Hypouricemia linked to an overproduction of nitric oxide is an early marker of oxidative stress in female subjects with type 1 diabetes

OBJECTIVE: The aim of this study is to verify whether, early in the course of type 1 diabetes and assuming hyperglycemia as the only risk factor, women demonstrate a change in oxidative status due to an interaction between nitric oxide (NO) and uric acid production. METHODS: Thirty-eight women with type 1 diabetes of less than 10 years' duration and with no diabetic complications were compared with 25 matched healthy female controls. Insulin, C-peptide, NO, HbA(1c) and oxidative stress metabolites were determined from venous blood samples taken from all patients after a 12 h overnight fast. Urine samples were used for urinary uric acid determination. RESULTS: Most oxidative stress metabolites were significantly increased (p < 0.0001), while plasmatic and urinary uric acid levels were significantly lower (p < 0.0001) in patients with type 1 diabetes compared with controls. Mean NO levels were inversely related to uricemia. Bivariate regression analysis showed a significant correlation between plasmatic uric acid and NO (p = 0.004), ascorbic acid (p = 0.042), triglycerides (p = 0.014) and HbA(1c) (p < 0.0001). Linear multivariate regression analysis showed a significant relationship between HbA(1c) and plasmatic uric acid (beta = - 0.465, p = 0.0004). CONCLUSIONS: Oxidative stress is already present in the early stages of type 1 diabetes. We conclude that the initial increase in oxidative stress could be linked to a reduction in plasmatic levels of uric acid, which is probably directly caused by an overproduction of NO.