Association Between Increased Platelet P-Selectin Expression and Obesity in Patients With Type 2 Diabetes

Abstract

Objective: To determine whether obesity increases platelet reactivity and thrombin activity in patients with type 2 diabetes plus stable coronary artery disease. Research Design and Methods: We assessed platelet reactivity and markers of thrombin generation and activity in 193 patients from 9 clinical sites of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D). Blood taken at the time of enrollment was used for assay of the concentration of prothrombin fragment 1.2 (PT1.2, released when prothrombin is activated) and fibrinopeptide A (FPA, released when fibrinogen is cleaved). Platelet activation was identified with the use of flow cytometry in response to 0, 0.2, and 1 muM adenosine diphosphate (ADP). Results: Concentrations of FPA, PT1.2 and platelet activation in the absence of agonist were low. Greater BMI was associated with higher platelet reactivity in response to 1 mum ADP as assessed by surface expression of P-selectin (r=0.29, p<0.0001) but not reflected by the binding of fibrinogen to activated glycoprotein IIb-IIIa. BMI was not associated with concentrations of FPA or PT1.2. Platelet reactivity correlated negatively with HbA1C (p <0.04), was not related to the concentration of triglycerides in blood, and did not correlate with the concentration of CRP. Conclusions: Among patients enrolled in this sub-study of BARI 2D, a greater BMI was associated with higher platelet reactivity at the time of enrollment. Our results suggest that obesity and insulin resistance that accompanies obesity may influence platelet reactivity in patients with type 2 diabetes