MICRO ALBUMINURIA AS A RISK FACTOR FOR MACROVASCULAR DISEASE IN TYPE 2 DIABETES MELLITUS: THE ROLE OF PLASMINOGEN ACTIVATOR INHIBITOR-I (PAI-1)

Atherosclerosis is the most common complication of diabetes, particularly type 2 DM. Atherosclerotic vascular diseases, such as myocardial infarction, stroke and lower extremity arteriopathy account for up 60-70% of deaths in type 2 DM.The precise pathogenic mechanisms linking diabetes and atherosclerosis are still a matter of speculation. The procoagulant state observed in diabetic subjects has been proposed as a further potentially important pathophysiological link between diabetes, atherosclerosis and arterial thrombosis.Type 2 DM represent a prothrombotic state due to a dysbalance between procoagulant and antithrombotic factors and between activators and inhibitors of plasminogen activation.Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of fibrinolytic pathway and extracellular matrix (ECM) turnover, because diabetic nephropathy is characterized by the presence of basement membrane thickening and mesangial expansion.Albuminuria has been defined as a definite, independent risk factor for cardiovascular disease in type 2 diabetic patients.However, the link between albuminuria and atherosclerosis is still not clearly explained, different pathophysiological mechanisms have been suggested to link the two processes including; dyslipidaemia, abnormally higher levels of von-willbrand factor in microalbuminuric patients, raised homocystein levels in patients with microalbuminuria and impaired fibrinolysis.