Martín-Gallán P, Carrascosa A, Gussinyé M, Domínguez C
Biochemistry and Molecular Biology Research Center, Autonomous University, Barcelona, Spain.
J Cell Mol Med. 2007 Nov-Dec;11(6):1352-66. doi: 10.1111/j.1582-4934.2007.00068.x.
Oxidative stress has been implicated as a mechanism underlying hyperglycaemia-associated cellular damage and could play a role in the development of diabetes-related complications. This study aimed to evaluate the significance of changes in oxidant-antioxidant status in 176 child and adolescent diabetic patients at clinical onset, during disease progression and when early microvascular complications appeared. Indicative lipid and protein oxidation markers and antioxidant defence activity were measured in plasma and correlated with clinical data, diabetes duration, long-term glycometabolic control and serum lipids. Compared with their respective age-matched controls, diabetic patients had greater oxidative damage to lipids and proteins, demonstrated through the analysis of hydroperoxides, lipoperoxides and oxidation protein products, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma levels of oxidizable lipids were significantly associated with lipid and protein oxidation products. Overall, plasma antioxidant capacity was significantly and consistently lower from clinical onset onwards. These results suggest that insulin therapy in the first year improved metabolic and oxidant homeostasis and consequently hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation processes, which supports the concept of glucose toxicity and lipotoxicity being interrelated. The greatest increase in lipid and protein oxidative damage biomarkers in young diabetic patients with premature microangiopathy points to oxidative stress as a possible contributing mechanism of microvascular dysfunction. Consequently, tight lipid and glycometabolic control may have therapeutic potential by diminishing oxidative tissue-damaging effects of hyperglycaemia.
氧化应激被认为是高血糖相关细胞损伤的潜在机制，可能在糖尿病相关并发症的发生发展中起作用。本研究旨在评估176例儿童和青少年糖尿病患者在临床发病时、疾病进展过程中以及早期微血管并发症出现时氧化还原状态变化的意义。测定血浆中指示性脂质和蛋白质氧化标志物以及抗氧化防御活性，并将其与临床数据、糖尿病病程、长期糖代谢控制和血脂进行关联分析。与各自年龄匹配的对照组相比，糖尿病患者对脂质和蛋白质的氧化损伤更大，通过对氢过氧化物、脂过氧化物和氧化蛋白质产物的分析得以证实，所有这些指标在发病时均显著升高，在疾病发展的前1.5年下降，此后逐渐上升。可氧化脂质的血浆水平与脂质和蛋白质氧化产物显著相关。总体而言，从临床发病开始，血浆抗氧化能力就显著且持续降低。这些结果表明，第一年的胰岛素治疗改善了代谢和氧化还原稳态，从而减轻了高血糖引起的生物分子氧化损伤。糖尿病相关的高脂血症与脂质和蛋白质氧化过程有关，这支持了葡萄糖毒性和脂毒性相互关联的概念。患有早期微血管病变的年轻糖尿病患者脂质和蛋白质氧化损伤生物标志物的最大增幅表明氧化应激可能是微血管功能障碍的一个促成机制。因此，严格控制脂质和糖代谢可能通过减少高血糖对组织的氧化损伤作用而具有治疗潜力。
