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

Objective:To detect whether the intestinal environment of newly diagnosed T2 DM patients has changed compared with healthy people,and to detect the effect of subcutaneous injection of dulaglutide on the intestinal flora of newly diagnosed T2 DM patients,so as to explore whether dulaglutide can affect the prognosis of T2 DM by changing the structure of intestinal flora.Methods:From June 2021 to June 2022,11 patients with newly diagnosed T2 DM who were treated in the Endocrinology Department of the 920 th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army were selected as the dulaglutide treatment group.Ten healthy subjects with matched age and body mass index(BMI)served as normal control group.Stool samples were collected from the normal control group,and stool samples and clinical data were collected before and after dulaglutide treatment.Data Clinical data include body weight(WG),BMI,fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fasting C-peptide(FC-P),postprandial 2 Hour C-peptide(2HCP),total cholesterol(TC),total triglycerides(TG),low-density lipoprotein(LDL),highdensity lipoprotein(HDL),homeostasis model assessment of insulin resistance index(HOMA-IR)with homeostasis model assessment of beta cell function index(HOMABeta).Stool specimens were analyzed by 16 Sr RNA gene sequencing to compare the changes in intestinal flora composition of newly diagnosed T2 DM patients with the clinical data and intestinal flora structure of the study subjects before and after dulaglutide intervention,and Spearman correlation was used to analyze the correlation between glucose-lowering effect and intestinal flora structure.Results:1.Decrease in WG,BMI,TC,TG,LDL,HbA1 c,FBG,PBG and increase in HDL,FC-P,2HC-P after 3 months of dulaglutide treatment compared to baseline.2.The results of alpha diversity analysis of stool samples showed that the alpha diversity of gut microbes decreased in patients with newly diagnosed T2 DM,and increased in dulaglutide-treated patients.The overall structure of the intestinal flora of the newly diagnosed T2 DM patients was significantly separated from the healthy control group and the dulaglutide treatment group.3.The results of 16 Sr RNA gene sequencing showed that the dominant bacterial phyla were Firmicutes and Bacteroidetes.Compared with the healthy group,newly diagnosed T2 DM patients increased the phylum of Bacteroides and the ratio of Firmicutes/Bacteroidetes decreased,and the difference was statistically significant(all P<0.05).Bacteroides and Bacteroidetes increased,Proteobacteria decreased(all P<0.05).4.Compared with healthy people,the first episode of T2 DM patients increased Blautia,Ruminococcus and Erysipelothrix(all P<0.05).5.The results of Lefse analysis showed that there were 16 high-dimensional biomarkers in the dulaglutide group before treatment,and 12 high-dimensional biomarkers in the post-treatment group.6.The results of Spearman correlation analysis showed that the abundance of Escherichia coli was positively correlated with HbA1 c,FBG and PBG.The abundance of faecalibacterium was negatively correlated with WG,BMI,HbA1 c,FBG and PBG.The abundance of Bacteroides was negatively correlated with HbA1 c,FBG and PBG.The abundance of Klebsiella was positively correlated with HbA1 c,FBG and PBG.The abundance of Roseburia was negatively correlated with FBG.The abundance of Blautia was positively correlated with HbA1 c,FBG and PBG.The abundance of Lachnospiraceae＿unclassified was negatively correlated with HbA1 c and FBG.The abundance of Ruminococcus was positively correlated with HbA1 c and FBG.The abundance of Erysipelothrix was positively correlated with HbA1 c and FBG.(all P<0.05).Conclusions:1.Dulaglutide reduced body weight and improved blood glucose and islet β-cell function in newly diagnosed T2 DM patients.2.The disturbance of intestinal microbiota balance in newly diagnosed T2 DM patients may be related to the increased abundance of opportunistic pathogenic bacteria such as Blautia,Ruminococcus,and Erysipelothrix.3.Dulaglutide can improve the balance of intestinal flora in patients with newly diagnosed T2 DM by increasing the abundance of beneficial bacteria producing shortchain fatty acids such as Roseburia,Faecalibacterium,and Bacteroides and reducing the abundance of conditional pathogenic bacteria such as Escherichia coli,Klebsiella,Blautia and Erysipelothrix.These results suggest that dulaglutide may regulate the prognosis of T2 DM by changing the structure of intestinal microbiota.