Attenuated fibrinolysis and accelerated atherogenesis in type II diabetic patients.
Patients with hyperinsulinemia, defined by increased concentrations of IRI in plasma, experience increased cardiovascular mortality. In type II diabetic patients, the increase in IRI may reflect, in part, not only insulin but also proinsulinemia as a result of impaired conversion of proinsulin to insulin by pancreatic beta-cells. High IRI is accompanied by attenuation of endogenous fibrinolytic activity and increased plasma PAI-1, the primary physiological inhibitor of t-PA. Concordant increases of plasma PAI-1 and plasma IRI appear to reflect direct effects of insulin and proinsulin on the synthesis and secretion of PAI-1 by endothelial and liver cells as judged from results of studies in vitro. Because attenuated fibrinolysis may predispose to thrombosis, the increased exposure of luminal surfaces of vessels to atherogenic, clot-associated mitogens and chemoattractants may activate macrophages and potentiate proliferation of vascular smooth muscle cells. Accordingly, increased concentrations of plasma IRI may contribute to macrovascular disease in diabetic patients by impairing endogenous fibrinolysis.
Schneider
D J
DJ
Cardiovascular Division, Washington University School of Medicine, St. Louis, MO 63110.
Nordt
T K
TK
Sobel
B E
BE
D001161:Arteriosclerosis / Q000453:epidemiology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000503:physiopathology*; D005342:Fibrinolysis; D006801:Humans; D006946:Hyperinsulinism / Q000503:physiopathology; D007333:Insulin Resistance; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors
D017395:Plasminogen Activator Inhibitor 1