胰岛素泵对2型糖尿病慢性肾脏疾病患者不同时期体内氧化应激水平影响的观察

Effect of insulin pump on oxidative stress in T2DM patients with CKD in different courses

目的探讨短期胰岛素泵强化治疗对糖尿病慢性肾脏疾病(CKD)患者不同时期体内氧化应激水平的影响。方法选取T2DM患者80例为T2DM组,再根据白蛋白尿/肌酐比值(UACR)分为正常白蛋白尿(NA)亚组,微量白蛋白尿(MA)亚组,临床肾病(CA)亚组。另选同期健康体检者30名为正常对照(NC)组,应用胰岛素泵对T2DM组强化治疗2周,比较治疗前后氧化应激指标8-羟基脱氧鸟苷(8-OHdG)、3-硝基酪氨酸(3-NT)、谷胱甘肽(GSH)及超氧化物歧化酶(SOD)的变化情况。结果 (1)治疗前T2DM组8-OHdG、3-NT、HbA1c、BUN、Cr水平及胰岛素抵抗指数(HOMA-IR)高于NC组,且随着UACR增加而增加,组间差异有统计学意义(P<0.05);T2DM组GSH、SOD水平低于NC组(P<0.05),且随着UACR增加而降低,但NA、MA、CA组间GSH、SOD比较差异无统计学意义(P>0.05)。(2)治疗后T2DM组血压、血糖、TG、TC、LDL-C、HOMA-IR较治疗前均下降;HDL-C升高,差异有统计学意义(P<0.05);但HbA1c治疗前后差异无统计学意义(P>0.05)。(3)治疗后NA、MA、CA组8-OHdG、3-NT水平降低;GSH、SOD水平升高。但NA、MA组变化较CA组显著,差异有统计学意义(P<0.05)。(4)相关分析显示,8-OHdG、3-NT和HbA1c、病程、HOMA-IR及FPG呈正相关,GSH、SOD和HbA1c、病程、HOMA-IR及FPG呈负相关。结论 CKD早期使用胰岛素泵强化治疗可改善患者体内氧化应激水平,延缓或阻止向临床肾病期和终末期肾病进展。

Objective To explore the effect of short-term insulin pump intensive therapy on oxidative stress （OS） in T2DM nephropathy patients in different courses. Methods Eighty T2DM patients were divided, according to urine albumin /creatinine ratio （UACR）, into three groups： normal albuminuria （NA）, micro albuminuria （MA）, clinical albuminuria （CA）, and thirty healthy persons were randomly chosen as normal control （NC） group. After two weeks insulin pump intensive therapy, the levels of oxidative stress indexes 8-hydroxy deoxyguanosine （8-OhdG）, 3-nitrotyrosine （3-NT）, glutathione （GSH）, and superoxide dismutase （SOD） of the T2DM group were detected and compared. Results （1）. Before the insulin pump intensive therapy, in the T2DM group the levels of 8-OhdG, 3- NT, HbA1c, BUN, Cr level, and IR index （HOME-IR） were higher than those in the NC group, and they were increasing with the UACR increasing, and there was significant difference shown among all the groups （P〈0.05）; the levels of GSH and SOD in the T2DM group were lower than those in the NC group （P〈0.05）,and they were decreasing with the UACR increasing, and there was no significant difference shown among the NA, MA, and CA groups （P〉0.05）. （2）. After the insulin pump intensive therapy, the blood pressure, blood glucose, TG, TC, LDL-C, and HOME-IR were significantly lowered than before treatment, and HDL-C increased （P〈0.05）, however, the level of HbA1c was not statistically different in the T2DM group （P〉0.05）. （3）. After the insulin pump intensive therapy, the 8-OhdG and 3-NT levels reduced, GSH and SOD levels raised in the NA, MA, and CA groups, whilst the changes in the NA and MA groups were more significant than in the CA group （P〈0.05）. （4）. Correlation analysis showed that： the 8-OhdG and 3-NT levels were correlated positively with HbA1c, course of disease, HOME-IR, and FPG, but the GSH and SOD levels were negatively correlated with HbA1c, course of disease, HOME-IR, and FPG. Conclusion In the early stage of DN, using insulin pump intensive therapy can markedly improve the oxidative stress level inside the patients, and can slow down or stop the progress to the clinical albuminuria period and end-stage of renal disease.