达格列净对初诊2型糖尿病患者胰岛β细胞功能及肠道菌群的影响  

Effect of dapagliflozin on regulating gut microbiota and improving function of beta-cells in newly diagnosed type 2 diabetes mellitus

作　　者：王绘 张琳琳 高玮 叶小龙[2] 鲁一兵[2] 丁大法[2] Wang Hui;Zhang Linlin;Gao Wei;Ye Xiaolong;Lu Yibing;Ding Dafa(Department of Endocrinology,Yancheng Tinghu District People Hospital,Yancheng 224006,China;Department of Endocrinology,Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China)

机构地区：[1]江苏省盐城市亭湖区人民医院内分泌科,盐城224006 [2]南京医科大学第二附属医院内分泌科,南京210011

出　　处：《中华糖尿病杂志》2022年第4期337-344,共8页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：江苏省重点研发计划(社会发展)项目(BE2016800);江苏省卫生健康委科研项目(M2021056)。

摘　　要：目的探讨达格列净对新诊断2型糖尿病(T2DM)患者肠道菌群及胰岛β细胞功能的影响。方法本研究为随机对照试验。选取2018年12月至2019年9月在江苏省盐城市亭湖区人民医院住院的52例新诊断T2DM患者作为研究对象,同时选取体检中心20名健康体检者作为正常对照组。T2DM患者住院后在专科护士的指导、糖尿病饮食的基础上予胰岛素强化治疗,血糖达标1周后停用胰岛素,采用随机数字表法分为达格列净组(剂量为10 mg,1次/d)和二甲双胍组(剂量为0.5~1.0 g,2次/d)。两组均用药12周。收集两组患者治疗前及治疗后的一般资料并检测临床指标,包括体重指数(BMI)、腰围、血尿酸、糖化血红蛋白(HbA_(1c))、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(2hPG)、稳态模型评估胰岛素抵抗指数(HOMA-IR)、稳态模型评估β细胞功能指数(HOMA-β)等指标。同时收集两组患者治疗前及治疗后的粪便标本,通过16SrDNA测序检测粪便的菌群组成。组内各指标的比较采用配对样本t检验,组间各指标的比较采用单因素方差分析或Kruskal-Wallis秩和检验。采用Spearman相关分析法分析肠道菌群与T2DM临床相关指标的相关性。结果达格列净组26例,二甲双胍组26例。与二甲双胍组治疗后比较,达格列净组治疗后BMI、腰围、血尿酸、LDL-C、HOMA-IR水平下降,HDL-C、HOMA-β水平升高,差异均具有统计学意义(P<0.05)。二甲双胍组、达格列净组和正常对照组分别有13、11和20例最终成功收集了粪便标本。二甲双胍组和达格列净组患者治疗后肠道菌群多样性显著增加(均P<0.05),与二甲双胍组治疗后比较,达格列净组治疗后肠杆菌属、普氏梭杆菌属丰度水平明显降低,而普拉梭菌属和普雷沃菌属丰度明显升高,差异均具有统计学意义(P<0.05)。Spearman相关分析结果显示,布劳特菌属、丹�Objective To study the effect of dapagliflozin on the composition of the gut microbiota and the function ofβ-cells in newly diagnosed type 2 diabetes mellitus(T2DM).Methods A total of 52 newly diagnosed T2DM patients who were hospitalized in Yancheng Tinghu District People Hospital from December 2018 to September 2019 were enrolled,and 20 healthy people from the physical examination center were selected as the control group.In hospital,patients with T2DM were given intensive insulin therapy based on the guidance of specialist nurses and diabetic diet,which stopped insulin therapy one week after the blood glucose reached the target.T2DM patients were divided into two groups according to a random number table method:dapagliflozin group(dose of 10 mg,once per day)and metformin group(dose of 0.5 to 1.0 g,twice per day).The two groups were both treated for 12 weeks.The general data of the two groups of patients were collected and various indexes before and 12 weeks after treatment were recorded,including body mass index(BMI),waist circumference,uric acid,glycated hemoglobin A1c(HbA_(1c)),triglycerides(TG),high-density lipoprotein-cholesterol(HDL-C),low-density lipoprotein-cholesterol(LDL-C),fasting blood glucose(FPG),2 h postprandial blood glucose(2hPG),homeostasis model assessment of insulin resistance(HOMA-IR)and beta-cell function(HOMA-β),and so on.The feces samples of the two groups of the patients in both groups were collected before intervention and at 12 weeks after intervention.16SrDNA sequencing to detect changes in gut microbiota composition were evaluated.The t test was used for the comparison between the two groups.The comparison of each index between groups using an analysis of one-way analysis of variances or Kruskal-Wallis test.Spearman correlation analysis was used to analyze the correlation between differential gut microbiota and clinical parameters of T2DM.Results There were 26 cases in dapagliflozin group,26 cases in metformin group.Compared to metformin group after 12 weeks treatment,the BMI,LDL-

关 键 词：糖尿病 2型 达格列净 肠道菌群 胰岛Β细胞功能 

分 类 号：R587.1[医药卫生—内分泌]