·糖尿病临床研究·

　　1型及2型糖尿病患者外周血白细胞端粒长度减短与氧化应激关系的研究

　　杨雁 胡鹏 刘喆隆 严江涛 张晓洁 袁刚

　　[摘要] 目的 分析糖尿病氧化应激对DNA损伤程度与端粒长度的相关性，探讨糖尿病时端粒减短的原因。方法 选取T2DM组62例， T1DM组34例，对照(NC)组41例,提取外周血白细胞，ELISA法检测白细胞中8羟基脱氧鸟苷(8-OHdG)，定量PCR检测端粒长度。结果 T2DM组(2.97±0.85)与T1DM组(1.97±0.87)8-OHdG水平显著高于NC组(0.90±0.44);两组端粒长度比较，T2DM组(1.67±0.50)与T1DM组(1.47±0.50)均较NC组(2.39±0.55)显著减短，且T1DM组端粒长度较T2DM组进一步减短。在3组中，以端粒长度作为因变量进行多元线性回归分析,结果显示，年龄及8-OHdG与端粒长度显著负相关(P=0.048，b=-0.008;P=0.000，b=-0.271)，而FIns水平与端粒长度呈显著正相关(P=0.025，b=0.013);在T2DM组中，年龄及8-OHdG与端粒长度显著负相关(P=0.001，b=-0.018;P=0.023，b=-0.158);在T1DM组中， 8-OHdG与端粒长度显著负相关(P=0.025，b=0.013)。结论 糖尿病患者外周白细胞端粒长度均明显缩短，T1DM患者端粒长度减短更为明显。糖尿病时端粒的减短主要与氧化应激、年龄及胰岛素分泌水平有关。

　　[关键词] 糖尿病, 1型;糖尿病,2型;端粒;氧化性应激

　　Association of shortened telomere length with oxidative stress in leukocytes of T1DM and T2DM patients YANG Yan, HU Peng, YUAN Gang. Department of Endocrinology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

　　Corresponding author: YUAN Gang, E-mail: yangyandoc@yahoo.com.cn

　　【Abstract】Objective To analyze the severity of DNA damage by oxidative stress in diabetic patients and the correlation of diabetic oxidative stress with the changes of telomere length, and to explore the causes of shortened telomere length in diabetic condition. Methods T2DM patients, n=62, T1DM patients, n=34, and non-diabetic subjects, n=41, were enrolled in this trial. The leukocytes of peripheral blood of all subjects were obtained for detecting the 8-hydroxyl deoxyguanosine (8-OHdG) by ELISA. By using a quantitative PCR assay, the telomere length was determined and the average telomere size in leukocyte DNA was measured. Results The 8-OHdG level of T2DM group (2.97±0.85) and T1DM group (1.97±0.87) was significantly higher than that of the control group (0.90±0.44). In comparing the telomere length of T2DM group (1.67±0.50) and T1DM group (1.47±0.50) with the control group (2.39±0.55), that of the former two groups was significantly shortened than that of the later group, and that of the T1DM group was even shorter than that of the T2DM group. In the multivariate linear regression analysis, the telomere length was taken as the dependent variable, and the result showed that in all three groups only the age and 8-OHdG level were negatively correlated with telomere length (P=0.048, b=-0.008; P=0.000, b=-0.271), while the FIns level was positively correlated with telomere length (P=0.025, b=0.013); in the T2DM group, the age and 8-OHdG level were negatively correlated with telomere length (P=0.001, b=-0.018; P=0.023, b=-0.158), but in the T1DM group, the 8-OHdG level was negatively correlated with telomere length (P=0.025, b=0.013). Conclusions The telomere length is significantly shortened in leukocytes of diabetic patients, and the shortening in the telomere of the T1DM patients is more obvious. The telomere shortening in diabetic condition is mainly associated with the oxidative stress induced by hyperglycemia, age, and the level of insulin secretion.

　　【Key words】Diabetes mellitus, type 1, type 2; Telomere; Oxidative stress