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.
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 alpha1-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 alpha1-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.
Schalkwijk
C G
CG
Department of Clinical Chemistry, Haematology and Internal Medicine, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Poland
D C
DC
van Dijk
W
W
Kok
A
A
Emeis
J J
JJ
Dräger
A M
AM
Doni
A
A
van Hinsbergh
V W
VW
Stehouwer
C D
CD
D000328:Adult; D000419:Albuminuria; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology* / Q000652:urine; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007249:Inflammation; D008297:Male; D009961:Orosomucoid / Q000032:analysis; D010741:Phospholipases A / Q000097:blood; D012016:Reference Values; D012044:Regression Analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D002097:C-Reactive Protein; D019040:E-Selectin; D005340:Fibrinogen; D006442:Glycated Hemoglobin; D009961:Orosomucoid; D010741:Phospholipases A; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor