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

Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications
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DOI:
10.1016/s0891-5849(03)00185-0
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发表时间:
2003-06-15
影响因子:
7.4
通讯作者:
Domínguez, C
Domínguez, C
中科院分区:
医学1区
文献类型:
--
作者:
Martín-Gallán, P;Carrascosa, A;Domínguez, C

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该研究的目的是确定氧化应激在年轻I型糖尿病患者疾病相关病理生理并发症发病中的潜在作用。检测了26例最近诊断为微血管病变(< 6个月)的年轻糖尿病患者(+DC)、28例无并发症的糖尿病患者(-DC)和40例年龄匹配的健康对照者(CR)的血液样本中脂质过氧化、蛋白质氧化和抗氧化防御系统状态变化的指示性参数。两个糖尿病组的果糖胺和糖化血红蛋白(HbA 1c)值相似。结果表明,红细胞谷胱甘肽过氧化物酶活性,谷胱甘肽含量,血浆β-胡萝卜素显着降低糖尿病患者与对照组相比,但与DC和+DC组之间没有显着差异。抗氧化酶超氧化物歧化酶活性显着较高的糖尿病患者的红细胞独立的微血管并发症的存在。然而,与-DC组相比,+DC组的血浆α-生育酚/总脂质比率显著降低(p = .008)。血浆脂质过氧化指标包括丙二醛、脂质过氧化氢和脂质过氧化物,无论是否存在并发症,糖尿病患者的脂质过氧化指标均显著升高。通过对血浆蛋白羰基水平的定量,显示了蛋白质氧化损伤的证据,(0.61 +/- 0.09 mmol/mg prot),在+DC患者中更高(0.75 +/- 0.09 mmol/mg蛋白质)与对照组(0.32 +/- 0.03 mmol/mg蛋白质; p <0.01)的比较以及蛋白质结合羰基的免疫印迹分析。此外,通过评估晚期氧化蛋白产物(AOPP)(被认为是氧化白蛋白指标),在+DC患者中观察到蛋白氧化显著增加;+DC患者的AOPP值显著高于-DC患者(p < .01)和CR患者(p < .0001)。这些结果表明,氧化修饰的蛋白质作为一个差异因素可能与糖尿病并发症的发病机制。(C)2003年爱思唯尔公司
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.