Epidemiological Study,bioinformatics Analysis And Related Mechanisms Of Metabolic Surgery For Type 2 Diabetes With BMI<35 Kg/m~2

Background:Type 2 diabetes(T2DM).and obesity have emerged as epidemic causing significant morbidity and mortality worldwide.Laparoscopic metabolic surgery has shown to be an effective treatment for obese patients with T2DM.However,little is known about the effectiveness of different laparoscopic surgery in Asia.The objective of this scoping review is to determine the impact of metabolic surgery for the treatment of T2DM in Asia and perform an evidence-based analysis.Methods:We searched PubMed for literature on laparoscopic metabolic surgery for the treatment of T2DM in Asia.Studies describing laparoscopic metabolic surgery for T2DM with or without obesity conducted in 48 Asian countries and three Asian sub-regions were included.There were no language restrictions.We excluded all studies from non-Asian countries,non-T2DM,and non-laparoscopic surgery.Three reviewers independently classified the included studies based on Oxford Center for Evidence-based Medicine guidelines.Results:In total 182 articles were identified.Most the studies were on clinical research(142),followed by basic science(33)and animal research(3).62.09%of the studies were from East Asia.The evidence of 11 studies were level I,52 were level II.Laparoscopic sleeve gastrectomy(LSG)was the main popular surgical procedure(64.90%)in Asia.The trends of studies and procedures on laparoscopic metabolic surgery for T2DM in Asian countries showed to increase over the last 8 years.We identified 16 studies on T2DM with BMI<35 kg/m~2 in Asia.Most of the studies were conducted in China.Laparoscopic Roux-en-Y gastric bypass(LRYGB)and LSG are the two main type surgical procedures performed for T2DM patients with obesity in Asia.Conclusion:Our results suggest that laparoscopic metabolic surgery is an effective and safe treatment for T2DM patients in Asia.However,further research is needed to identify the long-term complications,diabetes resolution,optimum procedures and promote metabolic surgery in Asia.Objective:More and more evidences suggested that metabolic surgery can also be used for BMI<35 kg/m~2 in patients with T2 DM.The main purpose of this study was to evaluate the safety and effectiveness of the two main surgical typies for T2 DM in patients with BMI<35 kg/m~2.Method:According to the PICO strategy of evidence-based medicine(EBM),the main clinical problems were put forward;the retrieval keywords and search strategies were designed,and then medical databases were searched.The level of evidence was used to identify and evaluate the evidences.Result: There 14 guidelines and six systematic reviews(Level evidences)were obtained.Domesic guidelines overall recommended that bariatric surgery could be performed for BMI=27.5~32.4 kg/m~2 with T2 DM.The abroad guidelines recommended that metabolic surgery should be considered as an option for adults with type 2 diabetes and BMI 30.0~34.9 kg/m~2(27.5~32.4 kg/m~2 in Asian Americans)if hyperglycemia is inadequately controlled despite optimal medical control by either oral or injectable medications(including insulin)(B recommendation level).And the indicators and follow-up were well described in the abroad guidelines.The lastest level I evidence about metabolic surgery compered with conservative treatment for BMI<35 kg/m~2 with T2 DM,this study included 11 RCTs contains 1090 Asian and Western patients,the follow-up time was 36 months,and the results showed that metabolic surgery as well as conservative treatment both could used for BMI<35 kg/m~2 with T2 DM,the major complication rate was 6.2~25.9%.(Level of evidence is I-1a),but the evidence was a little weaker,because did not evaluate the quality of included RCTs.Conclusion: Analysised and evaluated the the best evidence of the current research,the results showed that metabolic surgery could be used for BMI<35 kg/m~2 T2 DM in Asian patients.There has good effect on remission of diabetes,and Hb A1 c,BMI,lipids and other indicators were also obviously improved,there was no mortality,no severe complications,it was safe and effective.Objective: Adipocytes and their metabolism are closely related with obesity and diabetes,but the core gene and pathway still need to be explored.The aim of this study is to seek the core gene and pathway for adipocytes involved in obesity and diabetes from public databases using bioinformatics analysis.Methods: The GEO DataSets was searched using “diabetes” AND “obesity” AND “adipose” keywords.We began by sorting the data and then the differentially expressed genes(DEGs)between the diabetes/normal and/or obesity/no-obesity group,were determined using the GEO2 R analysis tool.STRING and Cytoscape software were used to visualize the protein-protein interaction of these DEGs.Bio GPS was performed to identify the expression of core genes on normal adipose tissues,Gene ontology(GO)and pathway were analyzed using Fun Rich software,and finally,the CTD web tool was performed to demonstrate relationships between core genes and potential diseases.Results: 22 human adipose samples,including ten from diabetic patients and 11 from normal tissues,were identified in this analysis.There were 184 DEGs,including 42 up-regulated genes and 142 down-regulated genes mainly enriched in metabolism,receptor activity,and collagen type IV,and glutamine biosynthesis I pathway by enrichment analysis.Seven hub genes were identified from the PPI network using STRING,Cytoscape software,Bio GPS,and CTD tool.Eventually,four core genes(COL4A2,ACACB,GLUL,and CD36)with high expression in adipose tissue and that were closely related to obesity or diabetes were selected.Conclusions: This bioinformatics analysis confirmed that DEGs and hub genes,such as COL4A2,ACACB,GLUL,and CD36 might be the core molecular biomarkers of obesity in patients with or without diabetes in subcutaneous adipose tissue.These results could provide strong evidence for future science or precise gene target therapeutically research in obese patients with or without type 2 diabetes.Objective: To investigate the expression of COL4A2,ACACB,GLUL and CD36 in human adipose tissue and its clinical significance.Methods: The adipose tissue of three normal weight patients(NW)with type 2 diabetes(DM)was observation group,another three normal weight(NW)with non diabetic(NDM)as control.The adipose tissue of three 25 kg/m~2 < BMI < 35 kg/m~2(overweight and obesity,OW)with type 2 diabete patients(DM)was observation,anothere three cases of 25 kg/m~2<BMI<35 kg/m~2(OW)with non diabete(NDM)as a control group.We extracted the human adipose tissue from the participants including: A subcutaneous adipose tissue.B adipose tissue close to greater curvature.C adipose tissue close to Pylorus.D adipose tissue close to lesser curvature.E adipose tissue close to jejunum mesangial.F adipose tissue close to ileum mesangial.HE staining was used to show the pathological characteristics of the adipose tissue in each group.The protein expression level of COL4A2,ACACB,GLUL and CD36 protein was detected by immunohistochemistry and Western Blot.qRT-PCR method was used to detect the RNA expression level of COL4A2,ACACB,GLUL and CD36 were detected by qRT-PCR.P<0.05 considered as a statistically significant difference,T test wasa used to compare each two groups.Results: HE staining showed that in the normal weight(NW)with type 2 diabetes(DM)group,the red cytoplasms were more than that in the normal weight(NW)without diabetes(NDM)group,but the difference was not significant in 25 kg/m~2<BMI<35 kg/m~2 group.It suggested that the adipose tissue of normal weight with or without diabetic may be different;type 2 diabetes may affect the morphological changes of adipocytes.qRT-PCR results showed that CD36 were high expression of mesojejunum adipose in normal weight(NW)or 25 kg/m~2<BMI<35 kg/m~2(OW)with type 2 diabetes(DM),and the expression was more significantly in normal weight group(NW).COL4A2,GLUL and ACACB were high expression of mesojejunum adipose tissue in normal weight(NW)or 25 kg/m~2<BMI<35 kg/m~2(OW).Immunohistochemical results showed that the positive expression rate of CD36 was relatively higher in normal weight(NW)with type 2 diabetes(DM)than compare group(NW/NDM),and COL4A2,GLUL and ACACB positive expression rate were high in normal weight without diabetes group(NW/DM).The qualitative and quantitative analysis of CD36,COL4A2,GLUL and ACACB protein was performed by Western blot technology.The results showed that CD36 had a high expression in normal weight with type 2 diabetes(NW/DM)group,and COL4A2 was highly expressed in normal jejunal mesangial group.Conclusion: COL4A2 protin was high expressed in mesojejunum adipose tissue of normal weight without diabetes group;CD36 protein was high in mesojejunum adipose tissue of normal weight with type 2 diabetes group.It indicated that COL4A2 and CD36 were closed relationship with type 2 diabetes;it speculates that laparoscopic metabolic surgery may alleviate type 2 diabetes mellitus through changing the related factors of jejunum adipose tissue.