PLASMINOGEN-ACTIVATOR INHIBITOR-1 ACTIVITY IS INDEPENDENTLY RELATED TO BOTH INSULIN SENSITIVITY AND SERUM TRIGLYCERIDES IN 70-YEAR-OLD MEN

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have bee n discussed as a part of the insulin resistance syndrome. However, it is not clear whether the relationship between PAI-1 and insulin resist ance is independent of or mediated by increased triglycerides levels, The aim of this study was to investigate whether PAI-1 activity is ass ociated with insulin sensitivity independently of serum triglycerides (sTG) and of other potential confounders, Seventy year old men (n=871) , participating in a cohort study undergoing extensive metabolic inves tigations, had blood samples taken for determination of PAI-1 activity . Insulin sensitivity was determined by the euglycemic hyperinsulinemi c clamp. In multivariate correlation and regression analyses, insulin sensitivity was a statistically significant determinant of PAI-1 activ ity (partial r=-.12, P<.001), independent of sTG, body mass index, wai st-hip ratio, and other potential confounders. The levels of sTG were also independently related to PAI-1 activity (partial r=.18; P<.001), The relationships between PAI-1 and insulin sensitivity and sTG were i ndependent of fasting glucose levels. Aggregation of risk factors of t he insulin resistance syndrome was associated with increased activity of PAI-1 in men with normal glucose tolerance, We conclude that PAI-1 activity is related to insulin sensitivity and sTG, independently of e ach other and of other potential confounders, and that increased level s of PAI-1 should be regarded as a component of the insulin resistance syndrome.