| Objective: To explore whether it is possible to correct intestinal flora imbalance,alter metabolic disorder and chronic inflammation in type 2 diabetes mellitus patients after taking sagliptin,and to provide evidence for its other function in addition to blood sugar decrease.And compare the inflammatory factors in serum and intestinal flora among the post-treatment group,the control group post-treatment of metformin and the control group of diet control and exercise whose HbA1 c meets the standard(HbA1c<7.0%).Methods: Twenty male patients with type 2 diabetes mellitus,whose HBA1 c ranged from 7.0% to 8.5% in the Department of Endocrinology,Affiliated Hospital of Inner Mongolia Medical University from January 1,2017 to December 1,2018,were selected as the experimental group.At the same time,20 male patients with type 2 diabetes mellitus who were treated with metformin and 20 male patients with type 2 diabetes mellitus whose blood sugar was controlled by diet and exercise alone were selected as the experimental group.The test group was treated with oral saxagliptin(5 mg/tablet,1 tablet/day)for 3 months,and HbA1c<7.0% was up to standard.After metformin treatment,metformin was taken regularly in the past 3 months;the simple diet control group did not take any hypoglycemic agents in the past 3 months and only controlled blood sugar through diet exercise.Blood samples and fecal specimens of saxagliptin before and after treatment with metformin treatment group and simple diet control group were collected.Clinical indicators for blood sample determination include fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c),liver function,renal function,triglyceride(TG),cholesterol(TC),high density lipoprotein(HDL-C),low density lipid Protein(LDL-C),fasting insulin function(FINS),fasting C-peptide(FCP),retinol binding protein 4(RBP4),homocysteine ??(HCY),free fatty acids(NEFA).Inflammatory factors associated with inflammation,tumor necrosis factor(TNF-α),C-reactive protein(CRP),interleukin-6(IL-6),endotoxin(LPS),and adiponectin(ADP)were measured by ELISA.The intestinal flora was obtained by high-throughput sequencing of the high-throughput sequencing of the 16 S rRNA gene in the V4 to V5 region of the fecal sample by high-throughput sequencing of the Illumina PE300 platform.Results(1)After 3 months of treatment with saxagliptin,FBG,HbA1 c,TG,TC,LDL-C,NON-HDL-C,CRP,LPS,TNF-α,IL-6,and HOMA-IR were all lower than before treatment.The HOMA-β and ADP levels were higher than before,and the difference was statistically significant(P<0.05).The general data of saxagliptin treatment group and metformin group and simple diet exercise group showed that there was no significant difference in age,gender,disease duration,body weight,BMI,waist circumference,hip circumference and waist-hip ratio between the three groups(P>0.05).The comparison of clinical indicators and serum inflammatory factors in the treatment group,metformin group and dietary exercise group showed that the levels of TG,CRP,LPS,TNF-a and IL-6 in the treatment group and metformin group were lower than those in the dietary exercise group,and ADP levels were higher than those in the dietary exercise group(P<0.05).(2)There were 80 stool samples in the diet and exercise control group before and after treatment with Saglitine and metformin.A total of 9890734 valid sequences were obtained.Four groups of fecal samples were clustered by Operational Classification Unit(OTU),and 2092 OTUs were obtained.The diversity analysis of intestinal flora and the analysis of intestinal flora at the level of flora and genus are based on the establishment of OTU.(3)The results of Alpha diversity analysis showed that the Chao1 index representing bacterial flora abundance in the treatment group was higher than that before treatment,suggesting that the bacterial flora abundance in stool samples increased after treatment with Saglitin;the Shannon index representing bacterial flora diversity was higher than that before treatment with Saglitin,and the Simpson index was lower than that before treatment with Saglitin,suggesting that patients after treatment with Saglitin had higher bacterial flora abundance than thatbefore treatment with Saglitin.The diversity of intestinal microorganisms increased.There was no significant difference in Chao1 index,Shannon index and Simpson index between the two groups(P>0.05),indicating that the abundance and diversity of intestinal flora in the two groups were similar.However,the Chao1 index of the two groups was higher than that of the simple diet and exercise control group and the Simpson value was lower than that of the simple diet and exercise control group,suggesting that the flora abundance and diversity of the simple diet and exercise control group were lower than those of the salgliptin treatment group and the metformin treatment group,and the difference was statistically significant(P<0.05).(4)The results of intestinal flora detection at the phylum level showed that 80 samples were dominated by Bacteroides and Firmicutes,while the other major bacteria were Proteobacteria,Actinobacteria,Fusobacteria,Verrucomicrobia and Tenericutes.Compared with before treatment,the number of Firmicutes increased and the number of Bacteroides decreased after treatment(P<0.05).In addition,after treatment,Proteobacteria and Fusobacteria decreased,while Verrucomicrobia increased significantly(P<0.05).Compared with the other two groups,the levels of Fusobacteria and Bacteroides were higher in the simple diet and exercise control group than in the other two groups,while those in the Firmicutes,Verrucomicrobia and Tenericutes were lower than those in the other two groups.Abundance analysis of intestinal flora samples at generic level showed that after treatment,Faeccalibacterium,Magmonas,Roseburia,Ruminococcus,Blautia,Bifidobacterium,Lactobacillus,Akkermansia,Eubacterium coptanoligenes increased,while Bacteroides,Escheria-Shigella,Prevotello,Klebsiella increased.The difference was statistically significant(P<0.05).It is worth mentioning that Akkermansia was found in the intestine of patients after treatment with Shaglitin,but it did not appear before treatment with Shaglitin.Escherichia-Shigella in the simple diet and exercise control group was higher than that in the shaglitin treatment group and metformin treatment group,Blautia,Lactobacillus and Roseburia were lower than those in the two groups,and Ruminococcus was lower than that in the shaglitin treatment group(P< 0.05).Conclusions:(1)Sagliptin can reduce FBG,HbA1 c,TG,TC,LDL-C,NON-HDL-C,HOMA-IR and other indicators of type 2 diabetes mellitus,and improve HOMA-β and its glycolipid metabolism and insulin resistance;(2)The levels of serum inflammatory factors TNF-a,IL-6,CRP and LPS in the simple diet control group were higher than those in the shaglitin treatment group,the metformin treatment group,the ADP anti-inflammatory factor was lower than those in the shaglitin treatment group and the metformin treatment group,while HbA1 c in the three groups was less than 7%.This suggests that the mechanism of shaglitin and metformin improving inflammation in patients with type 2 diabetes may be independent of hypoglycemia;(3)Sagliptin can reduce TNF-α,IL-6,CRP and LPS inflammatory factors in type 2 diabetes mellitus,increase ADP anti-inflammatory factors and improve the chronic inflammatory state of the body;(4)There was no significant difference in serum inflammatory factors TNF-α,IL-6,CRP,LPS,ADP between the metformin treatment group and the salgliptin treatment group,indicating that metformin also had the effect of improving inflammation in type 2 diabetes mellitus;(5)The beneficial bacteria such as Lactobacillus in the intestinal flora of the simple diet and exercise group were slightly lower than those of the treatment group and metformin group;Escherichia-Shigella conditioned pathogenic bacteria were slightly higher than those of the treatment group and metformin group,indicating that the effect of the control of diet and exercise on the improvement of intestinal microbial structure in type 2 diabetes mellitus patients was greater than that of the control of diet and exercise alone;(6)After treatment,the abundance of beneficial bacteria such as Faecalibacterium and Lactobacillus(belonging to Gram-positive bacteria)in Phytoplasma and its subphylum was increased,and the abundance of conditional pathogenic bacteria such as Bacteroides,Prevotella and Escherichia-Shigella and Klebsiella(belonging to Gram-negative bacteria)in Phytoplasma and Proteobacteria was decreased mainly by increasing the abundance of beneficial bacteria such as Faecalibacterium and Lactobacillus(belonging to Gram-positive bacteria).To improve the structure of intestinal flora in patients withtype 2 diabetes mellitus;(7)The composition of most intestinal flora in phylum and genus after metformin treatment was not significantly different from that after salglistine treatment.Metformin can also improve intestinal flora disorders in type 2diabetes mellitus. |
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