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

ABSTRACT

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 HbA1c 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 HbA1c>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.