Insulin sensitivity is not an independent determinant of plasma plasminogen activator inhibitor-1 activity.

Abstract

It recently has been hypothesized that increased plasma plasminogen activator inhibitor-1 (PAI-1) activity could be a possible link between insulin resistance and coronary heart disease. However, it is not known whether insulin sensitivity per se is a determinant of plasma PAI-1 activity or whether other intermediates could explain this association. We investigated the relationship between plasma PAI-1 activity and insulin sensitivity, obesity, distribution of body fat, blood pressure, plasma insulin concentration, and serum lipid levels in normoglycemic men (n = 61) and women (n = 77) 53 to 61 years old who participated in a previous population-based study. Insulin sensitivity was estimated by the minimal model from a frequently sampled intravenous glucose tolerance test. In univariate analyses, PAI-1 correlated positively with body mass index, waist-to-hip ratio (WHR), fasting and 2-hour insulin levels, and triglyceride level in both men and women. Furthermore, in women PAI-1 correlated inversely with high-density lipoprotein (HDL) cholesterol level. There was an inverse relationship between PAI-1 and insulin sensitivity (r = -.39, P < .01 in men; r = -.38, P < .001 in women). In multivariate analyses in men, insulin sensitivity failed to show any significant association with PAI-1. In contrast, triglyceride level and body mass index were independently associated with PAI-1. Also in women, insulin sensitivity was not independently associated with PAI-1. In women, WHR and HDL cholesterol concentration or WHR and 2-hour insulin concentration were independently related to PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)