PROINSULIN, INTACT INSULIN, AND FIBRINOLYTIC VARIABLES AND FIBRINOGENIN HEALTHY-SUBJECTS - A POPULATION STUDY

OBJECTIVE - As high serum insulin predicts impaired fibrinolysis and p roinsulin reacts in most conventional insulin assays, we hypothesized that proinsulin could link low fibrinolytic activity and hyperinsuline mic conditions. RESEARCH DESIGN AND METHODS - We explored the relation ship between fibrinolysis and plasma fibrinogen on the one hand and sp ecific insulin and proinsulin on the other, in a healthy population sa mple of 165 men and women, 25-74 years of age, from the Northern Swede n MONICA (Monitoring of Trends and Determinants in Cardiovascular Dise ase) Study Specific insulin and proinsulin were measured by enzyme-lin ked immunosorbent assay. Partial correlation coefficients, adjusted fo r age and sex, were calculated. RESULTS - Plasma fibrinogen levels wer e related to insulin (r = 0.25, P < 0.01) and proinsulin (r = 0.29, P < 0.001), as was plasminogen activator inhibitor (PAI)-1 activity (r = 0.36 and r = 0.29, respectively; P < 0.001). Tissue plasminogen activ ator (tPA) activity correlated inversely to insulin (r = -0.35, P < 0. 001) and proinsulin (r = -0.36, P < 0.001). In a multivariate analysis taking also smoking and anthropometric and metabolic measurements int o account, fasting proinsulin was a significant predictor of high plas ma fibrinogen level. Insulin and proinsulin levels were not related to tPA activity. High levels of postload insulin, triglycerides, and dia stolic blood pressure, but not proinsulin, predicted high PAI-1 activi ty. CONCLUSIONS - In a healthy population, the relationship previously described between high insulin levels and impaired fibrinolysis is no t attributable to confounding from proinsulin. Elevated proinsulin lev els are associated with high fibrinogen levels.