Insulin resistance and alterations in the fibrinolytic system

Insulin resistance and the associated metabolic and haemodynamic abnormalities referred to as Syndrome 'X', are associated with an increased risk for the development of coronary artery disease. The exact reasons for this are not clearly understood with much current controversy surrounding the potential atherogenic effects of insulin. Under normal physiological conditions the fibrinolytic system is in a dynamic equilibrium with the coagulations process, and is responsible, via a series of activators and inhibitors, for controlled clot lysis. Depression of fibrinolytic activity due to increased levels of the main inhibitor plasminogen activator inhibitor-1 (PAI-1) has been shown to be elevated in certain disease states including coronary artery disease. In addition elevated levels of PAI-1 seem to be associated with the major individual features of Syndrome 'X'. The presence of elevated levels of PAI-1 in individuals with hyperinsulinaemia would help explain the increased frequency of coronary artery disease in those with features of the syndrome of insulin resistance. This article reviews the relationships between insulin, PAI-1 and the individual features of Syndrome 'X' and offers potential mechanisms by which insulin resistance may be linked to PAI-1.