Association between increased platelet P-selectin expression and obesity in patients with type 2 diabetes: a BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) substudy

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 nine 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 micromol/l 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 microm 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 A1C (P < 0.04), was not related to the concentration of triglycerides in blood, and did not correlate with the concentration of C-reactive peptide. CONCLUSIONS Among patients enrolled in this substudy 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.

Figure 1

Distribution of platelet activation in response to ADP. The activation of platelets induced by 0.2 μmol/l ADP and 1 μmol/l ADP was quantified with the use of flow cytometry based on the surface expression of P-selectin or the binding of fluorochrome-labeled fibrinogen. Each box plot of the distribution of the percentage of platelets activated shows the median (line), the 25th and 75th percentile (box), and the 10th and 90th percentile (error bars).

Figure 2

Correlation between the activation of platelets identified by the surface expression of P-selectin in response to 1 μmol/l ADP and BMI in patients with diabetes. Because the activation of platelets was not normally distributed, the results were log transformed. Pearson correlation coefficient and P value are shown. The inset is a box plot showing the distribution of platelet activation in patients with a lean BMI (<25 kg/m²), overweight patients (BMI 25–30 kg/m²), obese patients (BMI 30–35 kg/m²), and morbidly obese patients (>35 kg/m²). A stepwise increment was seen with increasing BMI (P < 0.02).