Oxidative stress and insulin requirements in patients with recent-onset type 1 diabetes

The purpose of this study was to analyze biochemical measures of oxidative stress and assess their relationship to insulin requirements early in type 1 diabetes. Thirty-seven patients enrolled in a 3-yr longitudinal study of the effects of oxidative stress on the early natural history of this disorder. We measured plasma nitrite and nitrate (collectively NOx), nitrotyrosine, and 8-iso-prostaglandin F-2alpha (8-iso-PGF(2alpha)). Plasma NOx was 34.0 +/- 4.9 mumol/liter in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 mumol/liter in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine was 13.3 +/- 2.0 mu mol/liter in controls and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 mu mol/liter in the diabetic patients (P < 0.01). 8-Iso-PGF(2alpha) was higher in the poorly controlled than in the well controlled patients. NOx correlated with insulin dose at the first (P < 0.05), second (P < 0.025), and third (P < 0.05) evaluations. 8-Iso-PGF(2 alpha) correlated with insulin dose at the first (P < 0.01) and third (P < 0.0025) evaluations. Systemic measures of oxidative stress correlate with insulin requirements in early type 1 diabetes. These results suggest that oxidative stress is taking place in the pancreas and damaging the beta-cell.