Contrasting Fibrinolytic Responses in Type 1 (Insulin‐dependent) and Type 2 (Non‐insulin‐dependent) Diabetes

To study fibrinolysis in relation to microvascular diabetic complications, 20 control subjects were compared with 50 Type 1 (insulin-dependent) diabetic patients of similar age, 20 with no complications, 17 with laser-treated retinopathy, and 13 with neuropathy and retinopathy. None were smokers, hypertensive or had macrovascular disease. Pre- and post-venous occlusion blood samples for tests of fibrinolysis were taken. Median (interquartile range) basal tissue plasminogen activator (t-PA) activity was lower in control subjects (100(<100–100) IU l−1) than diabetic patients (uncomplicated 145 (100–280) IU l−1, p = 0.015; retinopathy 180 (100–228) IU l−1, p = 0.037; neuropathy 210 (125–310) IU l−1, p = 0.004, respectively). Basal t-PA inhibition (PAI-1 activity) was higher in control subjects (5.9 (4.5–9.5) kIU l−1) than diabetic patients (uncomplicated 4.0 (3.3–5.0) kIU l−1, p = 0.001; retinopathy 4.5 (3.1–6.3) kIU l−1, p = 0.058; neuropathy 4.0 (3.0–5.4) kIU l−1, p = 0.015, respectively). Post-venous occlusion t-PA antigen was higher in control subjects (10.2 (7.3–15.1) μg l−1) than neuropathic patients (5.5 (4.9–7.3) μg l−1, p = 0.004). Other tests showed a consistent, but non-significant, trend towards increased basal fibrinolysis in the Type 1 diabetic patients. The results indicate that Type 1 diabetic patients have enhanced basal fibrinolysis. The diminished response to venous occlusion in neuropathic patients is consistent with an endothelial cell defect. These findings are in marked contrast to those in 20 uncomplicated Type 2 diabetic patients who had diminished basal and post-venous occlusion fibrinolytic activity with high basal t-PA (13.4 (9.8–16.8) μg l−1) and PAI-1 (26.5 (12.4–39.6) μg l−1) antigen. The differing fibrinolytic responses may contribute to the heterogeneous nature of vascular disease in diabetes.