Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications

被引:307
作者
Martín-Gallán, P
Carrascosa, A
Gussinyé, M
Domínguez, C
机构
[1] Hosp Materno Infantil Vall Hebron, Ctr Invest Bioquim & Mol, Barcelona 08035, Spain
[2] Hosp Materno Infantil Vall Hebron, Pediat Endocrinol Unit, Barcelona 08035, Spain
关键词
antioxidants; diabetic complications; lipid peroxidation; malondialdehyde; oxidative stress; protein carbonyls; type 1 diabetes mellitus; free radicals;
D O I
10.1016/S0891-5849(03)00185-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aims of the study were to ascertain the potential role of oxidative stress in the onset of disease-related pathophysiological complications in young type I diabetes patients. Indicative parameters of lipoperoxidation, protein oxidation, and changes in antioxidant defense system status were measured in blood samples from 26 young diabetic patients with recently diagnosed (< 6 months) microangiopathy (+DC), 28 diabetic patients without complications (-DC), and 40 healthy age-matched controls (CR). Both diabetic groups presented similar fructosamine and glycated hemoglobin (HbA1c) values. Results showed erythrocyte glutathione peroxidase activity, glutathione content, and plasma beta-carotene to be significantly lower in diabetic patients compared with control subjects, but with no significant differences between -DC and +DC groups. Antioxidant enzyme superoxide dismutase activity was significantly higher in the erythrocytes of diabetic patients independently of the presence of microvascular complications. However, the plasma alpha-tocopherol/total lipids ratio was significantly diminished in +DC group compared with -DC (p = .008). Lipid peroxidation indices measured in plasma included malondialdehyde, lipid hydroperoxides, and lipoperoxides, which were significantly elevated in our diabetic patients regardless of the presence of complications. Evidence of oxidative damage to proteins was shown both through the quantification of plasma protein carbonyl levels, which were significantly higher in -DC (0.61 +/- 0.09 mmol/mg prot), and higher still in the +DC patients (0.75 +/- 0.09 mmol/mg prot) compared with those of controls (0.32 +/- 0.03 mmol/mg prot; p < .01) and immunoblot analysis of protein-bound carbonyls. Additionally, a marked increase in protein oxidation was observed in +DC patients through assessment of advanced oxidation protein products (AOPP) considered to be an oxidized albumin index; AOPP values were significantly higher in +DC than in -DC patients (p < .01) and CR (p < .0001). These results point to oxidatively modified proteins as a differential factor possibly related to the pathogenesis of diabetic complications. (C) 2003 Elsevier Inc.
引用
收藏
页码:1563 / 1574
页数:12
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