Song Fangfang, Jia Wenbo, Yao Ying, Hu Yafei, Lei Lin, Lin Jie, Sun Xiufa, Liu Liegang
Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Clin Sci (Lond). 2007 Jun;112(12):599-606. doi: 10.1042/CS20060323.
Previous studies have postulated the association between oxidative stress and Type 2 diabetes. Considering the long pre-diabetic period with IGR (impaired glucose regulation) and its high risk of developing diabetes, to test this hypothesis, we have investigated oxidative stress pathways and DNA damage in patients with IGR and newly diagnosed Type 2 diabetes. The study population consisted of 92 subjects with NGT (normal glucose tolerance), 78 patients with IGR and 113 patients with newly diagnosed diabetes. Plasma MDA (malondialdehyde) and TAC (total antioxidative capacity) status, erythrocyte GSH content and SOD (superoxide dismutase) activity were determined. A comet assay was employed to evaluate DNA damage. Compared with subjects with NGT, patients with IGR had reduced erythrocyte SOD activity. Patients with diabetes had a higher plasma MDA concentration, but a lower plasma TAC level and erythrocyte SOD activity, than the NGT group. Correlation analysis revealed a strong positive association between IR (insulin resistance) and MDA concentration, but negative correlations with TAC status and SOD activity. With respect to beta-cell function, a positive association with TAC status and an inverse correlation with GSH respectively, were observed. The comet assay revealed slight DNA damage in patients with IGR, which was increased in patients with diabetes. Significant correlations were observed between DNA damage and hyperglycaemia, IR and beta-cell dysfunction. In conclusion, the results of the present study suggest that hyperglycaemia in an IGR state caused the predominance of oxidative stress over antioxidative defence systems, leading to oxidative DNA damage, which possibly contributed to pancreatic beta-cell dysfunction, IR and more pronounced hyperglycaemia. This vicious circle finally induced the deterioration to diabetes.
以往的研究推测氧化应激与2型糖尿病之间存在关联。考虑到糖尿病前期糖耐量受损（IGR）阶段较长且发展为糖尿病的风险较高，为验证这一假设，我们研究了IGR患者及新诊断的2型糖尿病患者的氧化应激途径和DNA损伤情况。研究人群包括92例糖耐量正常（NGT）者、78例IGR患者和113例新诊断的糖尿病患者。测定了血浆丙二醛（MDA）和总抗氧化能力（TAC）水平、红细胞谷胱甘肽（GSH）含量及超氧化物歧化酶（SOD）活性。采用彗星试验评估DNA损伤。与NGT受试者相比，IGR患者红细胞SOD活性降低。糖尿病患者血浆MDA浓度较高，但血浆TAC水平和红细胞SOD活性低于NGT组。相关性分析显示，胰岛素抵抗（IR）与MDA浓度呈强正相关，但与TAC水平和SOD活性呈负相关。关于β细胞功能，分别观察到与TAC水平呈正相关以及与GSH呈负相关。彗星试验显示IGR患者存在轻微DNA损伤，糖尿病患者的损伤增加。观察到DNA损伤与高血糖、IR及β细胞功能障碍之间存在显著相关性。总之，本研究结果表明，IGR状态下的高血糖导致氧化应激超过抗氧化防御系统，引发氧化性DNA损伤，这可能导致胰腺β细胞功能障碍、IR及更明显的高血糖。这种恶性循环最终促使病情恶化为糖尿病。
