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

Abstract

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 (nϭ871), 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 rϭϪ.12; PϽ.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 rϭ.18; PϽ.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. (Arterioscler Thromb Vasc Biol. 1998;18:258-264.)Key Words: plasminogen activator inhibitor-1 Ⅲ insulin sensitivity Ⅲ triglycerides Ⅲ hyperglycemia Ⅲ cardiovascular disease N on-insulin-dependent diabetes mellitus has a high and increasing prevalence, especially in countries that are rapidly becoming affluent. In white and South Asian populations, NIDDM is associated with a twofold to threefold increase in cardiovascular disease.1 An early characteristic in the development of NIDDM is "insulin resistance," a state in which the promoting effect of insulin on glucose uptake is decreased. The "insulin resistance syndrome" comprises several cardiovascular risk factors, including elevated blood pressure, glucose intolerance, central obesity, and an atherogenic lipoprotein pattern characterized by elevated concentrations of plasma triglycerides, decreased HDL cholesterol, and increased levels of small, dense LDL particles.2 The insulin resistance syndrome is associated with an increased risk for cardiovascular disease, even at normoglycemia. 3 Although insulin has been associated with an increased risk of ischemic heart disease, 4 it is possible that elevated levels of the major rapid inhibitor of fibrinolysis in blood, PAI-1, is an important mediator of the increased incidence of cardiovascular disease in insulin-resistant states.5 Both insulin and triglyceride-rich lipoproteins stimulate the production of PAI-1 in cultured cells.6 -12 PAI-1 has been shown to be associated with insulin re...

Diabetes and Cardiovascular Disease

“…76 Patients with insulin resistance frequently manifest several alterations in coagulation mechanisms that predispose them to arterial thrombosis. These alterations include increased fibrinogen levels, 79 increased plasminogen activator inhibitor-1, 80 and various platelet abnormalities. 81 …”

Weight change and blood coagulability and fibrinolysis in healthy obese women

“…25,26 However, in vivo studies offer controversial results. Acute administration of insulin or triglycerides has 27,28 or has not increased PAI-1 activity in human studies. 29 ± 32 Con¯icting results may be due to pooling the results of men and women, small sample sizes, different methods, diverse dosages of insulin and short duration of euglycemic hyperinsulinaemia clamp studies.…”

Nonesterified Fatty Acids and Cardiovascular Mortality in Elderly Men with CKD

“…eGFR was also calculated by the CKD Epidemiology Collaboration (CKD-EPI) creatinine and cystatin C plus creatinine equations (CKD-EPI creatinine and CKD-EPI cystatin C+creatinine , respectively) (21), which were used in sensitivity analyses. Serum lipids and lipoproteins were detected as described previously (22). High-sensitivity C-reactive protein (CRP) was measured by a latex-enhanced reagent (Dade Behring, Deerfield, IL) using a Behring BN ProSpec analyzer (Dade Behring).…”