Comparison of plasminogen activator inhibitor-1 concentration in insulin-resistant versus insulin-sensitive healthy women

The primary goal of this investigation was to see whether plasminogen activ ator inhibitor-1 (PAI-1) concentrations varied as a function of differences in insulin-mediated glucose disposal in 2 groups of healthy women matched for every other variable that might play a role in regulation of PAI-1. For this purpose, we recruited 32 healthy women, divided on the basis of their steady-state plasma glucose (SSPG) concentrations during the insulin suppr ession test into an insulin-resistant (SSPG = 216 +/- 12 mg/dL, n = 16) and an insulin-sensitive (94 +/- 6 mg/dL, n = 16) group. PAI-1 antigen concent rations were significantly higher (26 +/- 4 versus 14 +/- 3 ng/mL, P < 0.02 ) in the insulin-resistant group. In addition, fasting plasma insulin (18 /- 3 versus 11 +/- 2 mu U/mL, P < 0.02) and triglyceride (160 +/- 19 versus 93 +/- 10 mg/dL, P < 0.001) concentrations were higher in the insulin-resi stant individuals, whereas HDL concentrations were lower (44 +/- 3 versus 5 8 +/- 3 mg/dL, P < 0.005). However, the 2 groups were essentially identical in terms of age, menopausal status, hormone replacement therapy, body mass index (BMI), ratio of waist-to-hip girth, and blood pressure. When the exp erimental population was considered as 1 group, there were statistically si gnificant correlations between PAI-1 antigen and the following variables: a djusting for differences in age and BMI, SSPG (r = 0.56, P < 0.001); trigly ceride (r = 0.39, P < 0.05); and HDL cholesterol (r = -0.65, P < 0.001) con centrations. Finally, multiple regression analysis revealed the major deter minants of PAI-1 to be insulin resistance, or insulin concentration, and HD L cholesterol. These results: 1) demonstrate that PAI-1 concentrations are higher in healthy, insulin-resistant women as compared with insulin-sensiti ve individuals, independent of differences in BMI or ratio of waist-to-hip girth; and 2) provide another mechanism by which insulin-resistant individu als are at increased thrombotic cardiovascular risk.