Fibrinolysis and Diabetic Retinopathy in NIDDM

Abstract

OBJECTIVE By contributing to a prothrombotic state, increased levels of plasminogen activator inhibitor-1 (PAI-1) may be involved in the pathogenesis of the vascular complications of non-insulin-dependent diabetes mellitus (NIDDM). The objective of this study was to compare levels of components of the fibrinolytic system in NIDDM subjects with and without retinopathy. RESEARCH DESIGN AND METHODS A total of 135 Caucasian NIDDM subjects treated with oral therapy or diet alone were classified by the presence or absence of retinopathy, and fasting blood samples were taken for assay of PAI-1 antigen and activity, tissue plasminogen activator (t-PA), t-PA complexed with PAI-1, euglobulin clot lysis time (a measure of overall fibrinolytic activity), glucose, HbA1c, cholesterol, triglyceride, and insulin levels. RESULTS Subjects with retinopathy had a longer disease duration than those without (9 vs. 5 years, P < 0.0001) and had lower levels of PAI-1 (PAI-1 antigen) (geometric mean and 95% confidence interval), 13.9 (10.4–18.6) vs. 24.1 (21.2–27.4) ng/ml (P < 0.0005); t-PA antigen, 9.6 (8.6–10.7) vs. 11.5 (10.8-12.3) ng/ml (P < 0.01); t-PA—PAI-1 complexes, 6.2 (5.2–7.2) vs. 7.8 (6.8–8.8) ng/ml (P < 0.05); and insulin, 11.5 (9.3-14.3) vs. 19.5 (17.0–22.3) mU/l (P < 0.0005). Euglobulin clot lysis time was shorter in the subjects with retinopathy, 273 (238–312) vs. 327 (303–352) min. When entered into a logistic regression model, disease duration, PAI-1 antigen, and HbA1c remained as significant independent associates of the presence of retinopathy. CONCLUSIONS These results do not support the hypothesis that impaired fibrinolysis due to elevated PAI-1 is associated with the development of retinopathy because fibrinolysis is indeed enhanced and PAI-1 lower in subjects with retinopathy.