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 F2α (8-iso-PGF2α). Plasma NOx was 34.0 ± 4.9 μmol/liter in the control subjects and 52.4 ± 5.1, 50.0 ± 5.1, and 49.0 ± 5.2 μmol/liter in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine was 13.3 ± 2.0 μmol/liter in controls and 26.8 ± 4.4, 26.1 ± 4.3, and 32.7 ± 4.3 μmol/liter in the diabetic patients (P < 0.01). 8-Iso-PGF2α 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-PGF2α 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 β-cell.