Abnormalities of coagulation and fibrinolysis in insulin resistance - Evidence for a common antecedent?

Insulin resistance is associated not only with the classic cardiovascular r isk factors of hypertension and dyslipidemia, but also with several disorde rs of coagulation and fibrinolysis. Elevated concentrations of the fibrinol ytic inhibitor plasminogen activator inhibitor-1 are associated with insuli n resistance. In experimental systems, increased expression and secretion o f plasminogen activator inhibitor-1 by hepatocyte and endothelial cell line s can be induced by insulin, proinsulin-like molecules, triglyceride-rich l ipoproteins and oxidized LDL, as well as by inducing insulin resistance in isolated hepatocytes. Concentrations of the endothelial cell protein von Wi llebrand factor are elevated in insulin-resistant states, suggesting that a bnormalities of capillary endothelium, as well as those reported for endoth elium-dependent vasodilatation, may play a role in the etiology of insulin resistance. Levels of a third coagulation factor, fibrinogen, are elevated in insulin-resistant subjects, an association that suggests a possible role for acute-phase cytokines in the abnormalities of coagulation and endothel ial function. It is proposed that the recent observations of secretion of i nterleukin-6 by adipose tissue, combined with the actions of adipose tissue -expressed tumor necrosis factor-cr in obesity-induced insulin resistance, could underlie the associations of insulin resistance with endothelial dysf unction, coagulopathy and coronary heart disease.