Plasminogen Activator Inhibitor-1 Activity Is Independently Related to Both Insulin Sensitivity and Serum Triglycerides in 70-Year-Old Men

From the Department of Geriatrics (L. Byberg, L. Berglund, R.R., H.L.) and the Department of Clinical Chemistry (A.S.), Uppsala University, Sweden; and the Department of Epidemiology and Population Sciences, London School of Hygiene and Tropical Medicine, UK (P.M.).

Correspondence to Liisa Byberg, Department of Geriatrics, Uppsala University, PO Box 609, S-751 25 Uppsala, Sweden. E-mail liisa.byberg{at}geriatrik.uu.se

Abstract—Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been discussed as a part of the insulin resistance syndrome. However, it is not clear whether the relationship between PAI-1 and insulin resistance is independent of or mediated by increased triglycerides levels. The aim of this study was to investigate whether PAI-1 activity is associated 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 investigations, had blood samples taken for determination of PAI-1 activity. Insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp. In multivariate correlation and regression analyses, insulin sensitivity was a statistically significant determinant of PAI-1 activity (partial r=-.12; P<.001), independent of sTG, body mass index, waist-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 independent of fasting glucose levels. Aggregation of risk factors of the 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 each other and of other potential confounders, and that increased levels of PAI-1 should be regarded as a component of the insulin resistance syndrome.

Key Words: plasminogen activator inhibitor-1 • insulin sensitivity • triglycerides • hyperglycemia • cardiovascular disease

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