非诺贝特联合热量限制饮食治疗非酒精性脂肪性肝病合并2型糖尿病患者疗效研究

Therapeutic efficacy of fenofibrate at base of calorie restriction diet in the treatment of patients with non-alcoholic fatty liver disease and type 2 diabetes

目的探讨应用非诺贝特联合热量限制饮食治疗非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者的疗效及患者血清人类软骨糖蛋白-39(HCGP39)、脂联素(APN)和非对称二甲基精氨酸(ADMA)水平的变化。方法将128例NAFLD合并T2DM患者随机分为对照组64例和观察组64例,分别采用热量限制饮食或在此基础上给予非诺贝特口服治疗、观察12周。采用免疫层析法检测血清糖化血红蛋白(HbA1c)水平,采用葡萄糖氧化酶法检测血清空腹血糖(FPG)和餐后2h血糖(2 h PPG)水平,采用磁微粒化学发光法检测血清空腹胰岛素(FINS)水平,并计算胰岛素抵抗(IR)指数。采用ELISA法检测血清HCGP39、APN和ADMA水平。结果在治疗结束时,观察组血清谷丙转氨酶(ALT)水平为(39.4±5.3)U/L,显著低于对照组【(46.8±7.9)U/L,P<0.05】,血清谷草转氨酶(AST)水平为(46.3±4.4)U/L,显著低于对照组【(54.7±7.5)U/L,P<0.05】,血清谷氨酰转移酶(GGT)水平为(33.9±8.6)U/L,显著低于对照组【(43.7±14.6)U/L,P<0.05】;血清FBG水平为(5.9±1.9)mmol/L,显著低于对照组【(6.8±2.0)mmol/L,P<0.05】,血清2 h PPG水平为(7.4±2.2)mmol/L,显著低于对照组【(8.5±2.4)mmol/L,P<0.05】,IR水平为(4.1±0.4),显著低于对照组【(4.7±0.5),P<0.05】;血清总胆固醇(TC)水平为(1.5±0.2)mmol/L,显著低于对照组【(2.1±0.2)mmol/L,P<0.05】,血清三酰甘油(TG)水平为(4.0±0.7)mmol/L,显著低于对照组【(5.5±0.8)mmol/L,P<0.05】,血清低密度脂蛋白(LDL)水平为(2.1±0.5)mmol/L,显著低于对照组【(2.5±0.6)mmol/L,P<0.05】,而血清高密度脂蛋白(HDL)水平为(1.6±0.5)mmol/L,显著高于对照组【(1.4±0.3)mmol/L,P<0.05】;血清HCGP39水平为(61.4±7.5)ng/mL,显著低于对照组【(73.3±9.2)ng/mL,P<0.05】,血清ADMA水平为(1.8±0.3)μmol/mL,显著低于对照组【(2.2±0.5)μmol/mL,P<0.05】,而血清APN水平为(14.6±6.2)ng/mL,显著高于对照组【(11.3±4.9)ng/mL,P<0.05】。结论应用非诺贝特联合热量限制饮食可降低NAFLD合并T2DM患者血清HCGP39和ADMA水平,而提高血清APN水平,可能与改善了IR,进而改善了肝功能和糖脂代谢有关。

Objective The aim of this study was to investigate the efficacy of fenofibrate at base of calorie restriction diet in treatment of patients with non-alcoholic fatty liver disease(NAFLD)and type 2 diabetes mellitus(T2DM)and serum human cartilage glycoprotein-39(HCGP39),adiponectin(APN)and asymmetric dimethylarginine(ADMA)level changes.Methods 128 patients with NAFLD complicated by T2DM were randomly divided into control(n=64)and observation group(n=64),receiving calorie-restricted diet or oral fenofibrate at the basis of calorie-restricted diet,respectively for 12 weeks.Serum glycated hemoglobin(HbA1c)levels were detected by immunochromatography,serum fasting blood glucose(FPG)and postprandial 2 hour blood glucose(2 h PPG)level were detected by glucose oxidase method,serum fasting insulin(FINS)level was detected by microparticle chemiluminescence method,by which the insulin resistance(IR)index was calculated,and serum HCGP39,APN and ADMA levels were detected by ELISA.Results At the end of 12 week observation,serum alanine aminotransferase level in the observation group was(39.4±5.3)U/L,significantly lower than[(46.8±7.9)U/L,P<0.05],serum aspartate aminotransferase level was(46.3±4.4)U/L,significantly lower than[(54.7±7.5)U/L,P<0.05],and serum glutamyl transferase level was(40.7±14.6)U/L,significantly lower than[(43.7±14.6)U/L,P<0.05]in the control;serum FBG level was(5.9±1.9)mmol/L,significantly lower than[(6.8±2.0)mmol/L,P<0.05],serum 2 h PPG level was(7.4±2.2)mmol/L,significantly lower than[(8.5±2.4)mmol/L,P<0.05],and IR level was(4.1±0.4),significantly lower than that【(4.7±0.5),P<0.05】in the control;serum total cholesterol level was(1.5±0.2)mmol/L,significantly lower than[(2.1±0.2)mmol/L,P<0.05],serum triacylglycerol level was(4.0±0.7)mmol/L,significantly lower than[(5.5±0.8)mmol/L,P<0.05],serum low-density lipoprotein level was(2.1±0.5)mmol/L,significantly lower than[(2.5±0.6)mmol/L,P<0.05],while serum high density lipoprotein level was(1.6±0.5)mmol/L,significantly higher than[(1.4±0.3)mmol/L,P<0.05]in the control;serum HCGP39 level was(61.4±7.5)ng/mL,significantly lower than[(73.3±9.2)ng/mL,P<0.05],serum ADMA level was(1.8±0.3)μmol/mL,significantly lower than[(2.2±0.5)μmol/mL,P<0.05],while serum APN level was(14.6±6.2)ng/mL,significantly higher than[(11.3±4.9)ng/mL,P<0.05]in the control.Conclusion The administration of fenofibrate at base of calorie restriction diet in treating patients with NAFLD and T2DM could reduce serum HCGP39 and ADMA levels and elevate serum APN levels,which might reduce liver injury,improve insulin resistance,and thus improve liver function,and glucose and lipid metabolism.