Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin‐dependent diabetic patients: relation with platelet aggregation and with microangiopatic complications

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Abstract
Reduced glutathione (GSH) and activity of GSH related enzymes play a key role in defence against oxygen free radicals, whose production is, as known, raised in patients affected by diabetes mellitus, and at the same time they may contribute to the process of platelet aggregation. The purpose of this study was to evaluate GSH levels and activity of glutathione peroxidase (GSH‐Px), glutathione reduc‐tase (GSSG‐Red), glutathione transferase (GSH‐Tr), glucose‐6‐phosphate‐dehydrogenase (G6PDH), and thioltransferase (TT) in platelets of insulin‐dependent diabetic patients in fair metabolic control (mean glycated haemoglobin: 6.5%), as related to presence of retinopathy, neuropathy or nephropathy and to platelet aggregation by arachidonic acid (AA)in vitro. Mean effective dose (ED50) of AA was on average significantly lower in the group of insulin‐dependent diabetic patients (0.41 ± 0.02mM (SEM),n= 46) as compared with that of control subjects strictly matched for age, sex and weight (0.77 ± 0.02, n= 51; P= 0.0001). Mean platelet GSH as well as the activity of GSH related enzymes expressed as geometric mean (95% confidence intervals) were similar in diabetic patients and in controls, except for GSSG‐Red whose activity was significantly higher in diabetic subjects (28.5 (14.4–57.5) mU 10‐9 platelets vs. 20.3 (8.7–56) mU 10‐9 platelets; P= 0.01). In the diabetic group TT was reduced when compared with healthy controls (3.8 (0.9–12.2) mU 10‐9 platelets vs. 6 (1.6–26.1) mU 10‐9 platelets; P = 004). Moreover TT was significantly reduced in diabetic patients with worse metabolic control or with increased urinary albumin excretion rate (AER ≤ 20 μg min‐1), while neither TT, GSH nor GSH related enzymes were significantly different in patients with retinopathy or neuropathy. In addition TT was significantly related to ED50 of AA (r= 0.51; P= 0.0003). In conclusion GSH is not modified in insulin‐dependent diabetic patients in fair metabolic control, probably due to an augmented GSSG‐Red activity. Diabetic status, increase in platelet aggregation, and raised urinary AER seem to be altogether associated with a selective reduction in platelet TT activity.