Relative Contribution of Insulin and Its Precursors to Fibrinogen and PAI-1 in a Large Population With Different States of Glucose Tolerance

Abstract

—Hyperinsulinemia is associated with the development of coronary heart disease. However, the underlying mechanisms are still poorly understood. Hypercoagulability and impaired fibrinolysis are possible candidates linking hyperinsulinism with atherosclerotic disease, and it has been suggested that proinsulin rather than insulin is the crucial pathophysiological agent. The aim of this study was to investigate the relationship of insulin and its precursors to markers of coagulation and fibrinolysis in a large triethnic population. A strong and independent relationship between plasminogen activator inhibitor-1 (PAI-1) antigen and insulin and its precursors (proinsulin, 32-33 split proinsulin) was found consistently across varying states of glucose tolerance (PAI-1 versus fasting insulin [proinsulin], r=0.38 [r=0.34] in normal glucose tolerance; r=0.42 [r=0.43] in impaired glucose tolerance; and r=0.38 [r=0.26] in type 2 diabetes; all P<0.001). The relationship remained highly significant even after ac...