Abstract 265: Insulin Resistance as a Determinant of Platelet Activation in Obese Women
Objectives: We tested the hypothesis that insulin resistance per se contributes to increased platelet activation in obesity, independently of underlying inflammation.
Background: Obesity, insulin resistance, and atherosclerosis are closely linked phenomena, often associated with low-grade inflammation. Obesity is associated with persistent platelet activation in otherwise healthy women.
Methods: We performed a cross-sectional study in 40 obese and 20 non-obese healthy women using urinary thromboxane (TX) metabolite excretion as a non-invasive index of platelet activation. An index of insulin sensitivity, SI, was calculated and plasma adiponectin, C-reactive protein (CRP) and CD40 ligand (CD40L) levels were also measured.
Results: Obese women had significantly (p<0.0001) higher 11-dehydro-TXB2 excretion rate (median 718 vs. 211 pg/mg/creatinine), CRP (1.13 vs. 0.48 mg/L) and CD40L levels (4.45 vs. 0.90 ng/mL) than controls. Obese women had lower SI (median 2.51 vs. 5.0 104 min−1/(μU/mL), (p<0.002) and adiponectin (6.3 vs. 10 μg/mL, p<0.01) than controls. On multiple regression analysis waist-to-hip ratio (β = 0.27, p<0.05) and SI (β = -0.72, p<0.04) predicted 11-dehydro-TXB2 excretion rate, independently of adiponectin, CRP, CD40L, and lipid patterns. In order to investigate the cause-effect relationship of these associations, we examined the effects of a 12-week weight loss program or a 3-week treatment with pioglitazone on urinary 11-dehydro-TXB2 in 10 women with impaired SI and visceral obesity. Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with an increase in SI (+92%) and a decrease in CD40L (-27%), CRP (-37%) and 11-dehydro-TXB2 (-53%), (p<0.05). Consistently, improvement of insulin sensitivity achieved with pioglitazone significantly decreased urinary 11-dehydro-TXB2 excretion (-43%; p<0.05) with no change in body weight.
Conclusions: insulin resistance is a major determinant of platelet activation in female obesity.