利拉鲁肽治疗非酒精性脂肪性肝病合并2型糖尿病患者血脂、血管内皮功能和肝纤维化指标的变化*

目的 探讨应用利拉鲁肽治疗非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者血脂、血管内皮功能和血清肝纤维化指标的变化。方法 2014年1月～2018年12月我院收治的NAFLD合并T2DM患者90例,被随机分为对照组45例和观察组45例,分别给予二甲双胍或二甲双胍联合利拉鲁肽治疗12周。检测空腹血糖(FPG)、餐后 2 h 血糖(2hPPG)和糖化血红蛋白(HbA1c),使用高分辨超声诊断仪检测肱动脉内径变化,记录血管舒张内径达到最大值所需的时间(T₁)和舌下含化硝酸甘油后血管达最大内径所需的时间(T₂),计算肱动脉血流介导的内皮依赖性血管舒张功能(EDR)和硝酸甘油介导的内皮非依赖性血管舒张功能(END)。采用放射免疫分析法检测血清透明质酸(HA)、 层粘连蛋白(LN)、 IV型胶原(CIV)和 III型前胶原(PIIIP)。结果 在治疗结束时,观察组和对照组FPG分别为(7.3±1.9)mmol/L对(8.6±1.8)mmol/L,2hPPG分别为(9.8±2.3)mmol/L对(11.4±2.2)mmol/L,HbA1c水平分别为(7.2±1.0)%对(8.3±1.2)%,差异显著(P＜0.05);血清TC分别为(4.8±0.9)mmol/L对(5.6±1.2)mmol/L、TG分别为(1.5±0.4)mmol/L对(2.0±0.6)mmol/L、LDL-C分别为(2.0±0.6)mmol/L对(2.9±0.7)mmol/L和HDL-C分别为(1.6±0.3)mmol/L对(1.3±0.2)mmol/L,差异显著(P＜0.05);T₁分别为(56.1±6.5)s对(62.9±5.8)s,EDR分别为(7.8±1.0)%对(5.2±0.8)%和END分别为(21.3±2.9)%对(17.2±2.5)%,差异显著(P＜0.05);血清HA分别为(70.3±9.2)ng/ml对(85.9±10.3)ng/ml, CIV分别为(50.2±0.7)ng/ml对(67.3±0.9)ng/ml和PIIIP分别为(6.2±0.6)ng/ml对(8.3±0.5)ng/ml,差异显著(P＜0.05)。结论 应用利拉鲁肽治疗NAFLD合并2 型糖尿病患者能有效降低血糖,改善血管内皮功能,纠正脂代谢紊乱,对预防糖尿病患者大血管并发症可能有益。

Efficacy of liraglutide in treatment of patients with nonalcoholic fatty liver disease complicated by type 2 diabetes mellitus

Objective Objective The aim of this study was to investigate the efficacy of liraglutide in treatment of patients with nonalcoholic fatty liver disease( NAFLD) complicated by type 2 diabetes mellitus( T2DM). Methods 90 patients with NAFLD and T2DM were recruited in our hospital between January 2014 and December 2018,and were randomly divided into control( n= 45) and observation group( n= 45). They were treated with metformin or metformin and liraglutide combination for 12 weeks.Fasting blood glucose( FPG),postprandial 2 h blood glucose( 2 h PPG) and glycosylated hemoglobin( HbA1c),blood lipid index and serum hyaluronic acid( HA),laminin( LN),type Ⅳ collagen( CIV),and type Ⅲ procollagen( PIIIP) were assayed. The parameters of brachial artery,such as T1 and T2,endothelium-dependent relaxation( EDR) and endothelium-non-dependent relaxation( END) were recorded by high-resolution ultrasound. Results At the end of three-month treatment,the FPGs in the observation and control group were( 7.3±1.9) mmol/L vs.( 8.6±1.8) mmol/L,and the 2 h PPG were( 9.8±2.3) mmol/L vs.( 11.4±2.2) mmol,and HbA1c were( 7. 2 ± 1. 0) % vs.( 8. 3 ± 1. 2) %,respectively,all significantly different( P < 0. 05);serum TC levels were( 4.8±0.9) mmol/L vs.( 5.6±1.2) mmol/L,TG were( 1.5±0.4) mmol/L vs.( 2.0±0.6) mmol/L,LDL-C were( 2.0±0.6) mmol/L vs.( 2.9±0.7) mmol/L,and HDL-C was( 1.6±0.3) mmol/L vs.( 1.3±0.2) mmol/L,all significantly different( P<0.05);T1 were( 56.1±6.5) s vs.( 62.9±5.8) s,EDR were( 7.8±1.0) % vs.( 5.2± 0. 8) %,and END were( 21. 3 ± 2. 9) % vs.( 17.2±2.5) %,all significantly different( P<0.05);serum HA were( 70.3±9.2) ng/ml vs.( 85.9±10.3) ng/ml,CIV were( 50.2±0.7) ng/ml vs.( 67.3±0.9) ng/ml,and PIIINP were( 6.2±) .0.6) ng/ml vs.( 8.3±0.5) ng/ml,all significantly different( P<0.05) in the two groups. Conclusion Liraglutide is efficacious in treatment of patients with NAFLD and mellitus,which could effectively decrease blood sugar levels,improve vascular endothelial functions and correct lipid metabolism disorder.