title: Meal-induced platelet activation in Type 2 diabetes mellitus: effects of treatment with repaglinide and glibenclamide.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Clinical Pharmacology Unit, Karolinska Hospital, Stockholm, Sweden. yngen@medks.ki.se
authors.forename: M
authors.initials: M
authors.lastname: Yngen
authors.forename: C-G
authors.initials: CG
authors.lastname: Ostenson
authors.forename: P
authors.initials: P
authors.lastname: Hjemdahl
authors.forename: N H
authors.initials: NH
authors.lastname: Wallén
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D002219:Carbamates / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004435:Eating / Q000502:physiology*; D005215:Fasting; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000032:analysis; D010880:Piperidines / Q000627:therapeutic use*; D015539:Platelet Activation / Q000502:physiology*; D010979:Platelet Function Tests / Q000379:methods; D019518:Postprandial Period; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D019007:P-Selectin; D010880:Piperidines; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D000244:Adenosine Diphosphate; C072379:repaglinide; D002097:C-Reactive Protein; D005905:Glyburide