Influence of glycaemic control on platelet bound CD40-CD40L system, P-selectin and soluble CD40 ligand in Type 2 diabetes

P>Aims Type 2 diabetes is a potent cardiovascular risk factor, associated with proinflammatory and prothrombotic processes. The purpose of this study was to investigate whether platelet-bound CD40-CD40L signalling, P-selectin expression and soluble CD40L were increased in patients with diabetes mellitus and can be normalized by improving glycaemic control. Methods Soluble (s) CD40L, platelet surface expression of CD40L, CD40 and P-selectin (CD62P) on platelets were measured by flow cytometry in 71 patients with Type 2 diabetes mellitus and 37 healthy volunteers. In addition, the relationship of HbA(1c) to CD40-CD40L and P-selectin expression was determined in a longitudinal follow-up. Results In patients with Type 2 diabetes, platelet membrane CD40 expression (Type 2 diabetes 3.1 +/- 0.61 vs. controls 2.5 +/- 0.85 mean fluorescence intensity; P = 0.001), platelet-bound CD40L (1.2 +/- 0.32 vs. 1.1 +/- 0.14; P = 0.034) as well as surface expression of CD62P (0.66 +/- 0.19 vs. 0.57 +/- 0.12; P = 0.007) were higher than in control subjects. Plasma sCD40L values (3.2 +/- 1.70 vs. 1.8 +/- 0.50 ng/ml; P < 0.001) were also significantly increased in Type 2 diabetes. After improving glycaemic control in patients with initial HbA(1c) > 8.5% (n = 15), platelet P-selectin and CD40-CD40L expression decreased significantly by 54.0%, 36.22% and 16.26%, respectively 1 year later. Conclusions Type 2 diabetes is associated with up-regulation of the platelet-bound CD40-CD40L system, platelet hyperactivity (enhanced P-selectin expression) and increased sCD40L levels. Improved glycaemic control, however, does help to correct abnormal platelet activation via down-regulation of CD40-CD40L system and P-selectin expression.