: 1200-1205
        • Belin de Chantemele E.J.
        • Stepp D.W.
        Influence of obesity and metabolic dysfunction on the endothelial control in the coronary circulation.
        J. Mol. Cell. Cardiol. 2012 Apr.; 52 (Epub 2011 Aug 26): 840-847
        • Tilg H.
        • Moschen A.R.
        Inflammatory mechanisms in the regulation of insulin resistance.
        Mol. Med. 2008; 14: 222-231
        • Lee C.C.
        • Adler A.I.
        • Sandhu M.S.
        • et al.
        Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis.
        Diabetologia. 2009; 52: 1040-1047
        • Herder C.
        • Baumert J.
        • Zierer A.
        • et al.
        Immunological and cardiometabolic risk factors in the prediction of type 2 diabetes and coronary events: MONICA/KORA Augsburg case-cohort study.
        PLoS ONE. 2011; 6: e19852
        • Petren S.
        • Vesterberg O.
        The N-acetylneuraminic acid content of five forms of human transferrin.
        Biochim. Biophys. Acta. 1989; 994: 161-165
        • Sathiyapriya V.
        • Selvaraj N.
        • Nandeesha H.
        • et al.
        Association between protein bound sialic acid and high sensitivity C-reactive protein in prehypertension: a possible indication of underlying cardiovascular risk.
        Clin. Exp. Hypertens. 2008; 30: 367-374
        • Dogan H.
        • Pasaoglu H.
        • Ekinciler O.F.
        • Tatlisen N.
        A comparative study of total protein, total and lipid associated serum sialic acid levels in patients with Behcet's disease and control groups.
        Acta Ophthalmol. 1992; 70 (Copenh.): 790-794
        • Sillanaukee P.
        • Ponnio M.
        • Jaaskelainen I.P.
        Occurrence of sialic acids in healthy humans and different disorders.
        Eur. J. Clin. Invest. 1999; 29: 413-425
        • Lindberg G.
        • Rastam L.
        • Gullberg B.
        • Eklund G.A.
        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
        • Rahman I.U.
        • Malik S.A.
        • Bashir M.
        • et al.
        Serum sialic acid changes in type 2 diabetic patients on metformin or rosiglitazone treatment.
        J. Clin. Pharm. Ther. 2010; 35: 685-690
        • Thorand B.
        • Baumert J.
        • Kolb H.
        • et al.
        Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002.
        Diabetes Care. 2007; 30: 854-860
        • Salomaa V.
        • Havulinna A.
        • Saarela O.
        • et al.
        Thirty-one novel biomarkers as predictors for clinically incident diabetes.
        PLoS ONE. 2010; 5: e10100
        • Socialstyrelsen
        The Värmland Survey.
        Socialstyrelsen, Stockholm1971
      1. Health screening project in Värmland: a pilot study on mass screening with application of a chemical test battery.
        in: Jungner G. Jungner I. 14th Session of the Regional Committee for Europe of the WHO. Swedish National Board of Health, Prague1964
        • Svennerholm L.
        Quantitative estimation of sialic acids. II. A colorimetric resorcinol–hydrochloric acid method.
        Biochim. Biophys. Acta. 1957; 24: 604-611
        • Zak B.
        • Dickenman R.C.
        • White E.G.
        • et al.
        Rapid estimation of free and total cholesterol.
        Am. J. Clin. Pathol. 1954; 24: 1307-1315
        • Jungner G.
        • Jungner I.
        Chemical health screening.
        in: Sharp C.L.E.H. Keen H. Presymptomatic Detection and Early Diagnosis: A Critical Appraisal. Pitman Medical Publishing Corporation, London1968: 67-108
        • Reitman S.
        • Frankel S.
        A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases.
        Am. J. Clin. Pathol. 1957; 28: 56-63
        • Karmen A.
        A note on the spectrometric assay of glutamic–oxalacetic transaminase in human blood serum.
        J. Clin. Invest. 1955; 34: 131-133
        • Rothman K.
        Epidemiology: An Introduction.
        Oxford University Press, New York2002
        • Andersson T.
        • Alfredsson L.
        • Kallberg H.
        • et al.
        Calculating measures of biological interaction.
        Eur. J. Epidemiol. 2005; 20: 575-579
        • Huxley R.
        • Barzi F.
        • Woodward M.
        Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies.
        Br. Med. J. 2006; 332: 73-78
        • Lee W.L.
        • Cheung A.M.
        • Cape D.
        • Zinman B.
        Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies.
        Diabetes Care. 2000; 23: 962-968
        • Steinberg H.O.
        • Paradisi G.
        • Cronin J.
        • et al.
        Type II diabetes abrogates sex differences in endothelial function in premenopausal women.
        Circulation. 2000; 101: 2040-2046
        • Donahue R.P.
        • Rejman K.
        • Rafalson L.B.
        • et al.
        Sex differences in endothelial function markers before conversion to pre-diabetes: does the clock start ticking earlier among women? The Western New York Study.
        Diabetes Care. 2007; 30: 354-359
        • Mendall M.A.
        • Patel P.
        • Asante M.
        • et al.
        Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.
        Heart. 1997; 78: 273-277
        • Sattar N.
        Biomarkers for diabetes prediction, pathogenesis or pharmacotherapy guidance? Past, present and future possibilities.
        Diabet. Med. 2012; 29: 5-13
        • Schmidt M.I.
        • Duncan B.B.
        • Sharrett A.R.
        • et al.
        Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): a cohort study.
        Lancet. 1999; 353: 1649-1652
        • Hara S.
        • Yamaguchi M.
        • Takemori Y.
        • et al.
        Determination of mono-O-acetylated N-acetylneuraminic acids in human and rat sera by fluorometric high-performance liquid chromatography.
        Anal. Biochem. 1989; 179: 162-166
        • Crook M.
        • Collins D.
        • Lumb P.
        • et al.
        The relationship between the female menopause and serum sialic acid, a known cardiovascular risk factor.
        Eur. J. Obstet. Gynecol. Reprod. Biol. 1998; 76: 185-187