Meal‐induced platelet activation in Type 2 diabetes mellitus: effects of treatment with repaglinide and glibenclamide

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Abstract
Aims  To compare the effects of treatment with repaglinide and glibenclamide on platelet function and endothelial markers in patients with Type 2 diabetes mellitus, before and after a standardized meal.Methods  Fifteen patients with Type 2 diabetes were investigated on three occasions: at baseline without oral hypoglycaemic drug treatment, and after 6 weeks’ treatment with repaglinide or glibenclamide, respectively, in an open randomized cross‐over study. Agonist‐induced platelet P‐selectin expression and platelet aggregation, urinary thromboxane, soluble P‐selectin, von Willebrand factor (VWF), soluble E‐selectin, intercellular adhesion molecule (ICAM‐1) and C‐reactive protein (CRP) were measured. In addition, pre‐meal data were compared with non‐diabetic control subjects (n = 15), matched for sex, age and BMI.Results  Adenosine diphosphate (ADP)‐induced platelet P‐selectin expression increased post‐meal in Type 2 diabetic patients both at baseline and after treatment with repaglinide and glibenclamide (P < 0.01 for all; repeated measures anova). Repaglinide treatment reduced fasting ADP‐induced P‐selectin expression compared with baseline (P = 0.01), but did not influence meal‐induced platelet hyper‐reactivity (P = 0.32). No significant anti‐platelet effects of glibenclamide treatment were found. Plasma concentrations of VWF and ICAM‐1 were elevated in patients with Type 2 diabetes compared with control subjects (P < 0.05 for both) and were reduced during treatment with repaglinide (P < 0.01 for both) but did not change during glibenclamide treatment.Conclusions  The post‐meal state is associated with enhanced platelet reactivity in patients with Type 2 diabetes mellitus. Pre‐meal treatment with repaglinide or glibenclamide does not inhibit postprandial platelet activation, but repaglinide treatment is associated with attenuated platelet and endothelial activity in the fasting state.