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

Association of shortened telomere length with oxidative stress in leukocytes of T1DM and T2DM patients

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患者(T2DM组)62例,T1DM患者(T1DM组)34例,对照(NC)组41名,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 8-OHdG水平T2DM组(2.97±0.85)与T1DM组(1.97±0.87)高于NC组(0.90±0.44);端粒长度T2DM组(1.67±0.50)与T1DM组(1.47±0.50)均较NC组(2.39±0.55)减短,且T1DM组端粒长度较T2DM组进一步减短。在T2DM组中,年龄及8-OHdG与端粒长度呈负相关(P=0.001,β=-0.018;P=0.023,β=-0.158);在T1DM组中,8-OHdG与端粒长度呈负相关(P=0.001,β=-0.358)。结论糖尿病患者外周白细胞端粒长度均缩短,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。

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）, TIDM patients （n= 34）, and non-diabetic subjects （n=41）, were enrolled in this trial. The leukocytes of peripheral blood of all subiects 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. In the multivariate linear regression analysis, the age and 8-OHdG level were negatively correlated with telomere length （P=0. 001,β= -0. 018 ± P=0. 023, β=-0. 158） in T2DM group, but in the T1DM group, only the 8-OHdG level was negatively correlated with telomere length （P=0. 001, β= -0. 358）. Conclusion The telomere length is significantly shortened in leukocytes of diabetic patients, and the shortening in the telomere of the TIDM 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.