2020 年第 11 期 第 15 卷

利拉鲁肽与二甲双胍对超重2型糖尿病患者肠道菌群的影响

Effect of liraglutide and metformin on the intestinal flora in overweight patients with type 2 diabetes

作者：邢英1闫军2郑嵘炅3李雅丽4木胡牙提5

英文作者：Xing Ying1， Yan Jun2， Zheng Rongjiong3， Li Yali4， Muhuyati5

单位：1新疆医科大学第一附属医院内分泌科，乌鲁木齐830000；2新疆医科大学第二附属医院普外科，乌鲁木齐830000；3新疆医科大学第一附属医院感染性疾病科，乌鲁木齐830000；4新疆医科大学第一附属医院综合内四科，乌鲁木齐830000；5新疆医科大学第一附属医院综合心脏内科，乌鲁木齐830000

英文单位：1Department of Endocrinology the First Affiliated Hospital of Xinjiang Medical University Urumqi 830000 China; 2Department of General Surgery the Second Affiliated Hospital of Xinjiang Medical University Urumqi 830000 China; 3Department of Infectious Diseases the First Affiliated Hospital of Xinjiang Medical University Urumqi 830000 China; 4the 4th Department of General Internal Medicine the First Affiliated Hospital of Xinjiang Medical University Urumqi 830000 China; 5Department of General Cardiology the First Affiliated Hospital of Xinjiang Medical University Urumqi 830000 China

关键词：2型糖尿病；二甲双胍；利拉鲁肽；肠道菌群

英文关键词：Type2diabetes;Metformin;Liraglutide;Intestinalflora 

• 摘要：

• 目的 探究利拉鲁肽与二甲双胍对超重2型糖尿病患者肠道菌群的影响。方法 选取2016年7月至2019年3月新疆医科大学第一附属医院收治的超重2型糖尿病患者81例，应用随机数字表法分为观察组(41例)和对照组（40例），对照组给予基础治疗联合二甲双胍治疗，观察组在对照组治疗基础上联合利拉鲁肽治疗；比较2组患者治疗前和治疗6、12周后体重指数、空腹血糖、糖化血红蛋白、血脂、肠道菌群和血清丙磺舒特异性阻断泛连接蛋白1（pannexin-1）、脂肪酸结合蛋白4（FABP4）水平，以及治疗期间不良反应发生率和3个月随访期间主要不良心血管事件发生率。结果 治疗6、12周后2组体重指数、空腹血糖、糖化血红蛋白、三酰甘油、低密度脂蛋白胆固醇水平均低于治疗前，且观察组均低于对照组，高密度脂蛋白胆固醇水平均高于治疗前，且观察组高于对照组（均P<0.05）。治疗6、12周后2组肠道菌群拟杆菌、乳酸杆菌、双歧杆菌水平均高于治疗前，且观察组均高于对照组［治疗6周后：(8.9±0.8)LogN/g湿便比（8.5±0.7）LogN/g湿便、（6.0±0.7）LogN/g湿便比（5.6±0.7）LogN/g湿便、（7.9±0.8）LogN/g湿便比（7.6±0.8）LogN/g湿便；治疗12周后：(9.6±0.9)LogN/g湿便比（9.0±1.0）LogN/g湿便、（6.6±1.2）LogN/g湿便比（6.0±1.3）LogN/g湿便、（8.6±1.1）LogN/g湿便比（8.0±1.1）LogN/g湿便］，而酵母菌和血清pannexin-1、FABP4水平均低于治疗前，且观察组均低于对照组（均P＜0.05）。观察组总不良反应发生率、主要不良心血管事件发生率与对照组比较，差异均无统计学意义（均P＞0.05）。结论 利拉鲁肽与二甲双胍联合治疗超重2型糖尿病患者，有助于降低血清pannexin-1、FABP4水平，控制血糖，调节血脂，减轻体质量，改善肠道菌群失调，且安全性较好。

• Objective To investigate the effect of liraglutide and metformin on the intestinal flora in overweight patients with type 2 diabetes (T2DM). Methods Totally 81 cases of overweight T2DM patients admitted to the First Affiliated Hospital of Xinjiang Medical University from July 2016 to March 2019 were selected. They were divided into observation group (41 cases) and control group (40 cases) by random number table method. The control group was treated with basic treatment combined with metformin; the observation group was treated with liraglutide on the basis of the control group. The body mass index, fasting blood glucose, glycated hemoglobin and blood lipid, intestinal flora, and serum probenecid-specific blocker pannexin-1 (pannexin-1), fatty acid binding protein 4 (FABP4) levels were compared between the two groups before and after 6, 12 weeks after treatment. The incidence of adverse reactions during treatment and the incidence of major adverse cardiovascular events (MACE) during the 3-month follow-up period were compared between the two groups. Results After 6 and 12 weeks of treatment, the levels of body mass index, fasting blood glucose, glycated hemoglobin, triglyceride, and low-density lipoprotein cholesterol were lower than before treatment; the indexes were lower in the observation group than those in control group; the high density lipoprotein cholesterol level was higher than before treatment; it was higher in observation group than in control group（all P<0.05）. After 6 and 12 weeks of treatment, the levels of bacteroides, lactobacillus and bifidobacterium of the intestinal flora in both groups were higher than before treatment; they were higher in the observation group than in control group ［after 6 weeks of treatment: (8.9±0.8)LogN/g wet stool vs (8.5±0.7) LogN/g wet stool, (6.0±0.7)LogN/g wet stool vs (5.6±0.7)LogN/g wet stool, (7.9±0.8)LogN/g wet stool vs (7.6±0.8)LogN/g wet stool; after 12 weeks of treatment: (9.6±0.9)LogN/g wet stool vs (9.0±1.0)LogN/g wet stool, (6.6±1.2)LogN/g wet stool vs (6.0±1.3)LogN/g wet stool, (8.6±1.1)LogN/g wet stool vs (8.0±1.1)LogN/g wet stool］;the levels of yeast, serum pannexin-1 and FABP4 were lower than those before treatment (all P<0.05). Compared with the control group, the total incidence of adverse reactions and the incidence of MACE in observation group were not statistically significant (all P>0.05). ConclusionLiraglutide and metformin in overweight T2DM patients can reduce serum pannexin-1 and FABP4 levels, control blood glucose, regulate blood lipids, reduce weight and improve intestinal flora imbalance.