Liu Xinle, Gan Wei, Zou Yuangao, Yang Bin, Su Zhenzhen, Deng Jin, Wang Lanlan, Cai Jianping
Department of Lab Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Department of Lab Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China.
Oxid Med Cell Longev. 2016;2016:4323198. doi: 10.1155/2016/4323198. Epub 2015 Dec 7.
The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.
2型糖尿病进展的潜在机制复杂多样。近期研究表明氧化应激提供了一个新视角。为了进一步评估2型糖尿病患者核酸氧化与并发症之间的关系,并探索其可能的分子机制,我们研究了1316名受试者,包括633例2型糖尿病患者和683名年龄及性别匹配的健康对照者。通过超高效液相色谱和质谱联用技术(UPLC-MS/MS)测定尿中DNA氧化标志物8-氧代-7,8-二氢-2'-脱氧鸟苷(8-oxodGuo)和RNA氧化标志物8-氧代-7,8-二氢鸟苷(8-oxoGuo)的水平。同时还测定了血清葡萄糖、糖化血红蛋白(HbA1c)、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯(TG)。结果显示,与年龄匹配的健康对照者相比,有/无并发症的糖尿病患者尿中8-oxodGuo和8-oxoGuo水平均显著升高(分别为p = 0.02和p < 0.001)。有并发症的患者,尤其是大血管并发症患者,其8-oxoGuo水平高于无并发症患者,而血清葡萄糖和脂质浓度无差异。这一发现表明DNA和RNA的氧化损伤作为一种分子机制在2型糖尿病进展中起作用。8-oxoGuo水平升高可能是2型糖尿病并发症的一个危险因素,尤其是在糖尿病大血管并发症中。