利拉鲁肽对2型糖尿病合并非酒精性脂肪性肝病患者糖脂代谢及胰岛素抵抗的影响

Effects of liraglutide on glucose and lipid metabolism and insulin resistance in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease

目的探讨利拉鲁肽对2型糖尿病合并非酒精性脂肪性肝病(non-alcoholic fatty liverdisease,NAFLD)患者糖脂代谢及胰岛素抵抗的影响。方法回顾性分析2018年1月至2020年1月于新疆医科大学第七附属医院就诊的84例2型糖尿病合并NAFLD患者的临床资料,根据用药不同分为观察组(43例)和对照组(41例),对照组患者采用二甲双胍治疗,观察组患者采用二甲双胍联合利拉鲁肽治疗,疗程3个月。检测两组患者治疗前后血糖(空腹血糖、餐后2 h血糖、糖化血红蛋白)、血脂(甘油三酯、总胆固醇、低密度脂蛋白、高密度脂蛋白)、胰岛素抵抗指数、胰岛β-细胞功能指数、脂肪肝严重程度、体重指数(body mass index,BMI)、肝功能[丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartateaminotransferase,AST)],记录患者不良反应。结果(1)治疗后,两组患者空腹血糖[观察组:(5.42±0.63)mmol/L vs(8.87±0.65)mmol/L;对照组:(6.49±0.55)mmol/L vs(8.92±0.71)mmol/L]、餐后2 h血糖[观察组:(8.27±0.95)mmol/L vs(13.84±1.25)mmol/L;对照组:(11.19±1.04)mmol/L vs(13.69±1.18)mmol/L]和糖化血红蛋白[观察组:(5.62±0.64)%vs(7.37±0.87)%;对照组:(6.34±0.71)%vs(7.44±0.75)%]水平均较治疗前显著降低,且观察组显著低于对照组(P均<0.05)。(2)治疗后,两组患者甘油三酯[观察组:(1.80±0.27)mmol/L vs(3.12±0.37)mmol/L;对照组:(2.51±0.32)mmol/L vs(3.05±0.41)mmol/L]、总胆固醇[观察组:(5.31±0.59)mmol/L vs(6.70±0.67)mmol/L;对照组:(5.94±0.65)mmol/L vs(6.64±0.73)mmol/L]和低密度脂蛋白[观察组:(2.42±0.27)mmol/L vs(3.59±0.39)mmol/L;对照组:(2.93±0.31)mmol/L vs(3.65±0.34)mmol/L]水平均显著低于治疗前,高密度脂蛋白水平显著高于治疗前[观察组:(1.63±0.53)mmol/L vs(1.21±0.40)mmol/L;对照组:(1.33±0.41)mmol/L vs(1.16±0.37)mmol/L],差异有统计学意义(P均<0.05)。治疗后,观察组甘油三酯、总胆固醇和低密度脂蛋白水平均显著低于对照组,高密度脂蛋白水平高于对照组,差异有统计学意义(P均<0.05)。(3)治疗后,两组患者胰岛素抵抗指数(观察组:2.59±0.43 vs 5.71±0.59;对照组:3.46±0.51 vs5.58±0.67)和胰岛β-细胞功能指数(152.71±8.84 vs 105.42±8.34;对照组:126.45±9.35vs105.05±8.02)均较治疗前显著改善,与对照组相比,观察组治疗后胰岛素抵抗指数显著降低,胰岛β-细胞功能指数显著升高(P均<0.05)。(4)治疗后,观察组(正常/轻度/中度/重度:12例/19例/9例/1例vs 0例/16例/17例/8例)和对照组(正常/轻度/中度/重度:8例/15例/17例/3例vs 0例/14例/18例/11例)患者脂肪肝严重程度均较治疗前显著改善,且观察组脂肪肝严重程度较对照组轻(z=2.029,P=0.042)。(5)治疗后,两组患者BMI[观察组:(19.97±2.66)kg/m2 vs(24.88±3.28)kg/m2;对照组:(22.11±3.08)kg/m2vs(24.94±3.30)kg/m2]、ALT[观察组:(21.27±5.26)U/L vs(41.02±9.83)U/L;对照组:(33.41±5.02)U/L vs(40.94±9.80)U/L]及AST[观察组:(24.23±3.69)U/L vs(36.33±6.70)U/L;对照组:(30.50±5.04)U/L vs(36.18±6.63)U/L]均显著低于治疗前,且观察组显著低于对照组(P均<0.05)。(6)观察组和对照组不良反应发生率分别为14.63%(6/41)、9.30%(4/43),差异无统计学意义(χ^(2)=0.174,P=0.676)。结论利拉鲁肽可改善2型糖尿病合并NAFLD患者的糖脂代谢和胰岛素抵抗,减轻脂肪肝严重程度,且安全性较好。

Objective To investigate the effects of liraglutide on glucose and lipid metabolism and insulin resistance in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease(NAFLD).Methods The clinical data of 84 patients with type 2 diabetes mellitus complicated with NAFLD in the Seventh Affiliated Hospital of Xinjiang Medical University from January 2018 to January 2020 were retrospectively analyzed.The patients were divided into observation group(43 cases)and control group(41 cases)according to the different treatment.Patients in control group were treated with metformin and patients in observation group were treated with metformin combined with liraglutide for 3 months.Glucose indexes(fasting plasma glucose,2 h postprandial blood glucose,glycosylated hemoglobin),lipid metabolism indexes(triglyceride,total cholesterol,low density lipoprotein,high density lipoprotein),insulin resistance index,isletβcell function index,severity of fatty liver,body mass index(BMI),liver function[alanine aminotransferase(ALT),aspartate aminotransferase(AST)]and adverse reactions were observed before and after treatment.Results(1)After treatment,the fasting blood glucose[observation group:(5.42±0.63)mmol/L vs(8.87±0.65)mmol/L;control group:(6.49±0.55)mmol/L vs(8.92±0.71)mmol/L],2 h postprandial blood glucose[observation group:(8.27±0.95)mmol/L vs(13.84±1.25)mmol/L;control group:(11.19±1.04)mmol/L vs(13.69±1.18)mmol/L]and glycosylated hemoglobin[observation group:(5.62±0.64)%vs(7.37±0.87)%;control group:(6.34±0.71)%vs(7.44±0.75)%]levels of patients in two groups were significantly lower than those before treatment,and the above indexes of patients in observation group were significantly lower than those of control group(all P<0.05).(2)After treatment,the triglyceride[observation group:(1.80±0.27)mmol/L vs(3.12±0.37)mmol/L;control group:(2.51±0.32)mmol/L vs(3.05±0.41)mmol/L],total cholesterol[observation group:(5.31±0.59)mmol/L vs(6.70±0.67)mmol/L;control group:(5.94±0.65)mmol/L vs(6.64±0.73)mmol/L]and low density lipoprotein[observation group:(2.42±0.27)mmol/L vs(3.59±0.39)mmol/L;control group:(2.93±0.31)mmol/L vs(3.65±0.34)mmol/L]levels of patients in two groups were significantly lower than those before treatment,the high density lipoprotein level was significantly higher than that before treatment[observation group:(1.63±0.53)mmol/L vs(1.21±0.40)mmol/L;control group:(1.33±0.41)mmol/L vs(1.16±0.37)mmol/L],the differences were statistically significant(all P<0.05).After treatment,the levels of triglyceride,total cholesterol and low-density lipoprotein of patients in observation group were significantly lower than those of control group,and the level of high-density lipoprotein was higher than that of control group,the differences were statistically significant(all P<0.05).(3)Compared with those before treatment,insulin resistance index(observation group:2.59±0.43 vs 5.71±0.59;control group:3.46±0.51 vs 5.58±0.67)and isletβcell function index(observation group:152.71±8.84 vs 105.42±8.34;control group:126.45±9.35 vs 105.05±8.02)of patients in two groups improved significantly after treatment(all P<0.05).Compared with those in control group,the insulin resistance index of patients in observation group decreased significantly and isletβcell function index increased significantly after treatment(all P<0.05).(4)After treatment,the fatty liver severity of patients in observation group(normal/mild/moderate/severe:12 cases/19 cases/9 cases/1 case vs 0 case/16 cases/17 cases/8 cases)and control group(normal/mild/moderate/severe:8 cases/15 cases/17 cases/3 cases vs 0 case/14 cases/18 cases/11 cases)improved significantly,which was lighter in observation group than that in control group(z=2.029,P=0.042).(5)After treatment,BMI[observation group:(19.97±2.66)kg/m2 vs(24.88±3.28)kg/m2;control group:(22.11±3.08)kg/m2 vs(24.94±3.30)kg/m2],ALT[observation group:(21.27±5.26)U/L vs(41.02±9.83)U/L;control group:(33.41±5.02)U/L vs(40.94±9.80)U/L]and AST[observation group:(24.23±3.69)U/L vs(36.33±6.70)U/L;control group:(30.50±5.04)U/L vs(36.18±6.63)U/L]levels of patients in two groups were significantly lower than those before treatment,and the above indexes of patients in observation group were significantly lower than those of control group(all P<0.05).(6)The incidence of adverse reactions of patients in observation group and control group were 14.63%(6/41)and 9.30%(4/43),respectively,the difference was not statistically significant(χ^(2)=0.174,P=0.676).Conclusions Liraglutide can improve glucose and lipid metabolism,insulin resistance and the severity of fatty liver disease of type 2 diabetes mellitus patients with NAFLD,with good safety.