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Oxidative Stress and Insulin Requirements in Patients with Recent-Onset Type 1 Diabetes

Departments of Medicine (R.D.H., K.D.B., D.R.M., S.S.W.), Biochemistry and Molecular Pharmacology (K.V.D.), and Community Medicine and Statistics (G.H.), West Virginia University, Morgantown, West Virginia 26506-9159

Address all correspondence and requests for reprints to: Robert D. Hoeldtke, M.D., Ph.D., Department of Medicine, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center, P.O. Box 9159, Morgantown, West Virginia 26506-9159. E-mail: rhoeldtke{at}hsc.wvu.edu.

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 F₂ (8-iso-PGF₂). 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-PGF₂ 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-PGF₂ 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 ß-cell.

This work was supported by NIH Grant DK-32239 (to R.D.H.) and the Compton Nutrition Foundation.

Abbreviations: DCCT, Diabetes Control and Complications Trial; HgbA₁, hemoglobin A₁; iNOS, inducible nitric oxide synthase; NOx, nitrite and nitrate; NTY, nitrotyrosine; 8-iso-PGF₂, 8-iso-prostaglandin F₂.

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