Insulin resistance as a determinant of platelet activation in obese women.
OBJECTIVE
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 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 metabolite excretion as a non-invasive index of platelet activation. An index of insulin sensitivity, S(I), and plasma adiponectin, C-reactive protein (CRP), and CD40 ligand (CD40L) levels were measured.


RESULTS
Obese women had significantly (p < 0.0001) higher 11-dehydro-thromboxane B2 (11-dehydro-TXB2) excretion (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 S(I) (median 2.51 vs. 5.0 10(4) min(-1)/[microU/ml], p < 0.002) and adiponectin (6.3 vs. 10 microg/ml, p < 0.01) than control subjects. On multiple regression analysis, waist-to-hip ratio (beta = 0.27, p < 0.05) and S(I) (beta = -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 pioglitazone treatment on urinary 11-dehydro-TXB2 in 10 women with impaired S(I) and visceral obesity. Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with increased S(I) (+92%) and decreased 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) without changes in body weight.


CONCLUSIONS
Insulin resistance is a major determinant of platelet activation in female obesity.
Basili
Stefania
S
Department of Medical Therapy, University of Rome La Sapienza, Rome, Italy.
Pacini
Giovanni
G
Guagnano
Maria Teresa
MT
Manigrasso
Maria Rosaria
MR
Santilli
Francesca
F
Pettinella
Caterina
C
Ciabattoni
Giovanni
G
Patrono
Carlo
C
Davì
Giovanni
G
D000328:Adult; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000276:immunology*; D008875:Middle Aged; D009765:Obesity / Q000276:immunology*; D015539:Platelet Activation / Q000276:immunology*; D013929:Thromboxane B2 / Q000652:urine
D013929:Thromboxane B2