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Plasma concentration of C-reactive protein is increased in Type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation
Authors:C G Schalkwijk  D C W Poland  W van Dijk  A Kok  J J Emeis  A M Dräger  A Doni  V W M van Hinsbergh  C D A Stehouwer
Institution:(1) Department of Clinical Chemistry, Haematology and Internal Medicine, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands, NL;(2) Department of Medical Chemistry, Institute for Immunology and Inflammatory Diseases, Vrije Universiteit, Amsterdam, The Netherlands, NL;(3) Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands, NL;(4) Istituto di Ricerche Farmacologiche ’Mario Negri', Milan, Italy, IT;(5) Gaubius Laboratory TNO-PG, Leiden, The Netherlands, NL
Abstract:Summary Moderately increased plasma concentrations of C-reactive protein are associated with an increased risk of cardiovascular disease. C-reactive protein, its relation to a low degree of inflammatory activation and its association with activation of the endothelium have not been systematically investigated in Type I (insulin-dependent) diabetes mellitus. C-reactive protein concentrations were measured in 40 non-smoking patients with Type I diabetes without symptoms of macrovascular disease and in healthy control subjects, and in a second group of Type I diabetic patients (n = 60) with normo- (n = 20), micro- (n = 20) or macroalbuminuria (n = 20). Differences in glycosylation of α1-acid glycoprotein were assayed by crossed affinity immunoelectrophoresis. Activation of the endothelium was measured with plasma concentrations of endothelial cell markers. The median plasma concentration of C-reactive protein was higher in Type I diabetic patients compared with healthy control subjects 1.20 (0.06–21.64) vs 0.51 (0.04–9.44) mg/l; p < 0.02]. The Type I diabetic subjects had a significantly increased relative amount of fucosylated α1-acid glycoprotein (79 ± 12 % vs 69 ± 14 % in the healthy control subjects; p < 0.005), indicating a chronic hepatic inflammatory response. In the Type I diabetic group, log(C-reactive protein) correlated significantly with von Willebrand factor (r = 0.439, p < 0.005) and vascular cell adhesion molecule-1 (r = 0.384, p < 0.02), but not with sE-selectin (r = 0.008, p = 0.96). In the second group of Type I diabetic patients, increased urinary albumin excretion was associated with a significant increase of von Willebrand factor (p < 0.0005) and C-reactive protein (p = 0.003), which were strongly correlated (r = 0.53, p < 0.0005). Plasma concentrations of C-reactive protein were higher in Type I diabetic patients without (clinical) macroangiopathy than in control subjects, probably due to a chronic hepatic inflammatory response. The correlation of C-reactive protein with markers of endothelial dysfunction suggests a relation between activation of the endothelium and chronic inflammation. Diabetologia (1999) 42: 351–357] Received: 4 September 1998 and in final revised form: 24 November 1998
Keywords:Type I (insulin-dependent) diabetes mellitus  acute-phase response  C-reactive protein  atherosclerosis  inflammation  vascular disease  α  1-acid glycoprotein  fucosylation  
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