The Clinic And Basic Reasch Of Laparoscopic Gastric Bypass Surgery For Type 2 Diabetes Mellitus

Part I The clinical effectiveness and safety of laparoscopic gastric bypass surgery in the treatment of type 2 diabetes mellitusObjective: To discuss the clinical effectiveness and safety of laparoscopic gastric bypass(LRYGB)in surgical treatment of type 2 diabetes mellitus(T2DM).Methods: Retrospectively analyzed the data of 73 patients with type 2 diabetes mellitus who underwent LRYGB in the first affiliated hospital of Soochow University from May 2010 to February 2012.Among them,36 patients had finished a 5-year period of follow-up survey.The patients were divided into 2 groups,the high-BMI(body mass index)group(BMI > 27.5)and the low-BMI group(BMI ≤ 27.5).Clinical data of patients,such as the length of hospital stay,operative time,blood loss,surgical operation related complications were recorded.All patients were subjected to follow-up controls with anthropometric and metabolic indices,such as weight,BMI,waist circumference,fasting blood-glucose(FBG)and oral glucose tolerance test(OGTT),HbA1 c,C peptide,serum insulin,blood lipids and the change of diabetes complications,etc,at 0.5,1,2,3 and 5 years after surgery.Results: All patients were discharged smoothly after surgery without perioperative death and surgery related complications were 11%(8/73).The FBG,HbA1 c,weight,BMI,waist circumference,serum triglyceride and cholesterol of the patients were declined significantly(P < 0.05)and rapidly after the operation.76.2%(16/21)of the high-BMI group patients and 40.0%(6/15)of the low-BMI group patients with type 2 diabetes mellitus got remission after the surgery 5 years later.The difference between the remission rate of the two groups was statistically significant(P < 0.05).Pre-operatively,the differences of BMI,waist circumference,course of T2 DM,2 hours postprandial blood glucose and 2 hours postprandial blood C peptide between the remission group and the improvement group were statistically significant(P < 0.05).Conclusions: LRYGB can be performed safely on obese or non-obese patients with type 2 diabetes mellitus without severe complications.The effect is better in obese patients than in non-obese patients.LRYGB can effectively reduce the weight,control blood glucose and lipid levels in the patients with T2 DM.The long-term effect is stabilization during 5 years.Pre-operatively,the BMI,waist circumference,course of T2 DM,2 hours postprandial blood glucose and 2 hours postprandial blood C peptide may be use as predictive indicators of the effectiveness of LRYGB.Part II Changes of the expression levels of patients’ peripheral blood microRNAs after receiving laparoscopic gastric bypass as a treatment for type 2 diabetes mellitusObjective: To study the effectiveness of laparoscopic gastric bypass(LRYGB)surgery on the expression levels of type 2 diabetes mellitus(T2DM)patients’ peripheral blood microRNAs(miRNAs).Methods: MiRNA microarray system was used to identify the expression levels of 1 high-BMI group T2 DM patient’s peripheral blood miRNAs before and 1 year after receiving LRYGB surgery.Refer to the relevant literature and data,the miRNAs that related to glucolipid metabolism and whose expression level had altered after surgery were chosen for further analysis.To certify whether the expression level of these miRNAs had altered or not,Real-Time qPCR was used to test the 15 patients’ samples,who had received surgical treatment.Results: The miRNA microarray data showed 70 miRNAs upregulated and 74 miRNAs downregulated after RYGB in 1 patient of the high-BMI group.Hsa-miR-29a-3p,hsa-miR-122-5p,hsa-mi R-124-3p,and hsa-miR-320 a were chosen for Real-Time qPCR test.Hsa-miR-29a-3p was downregulated in 10 patients with T2 DM and 2 morbidly obese patients,and upregulated in 1 patient with T2 DM postoperatively compared with the preoperative period.hsa-miR-122-5p was downregulated in 10 patients with T2 DM and upregulated in 2 morbidly obese patients.hsa-miR-124-3p was downregulated in 10 patients with T2 DM and upregulated in 2 patients with T2 DM.hsa-miR-320 a was downregulated in 11 patients with T2 DM and 1 morbidly obese patient,and upregulated in 1 patient with T2 DM and 2 morbidly obese patients.Conclusions: LRYGB may alter the expression level of miRNAs.Hence,LRYGB could regulate the function of synthesis and secretion of insulin of pancreatic β-cell and insulin sensitivity of tissue cell,throuh controlling the function of the target gene of miRNA.MiRNAs can be used as an effective auxiliary factor of evaluation of the pancreatic islet function preoperatively and prediction in the LRYGB therapeutic effect.Part III Role of laparoscopic gastric bypass in regulating methylation rate of micro RNA gene promoterObjective: To study the effect of laparoscopic gastric bypass(LRYGB)on methylation rate of type 2 diabetes mellitus(T2DM)patients’ peripheral blood microRNA(miRNA)gene promoters.Methods: Bisulfite sequencing PCR(BSP)was used to detect methylation rate of hsa-miR-29a-3p,hsa-miR-122-5p,hsa-miR-124-3p and hsa-miR-320 a gene promoter of 1 high-BMI group T2 DM patient’s peripheral blood DNA samples before and 1 year after surgery.The methylation state of the CpG sites within an approximately 400 bp genomic DNA fragment of each of the four miRNA genes,including about 200 bp upstream and 100 bp downstream of the pre-miRNA was detected.Results: Hsa-mi R-124-3p and hsa-miR-320 a genes locate in CpG islands,and hsa-miR-29a-3p and hsa-miR-122-5p gene promoters are out of the genomic DNA fragment that had been detected.There were no statistical significant differences of the methylation rate of the CpG sites around the 4 pre-miRNA genes between before and after LRYGB surgery(P > 0.05).Conclusions: The methylation rate of the CpG sites around hsa-miR-124-3p and hsa-miR-320 a genes may affect their expression levels.LRYGB regulated the expression level of miRNA,without changing the methylation rate of miRNA gene promoter.