Summary. Background: Platelets and leukocytes may in¯u-ence each others' function, i.e. platelet±leukocyte cross-talk. Diabetes mellitus (DM) is associated with platelet and leukocyte dysfunction. Objective: To evaluate platelet±leukocyte cross-talk, and if this might contribute to platelet and leukocyte dysfunction and microangiopathy in DM patients. Patients and methods: We evaluated platelet and leukocyte function, and cross-talk between these cells in Type 1 DM patients without (n 19) and with (n 20) microangiopathy, and healthy subjects (n 27), using whole blood¯ow cytometry. Platelet± leukocyte cross-talk was studied in hirudinized whole blood incubated at 37 8C with stirring. Results: Basal single platelet P-selectin and leukocyte CD11b expression were similar in DM patients and healthy subjects, whilst circulating platelet±leu-kocyte aggregates and plasma elastase levels were elevated in DM patients. The thromboxane A 2 analog U46619 (3 Â 10 À7 M) induced more marked increases of platelet P-selectin expression and platelet±leukocyte aggregation in DM patients than in healthy subjects. The leukocyte-speci®c agonist N-formylmethionyl-leucyl-phenylalanine (fMLP) (10 À7 M) induced more marked CD11b expression in DM patients with microangiopathy, compared with healthy subjects. Platelet±leukocyte cross-talk induced by U46619 (10 À6 M) showed no difference between DM patients and healthy subjects. fMLP (10 À6 M) evoked marked leukocyte activation, which subsequently caused mild platelet P-selectin expression. This leukocyte± platelet cross-talk was more pronounced in DM patients than in healthy subjects. Furthermore, enhanced leukocyte±platelet cross-talk was correlated to platelet hyperreactivity among DM patients with microangiopathy only. Conclusions: Type 1 DM is associated with platelet and leukocyte hyperactivity, and enhanced leukocyte±platelet cross-talk, which may contribute to platelet hyperactivity and the microvascular complications seen in Type 1 DM.

Summary. Background: Patients with Type 1 diabetes have a tighter plasma fibrin gel structure, to which impaired glycemic control might contribute. Improved glycemic control can be achieved with continuous subcutaneous insulin infusion (CSII). Objectives: The aim of the present study was to investigate the effect of CSII on plasma fibrin gel properties and circulating markers of inflammatory activity in patients with Type 1 diabetes. Patients and methods: Twenty-eight patients were investigated before and after 4-6 months' treatment with CSII. Fibrin gel structure formed in vitro from plasma samples was investigated by liquid permeation of hydrated fibrin gel networks. Pfibrinogen was analyzed by a syneresis method. Comparisons were made between patients with improved (> 0.5%) and unchanged (< 0.5%) glucosylated hemoglobin (HbA1c) during CSII. Results: Eighteen patients showed improved and 10 patients unchanged HbA 1c during CSII. P-fibrinogen, high sensitive C-reactive protein and serum amyloid A-antigen were not significantly changed, while fibrin gel permeability (Ks) and fiber mass-length ratio (m) increased in both groups (P < 0.02). P-insulin and triglycerides decreased (P < 0.05) in both groups, while reductions of total cholesterol and intercellular adhesion molecule-1 were seen only in patients with improved HbA 1c (P < 0.05). Absolute changes in Ks were inversely correlated to changes in plasma fibrinogen (r ¼ 0.50; P < 0.01) and in LDLcholesterol (r ¼ 0.46; P < 0.05). Conclusions: Treatment with CSII in patients with Type 1 diabetes is associated with increased plasma fibrin gel porosity. Slight attenuation of the inflammatory activity was also observed. The changes in fibrin gel porosity seem to be mainly mediated by changes in plasma fibrinogen and blood lipids, and are probably secondary to improved insulin sensitivity.

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