The relationship of oxidative stress to thrombotic tendency in type 1 diabetic patients with retinopathy

Increased free radical activity may contribute to thrombosis via effects on platelet aggregation and the prostanoid balance. To investigate this further we studied 15 Type 1 diabetic patients with retinopathy, matched with uncomplicated Type 1 patients for age, duration of diabetes and HbA¹, together with matched healthy non-diabetic control subjects. The oxidative effects of free radicals as total diene conjugates and lipid peroxides were measured, together with redox status extracellularly as plasma albumin-thiols and intracellularly as erythrocyte superoxide dismutase activity. Platelet count, aggregation of platelets in whole blood to collagen, thromboxane B₂, and prostacyclin stimulating factor (PGI₂SF) were also assessed. Free radicals measured as lipid peroxides were significantly higher (9.6 (8.1-11.6) µmol 1^-1 (median and interquartile range) in diabetic patients with retinopathy than in control subjects (8.1 (7.4-9.2) µmol 1^-1; p < 0.05). There were also significant reductions in redox status both extracellularly as plasma albumin thiols (408 (383-473) vs 490 (456-517) µmol 1^-1, p < 0.001) and intracellularly as erythrocyte superoxide dismutase activity (34 (27-41) vs 44 (36-51) g 1^-1, p < 0.05) between patients with retinopathy and control subjects. Platelet counts were increased in diabetic patients with retinopathy (p < 0.05), as was collagen-induced platelet aggregation (p < 0.01). Prostacyclin stimulating factor was reduced in patients with retinopathy (p < 0.05) and correlated within the plasma with lipid peroxides (r = -0.53, p < 0.04) and albumin thiols (r = 0.64, p < 0.01). The results suggest that diabetic patients, particularly with retinopathy, are under oxidative stress and have an increased thrombotic tendency with increased platelet reactivity and a reduction in prostacyclin stimulating factor.