达格列净联合二甲双胍在肥胖/超重型T2DM中的应用及对肠道微生态、adropin、chemerin、irisin的影响

Application of dapagliflozin combined with metformin in obese/overweight T2DM and its effect on intestinal microbiota,adropin,chemerin,and irisin

目的探讨达格列净联合二甲双胍在肥胖/超重型2型糖尿病(type 2 diabetes mellitus,T2DM)中的应用效果及对肠道微生态、能量平衡相关蛋白(adropin)、趋化素(chemerin)、鸢尾素(irisin)的影响。方法按照电脑随机数字表法,按1∶1原则将112例肥胖/超重型T2DM患者分为两组,各56例。对照组给予二甲双胍治疗,观察组给予达格列净联合二甲双胍治疗。比较两组血糖水平[空腹血糖(fasting plasma glucose,FPG)、餐后2 h血糖(postprandial two-hour plasma glucose,2 hPG)、糖化血红蛋白(hemoglobin A1c,HbA1c)]、稳态模型胰岛素抵抗指数(homeostasis model assessment,HOMA-IR)、腰围、体质量指数(body mass index,BMI)、血脂指标[高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、三酰甘油(triglycerides,TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、总胆固醇(total cholesterol,TC)]、肠道微生态、adropin、chemerin、irisin水平及不良反应。结果观察组治疗后3个月、6个月FPG、2 hPG、HbA1c、HOMA-IR低于对照组(P<0.05);观察组治疗6个月后腰围、BMI低于对照组(P<0.05);观察组治疗3、6个月后TG低于对照组,HDL-C高于对照组(P<0.05);观察组治疗6个月后肠球菌、肠杆菌数量低于对照组,拟杆菌、乳酸杆菌数量高于对照组(P<0.05);观察组治疗3、6个月后adropin、irisin高于对照组,chemerin低于对照组(P<0.05)。结论达格列净联合二甲双胍治疗肥胖/超重型T2DM,可有效降低血糖水平,改善胰岛素抵抗、血脂代谢及肠道微生态,缓解肥胖/超重,安全性高,降低chemerin,提高adropin、irisin可能是两者联合发挥抗T2DM效应的一个分子水平机制。

Objective To investigate the application effect of dapagliflozin combined with metformin in obese/overweight type 2 diabetes mellitus(T2DM)and its effect on intestinal microbiota,adropin,chemerin,and irisin.Methods According to the computerized random number table method,112 obese/overweight T2DM patients were divided into two groups in a 1∶1 ratio,with 56 cases in each group.The control group was treated with metformin,and the observation group was treated with dapagliflozin combined with metformin.The blood glucose levels[fasting blood glucose(FPG),2 h postprandial blood glucose(2 hPG),glycosylated hemoglobin A1c(HbA1c)],homeostasis model assessment-insulin resistance(HOMA-IR),waist circumference,body mass index(BMI),blood lipid indexes[high density lipoprotein(HDL-C),triacylglycerol(TG),low density lipoprotein(LDL-C),total cholesterol(TC)],intestinal microbiota,serum adropin,chemerin,irisin and adverse reactions were compared between the two groups.Results The FPG,2 hPG,HbA1c and HOMA-IR of the observation group were lower than those of the control group at 3 months and 6 months after treatment(P<0.05).The waist circumference and BMI of the observation group were lower than those of the control group at 6 months after treatment(P<0.05).At 3 and 6 months after treatment,TG was lower in the observation group than in the control group,and HDL-C was higher than that of the control group(P<0.05).The number of Enterococcus and Enterobacter in the observation group at 6 months after treatment was lower than that of the control group,while the number of Bacteroides and Lactobacillus was higher than that of the control group(P<0.05).In the observation group,adropin and irisin were higher than those in the control group at 3 and 6 months after treatment,while chemerin was lower than that in the control group(P<0.05).Conclusion Dapagliflozin combined with metformin in the treatment of obesity/overweight T2DM can effectively reduce blood glucose levels,improve insulin resistance,blood lipid metabolism and intestinal microecology,relieve obesity/overweight,and have high safety.Decreasing chemerin and increasing adropin and irisin may be a molecular mechanism for the combined anti-T2DM effect of the two.