Abnormal endothelial release of fibrinolytic activity and fibronectin in diabetic microangiopathy

Endothelial cell function in Type 1 (insulin-dependent) diabetic patients, both with and without retinopathy, was assessed by measuring the plasma fibrinolytic activity and fibronectin after 10 min venous stasis induced by a sphygmomanometer cuff. After venous stasis, diabetic subjects with proliferative retinopathy had fibrinolytic responses (median 0.13 increasing to 0.26 U/ml) in the low normal range, which were significantly less (p less than 0.005) than control subjects (0.17-0.68 U/ml) and diabetic patients with minimal retinopathy (0.16-0.68 U/ml; p less than 0.01). Plasma fibronectin levels were similar in the different groups, but after venous stasis, rose significantly in the diabetic patients, both in those with proliferative retinopathy (mean 317-399 micrograms/ml; p less than 0.002) and without retinopathy (312-371 micrograms/ml; p less than 0.05) but not in normal subjects (304-333 micrograms/ml). These changes in fibrinolytic activity and fibronectin were independent of blood glucose, glycosylated haemoglobin, or indices of sensory or autonomic nerve function. These disturbances of endothelial function, together with known abnormalities of haemostatic variables and microvascular reflexes, might convert a usually temporary obstruction of capillary blood flow into a pathological capillary closure, and might contribute to the inexorable progression of advanced diabetic microangiopathy in spite of good diabetic control.