| Objective:To detect the influence of different hypoglycemic drugs(acarbose and sitagliptin)on the intestinal microflora of type 2 diabetes(T2D)patients,and to explore the regulatory role of intestinal microflora in glucose metabolism.Methods:Thirty newly diagnosed T2 DM patients were recruited at Xinqiao Hospital,Army Medical University(Chongqing,China),and were randomized into four groups: acarbosaccharide monotherapy group(AC,n=8),sitagliptin monotherapy group(Sit,n=7),corresponding placebo control group(n=7-8).The starting dose of acarbose(Bayer Pharmaceutical Co.,Germany)was 50mg/time and 3 times/day.The dose of sitagliptin(MSD Sharp & Dohme,USA)was 100 mg/d.At the same time,it is recommended that all subjects maintain a low calorie intake of 25 kcal/kg per day throughout the treatment and maintain regular physical exercise(2.5 hours/week).Serum and stool samples of subjects were collected 2 months after treatment,and 16s-r DNA sequencing was used to analyze the effect of hypoglycemic drugs on T2 D patients' intestinal flora.Three fecal samples with obvious therapeutic effects were selected from each group and transplanted to germ free(GF)male mice.GF mice were fed with high fat for 8 weeks before fecal microbiota transplantation(FMT),and the body weight changes of the recipient mice were recorded weekly.FMT was followed by high-fat feeding for 2 weeks.After 2 weeks,the body weight changes of recipient mice were recorded,fasting blood glucose,glucose tolerance,insulin release test and other glucose metabolism indexes were detected,and the regulation effect of intestinal flora changed by acarbose and sitagliptin on glucose metabolism was analyzed.Results:Sitagliptin can change the composition of intestinal flora of T2 D patients,mainly by increasing the abundance of bacteroidetes in the intestinal flora and reducing the abundance of firmicutes.After transplanting the intestinal flora altered by sitagliptin into GF mice,although it had no significant effect on the body weight and insulin level of recipient mice,it significantly improved the abnormal glucose tolerance caused by high-fat feeding in sterile mice.Further,we found that the intestinal flora structure of the FMT receptor mice was similar to that of the T2 D donor patients,that is,bacteroidetes increased and firmicutes decreased,suggesting that these changes in the flora may be related to the improvement of glucose tolerance,and the specific mechanism remains to be further studied.Conclusion:In this study,it was found that the hypoglycemic drug sitagliptin had an important regulatory effect on the composition of intestinal flora,and the altered intestinal flora could significantly improve the glucose tolerance of sterile mice,indicating that the regulation of glucose metabolism through the change of flora may be a new hypoglycemic mechanism of sitagliptin.In addition,regulating the composition of intestinal flora and the functional changes caused by changes in its composition may be a potential way to improve glucose homeostasis.Objective:To assess circulating fetuin-B concentrations in subjects with different degrees of glucose tolerance,and to analyze the association of fetuin-B concentrations with insulin resistance and the first phase of glucose-stimulated insulin secretion.Methods:Plasma fetuin-B concentrations were analyzed in 149 subjects with normal glucose tolerance(NGT,n = 54),impaired glucose regulation(pre DM,n = 42)and newly diagnosed type 2 diabetes mellitus(n T2 DM,n = 53).Intravenous glucose tolerance tests(IVGTTs)and biochemical parameters were also assessed in all participants.Results:Plasma fetuin-B concentrations were significantly higher in n T2 DM patients compared with NGT and pre DM subjects(both P < 0.001),and positively correlated with FPG,2h PG,HOMA-IR,Hb A1 c,hs-CRP,FINS and TG(P < 0.05),but negatively correlated with AIR,AUC,GDI and fasting Belfiore index(P < 0.01).After adjusting for age and gender,all correlations remained statistically significant(P < 0.05).Multivariate logistic regression analysis revealed that plasma fetuin-B concentrations were significantly correlated with n T2 DM after controlling for age,gender,BMI,WHR,blood pressure and lipid profiles.Conclusion:Patients with n T2 DM have significantly higher concentrations of plasma fetuin B compared with NGT subjects,and plasma fetuin B is strongly associated with glucose and lipid metabolism,chronic inflammation,and first-phase glucose-stimulated insulin secretion and insulin resistance. |
PDF Full Text Request