M Yngen1, C-G Östenson2, H Hu3, N Li3, P Hjemdahl3, N H Wallén3,4. 1. Department of Medicine, Clinical Pharmacology Unit, Karolinska Hospital, 171 76, Stockholm, Sweden. marianne.yngen@ks.se. 2. Department of Molecular Medicine, Endocrine and Diabetes Unit, Karolinska Hospital, Stockholm, Sweden. 3. Department of Medicine, Clinical Pharmacology Unit, Karolinska Hospital, 171 76, Stockholm, Sweden. 4. Department of Internal Medicine, Danderyd University Hospital, Stockholm, Sweden.
Abstract
AIMS/HYPOTHESIS: Platelet activation, endothelial dysfunction and inflammation may be involved in early stages of diabetic microangiopathy. We therefore investigated patients with Type 1 diabetes mellitus, without ( n=19) and with ( n=20) microangiopathy, matched for glycaemic control and duration of disease, and matched with healthy control subjects ( n=27). METHODS: Platelet activation was measured as platelet P-selectin expression using whole blood flow cytometry and as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma, serum soluble E-selectin, CD40 ligand (sCD40L) and C-reactive protein (CRP) served as markers for endothelial function and inflammation. RESULTS: Thrombin-induced platelet P-selectin expression was enhanced, and soluble P-selectin and sCD40L concentrations were increased in patients with microangiopathy compared with the control subjects ( p<0.01 for both) and with patients without microangiopathy ( p<0.05 for P-selectin expression and sP-selectin), whereas all three parameters were similar in patients without microangiopathy and in the control subjects. CRP and soluble E-selectin were increased in patients with microangiopathy, compared with the control subjects ( p<0.01 and p<0.05), whereas von Willebrand factor did not differ between the groups. CONCLUSIONS/ INTERPRETATION: Microangiopathy in Type 1 diabetes is associated with platelet hyperactivity, endothelial dysfunction and low-grade inflammation, indicating an increased risk for cardiovascular disease.
AIMS/HYPOTHESIS: Platelet activation, endothelial dysfunction and inflammation may be involved in early stages of diabetic microangiopathy. We therefore investigated patients with Type 1 diabetes mellitus, without ( n=19) and with ( n=20) microangiopathy, matched for glycaemic control and duration of disease, and matched with healthy control subjects ( n=27). METHODS: Platelet activation was measured as platelet P-selectin expression using whole blood flow cytometry and as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma, serum soluble E-selectin, CD40 ligand (sCD40L) and C-reactive protein (CRP) served as markers for endothelial function and inflammation. RESULTS:Thrombin-induced platelet P-selectin expression was enhanced, and soluble P-selectin and sCD40L concentrations were increased in patients with microangiopathy compared with the control subjects ( p<0.01 for both) and with patients without microangiopathy ( p<0.05 for P-selectin expression and sP-selectin), whereas all three parameters were similar in patients without microangiopathy and in the control subjects. CRP and soluble E-selectin were increased in patients with microangiopathy, compared with the control subjects ( p<0.01 and p<0.05), whereas von Willebrand factor did not differ between the groups. CONCLUSIONS/ INTERPRETATION:Microangiopathy in Type 1 diabetes is associated with platelet hyperactivity, endothelial dysfunction and low-grade inflammation, indicating an increased risk for cardiovascular disease.
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