Effect Of Dapagliflozin On Intestinal Flora In Patients With Newly Diagnosed Type 2 Diabetes Mellitus

Objective:The 16 Sr RNA gene sequencing technology was used to analyse the composition of intestinal flora in healthy subjects and newly diagnosed type 2 diabetes mellitus(T2DM)patients before and after treatment with dagliflozin,to investigate the role of intestinal flora in the glucose-lowering mechanism of dagliflozin,and to statistically analyse the effects of dagliflozin on glucolipid metabolism and islet function in newly diagnosed T2 DM patients,so as to lay the foundation for new treatment strategies for patients.Method:In this study,a total of 25 newly diagnosed type 2 diabetes inpatients who met the diagnostic criteria were enrolled between October 2021 and June 2022,taking dagliflozin regularly for 12 weeks,excluding 13 patients who were lost to follow-up during the dosing process.A total of 24 fresh stool samples were finally collected from 12 patients before and after dosing,and stool specimens from 10 healthy people in the physical examination centre were collected as the control group during the same period,using The samples were then sequenced using 16 Sr RNA high-throughput sequencing to analyse the composition of the intestinal flora in each group.Clinical data were also collected from patients before and after drug administration,including age,gender,weight,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FPG),2h postprandial blood glucose(2h PBG),glycated hemoglobin A1c(Hb A1c),fasting insulin(FINS),fasting C-peptide(FCP),Homeostasis model assessment-β(HOMA-β),Homeostasis model assessment of insulin resistance(HOMA-IR),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and statistical analysis of the changes of relevant indexes in the pre-and post-dagliflozin treatment groups.Results:1.After the treatment of dapagliflozin in newly diagnosed patients with T2 DM,the blood glucose level indexes Hb A1 c,FPG,2h PBG were significantly reduced compared with before treatment,and the islets β cell function indexes FCP,FINS,HOMA-IR,HOMA-β were significantly improved compared with before treatment(P<0.05).while there was no significant difference in metabolic indexes such as SBP,DBP,BMI,HDL-C,LDL-C,TC,TG(P >0.05).2.Compared with the healthy control group,the alpha diversity of the intestineal flora of newly diagnosed T2 DM patients decreased,and the beta diversity analysis showed that the overall structure of the intestinal flora was significantly contrasted and separated.Species difference analysis showed that the number of Proteobacteria,Escherichia-Shigella and Bacteroides in newly diagnosed T2 DM patients increased,while the Firmicutes and Bifidobacterium decreased(P<0.05).3.Compared with newly diagnosed patients with T2 DM,after 12 weeks of dapagliflozin treatment,the alpha diversity of intestinal flora increased,and Beta diversity analysis showed that there were significant differences in the overall structure of intestinal flora in patients before and after treatment.Compared with the different species before and after dapagliflozin,we found that the abundance of species of Gammaproteobacteria,Proteobacteria,Escherichia-Shigella,Acetobacterales,Acetobacteraceae,Enterobacteriaceae and Morganella decreased significantly after administration,while the abundance of species of Faecalibacterium prausnitziiz,Firmicutes,Oscillospiraceae,Dubosiella,and Alistipes increased significantly,and the differences were statistically significant(P<0.05).Spearman’s correlation analysis of intestinal flora and glycolipid metabolism indicators after dagliflozin treatment showed that Escherichia-Shigella were positively correlated with FBG and 2h PBG.Faecalibacterium prausnitziiz was negatively correlated with FBG,2h PBG and Hb A1 c.Oscillospiraceae were negatively correlated with FBG and2 h PBG.Alistipes were negatively correlated with 2h PBG.Conclusions:1.After the treatment of dapagliflozin in newly diagnosed patients with type 2diabetes,the blood glucose index decreased significantly,the insulin function was significantly improved.2.Patients with type 2 diabetes have a more disordered intestinal environment,and the number of short-chain fatty acid-producing bacteria and the increase of opportunistic pathogenic bacteria are its main characteristics.3.After the treatment of dapagliflozin in newly diagnosed patients with type 2diabetes,the composition of intestinal flora changed significantly,mainly manifested as an increase in short-chain fatty acid producing bacteria and a decrease in endotoxin-producing flora,suggesting that dapagliflozin may participate in blood glucose regulation by regulating intestinal microbiota.