Abstract

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO_x) were 34.0 ± 4.9 μmol/l in the control subjects and 52.4 ± 5.1, 50.0 ± 5.1, and 49.0 ± 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 ± 2.0 μmol/l in the control subjects and 26.8 ± 4.4, 26.1 ± 4.3, and 32.7 ± 4.3 in the diabetic patients (P < 0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score −0.522 ± 0.25 versus 0.273 ± 0.22; P < 0.025). Patients with high NO_x had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.