胰岛素抵抗患者外周血白细胞端粒长度检测

Leukocyte telomere shortening occurs in insulin resistance

目的:检测胰岛素抵抗型及2型糖尿病者外周白细胞中端粒长度,并通过分析其与年龄、病程、胰岛素抵抗程度、及炎症水平的相关性,探讨端粒长度减短作为2型糖尿病发病风险指标的可能性。方法:共选取113例研究对象。41例无胰岛素抵抗血糖正常者为对照,40例具胰岛素抵抗特征但血糖正常者为胰岛素抵抗组(insulin resistance,IR),32例具胰岛素抵抗特征的糖尿病患者为2型糖尿病组(type 2 diabetes,T2D)。高压液相色谱法检测HbA_1 c,电化学发光法检测高敏C反应蛋白(high sensitity C reactive protein,hs-CRP),测量体重指数(body mass index,BMI)、腰臀比(wrist-hip ratio,WHR),提取研究对象外周白细胞,定量PCR检测端粒长度比值(T/S比值)来评估端粒长度。结果:3组研究对象年龄、性别、BMI、WHR具可比性。胰岛素抵抗指数,IR(6.1±1.8)及T2D组(7.8±1.2)均显著高于CTL组(2.0±1.0),但组间无差异。端粒长度,IR(2.2±0.6)及T2D组(2.0±0.5)较CTL组(3.9±0.6)明显减短,T2D组减短更为显著。以端粒长度为因变量,多元线性回归分析显示,HOMA-IR、hs-CRP及HbA1c与端粒长度显著负相关(β=-0.082,P=0.011;β=-0.469,P<0.001;β=-0.088,P=0.013)。结论:胰岛素抵抗和2型糖尿病患者外周白细胞端粒长度均明显缩短,而2型糖尿病患者端粒长度减短更为明显。胰岛素抵抗时端粒长度进一步减短可作为2型糖尿病发病风险的指标。

OBJECTIVE To determine whether telomere shortening occurs in insulin resistance and the possibility that telomere shortening would characterize type 2 diabetes. METHODS Insulin resistance with eulyglyeemia （n = 40）, type 2 diabetic patients （n = 32）, and age-and sex-matched control non-insulin resistant subjects （n = 41） were selected from the department of outpatient of Tongji Hospital. Leukocyte telomere length ratio（T/S ratio） was measured using a quantitative PCR method and ayalyzed. HbAlc and hs-CRP were measured. Peripheral insulin resistance （homeostasis model assessment）, WHR and BMI were carculated. RESULTS HOMAqR was not significantly different between IR and T2D groups, but much significantly higher than in CTL. Mean （SE） TRF lengths of the insulin resistant type 2 diabetic patients （2. 0 ± 0. 5） and IR subjects （2. 2 ± 0. 6） were significantly shorter than those of control subjects （3. 9 ± 0. 6）. Among the biochemical parameters, only levels of HOMA-IR,hs-CRP and HbAlc were negative correlation with shorten telomeres in all subjeets（β=-0. 082, P = 0. 001;β = - 0. 469, P%0. 001 ;β = - 0. 088, P = 0. 013）. CONCLUSION Telomere shortening occurs from insulin resistance to type 2 dia- betes, which decreased with the increased of insulin resistance, hsCRP and HbAlc. This data suggests that telomere shorten- ing in status of insulin resistance would characterize type 2 diabetes,