Oxidative stress is defined as an imbalance between prooxidants and antioxidants in favor of the former (1), and diabetic patients are considered a risk group for increased oxidative stress (2,3). Studies regarding oxidant/antioxidant balance in type 1 diabetic children and adolescents have given conflicting results (4–7). The aim of this study was to determine whether serum hydroperoxides (reactive oxygen metabolites [ROMs]) as oxidative markers and plasma α-tocopherol (vitamin E) and coenzyme Q10 as indexes of antioxidant capacity could be related to metabolic control in 75 unselected children, adolescents, and young adults with type 1 diabetes. ROMs are the first markers of oxidation and one of the most reliable indicators of oxidative stress. Vitamin E is an important chain-breaking antioxidant factor controlling LDL oxidation. Coenzyme Q10 is an electron carrier-proton translocator in the respiratory chain and is an antioxidant factor by directly scavenging radicals or indirectly by regenerating vitamin E. ROMs were assayed using the kit d-ROMs test (Diacron), which is based on the Fenton reaction (8). Vitamin E was determined by reversed-phase high-performance liquid chromatography. Coenzyme Q10 was also determined by reversed-phase high-performance liquid chromatography, according to the method of Grossi et al. (9). Statistical significance was assessed using Student’s t test and Pearson correlation index for normally distributed data and using Mann-Whitney and Spearman rank correlation for nonnormally distributed data. All results that were nominally significant at P < 0.05 are indicated. Diabetic patients did not have different ROMs, vitamin E, and coenzyme Q10 levels from age-matched control subjects. Significant positive correlations were found between the following parameters: vitamin E and coenzyme Q10, coenzyme Q10 and HbA1c, and vitamin E and HbA1c. No correlation was observed between ROM levels and coenzyme Q10, vitamin E, or HbA1c values. Vitamin E and coenzyme Q10 values were higher in patients (n = 37) with poor control (HbA1c >8%) than in those (n = 38) with good control (HbA1c <8%) (vitamin E, 25.2 ± 9.5 vs. 20.9 ± 4.6, P = 0.044; coenzyme Q10, 1.12 ± 0.56 vs. 0.82 ± 0.33, P = 0.012, respectively). The patients with retinal or renal complications (n = 19) compared with those without had higher values of vitamin E (25.8 ± 7.1 vs. 20.9 ± 4.8, P = 0.009).
Therefore, in our patients vitamin E levels increased in all of the situations where an increase of oxidative stress was putative, i.e., in the presence of poor metabolic control and complications. This result is in disagreement with most of the data of the literature (5,7,10,11), but in agreement with a few studies (12,13). However, a further confirmation of this result is indirectly provided by our findings regarding coenzyme Q10. In fact, coenzyme Q10 levels, like vitamin E levels, are also higher in poorly controlled than in well-controlled patients and are positively correlated with HbA1c values. This finding is not surprising because these two antioxidants have strict physiological interrelationships and are positively intercorrelated in both the patients and control subjects. On the other hand, it has already been demonstrated that high-glucose conditions produce an overexpression of intracellular antioxidant enzymes in human endothelial cells in culture (14) or in skin fibroblasts from diabetic patients (15) and that the decreased susceptibility to oxidative stress in diabetic rats is associated with an increase in mitochondrial glutathione and coenzyme Q contents (16). This effect seems to represent an adaptive response to increased oxidative stress. In very young patients, this response is high enough to neutralize the increase in reactive oxygen species. In fact, we found this unchanged in the blood of our patients.
