The Clinical And Mechanism Research Of Metabolic Surgery

The metabolic syndrome has become a worldwide epidemic which mainly clinical manifestations were obesity and type 2 diabetes. Traditional treatment methods such as diet control, exercise, medication can not achieve lasting satisfactory effects in some patients. In recent years, surgical were developed as the novel methods for treating metabolic syndrome, along with the Metabolic Surgery rising. With the incidence of metabolic syndrome increased year by year in China, it is urgently needed to increase the operative level and enhance the size of Metabolic Surgery. However, because of the relative late starte of Metabolic Surgery in China,along with the difference of ethnic and diet habits between China mainland population and reported other populations, many critical issues need to be resolved such as the choice of surgical procedures, the evaluation of surgical effectiveness and safety, and the mechanism of metabolism improvement after metabolic surgery.There are few reports on metabolic surgery effectiveness in China mainland population at present. Because the metabolic syndrome features were associated with ethnic, geographical environment, lifestyle, diet and other factors, the experience in publised reports in other countries and regions could not suitable for China mainland population. It is urgently needed to summary the effectiveness and surgical experiences for China mainland population. On the other hand, the LAGB, LSG, and LRYGB, which were the main surgical procedures clinical practiced currently, have different characteristics. At present, the choice of surgical procedures mainly depends on the habits of surgeons and patients’ wishes, in which the objective evidence was lack. Though the effectiveness of metabolic surgery has been widely accepted, its mechanism of metabolism improving remained unknow. Breaking results of the the mechanism of metabolic surgery may provide a new target for the treatment of metabolic syndrome, and provide the theoretical basis and ideas for the development of novel safe and efficient treatment methods.To study the effectiveness and the possible mechanism of metabolic surgery for of China mainland population, we conducted the present project, which collected and perform retrospective analysis the metabolic surgery cases in the Changhai Hospital,Second Military Medical University. In addition, we established type 2 diabetes(diabetes mouse db) mouse gastric sleeve resection model to investigate the mechanism of glucose metabolism improvement postoperative.PART I: Comparative study of the effectiveness of three metabolic surgical procedures to treat obese patients with type 2 diabetesObjective: We analyzed LAGB, LSG, LRYGB surgical treatment cases for obese patients with type 2 diabetes retrospectively, to provide a theoretical basis for choice of the metabolic surgical procedures.Methods: The cases of obese patients with type 2 diabetes were collected, who admitted to surgical treatment in the department of general surgery, the First Affiliated Hospital of the Second Military Medical University(Changhai Hospital)from January 2010 to December 2011. The clinnical information and 3 years of follow-up data were analyzed retrospectively for comparison the weight loss and hypoglycemic effectiveness between different sugical procedure.Results: A total of 43 patients enrolled, of whom 14 patients underwent LAGB,13 patients underwent LSG, and 16 patients underwent LRYGB. There was no significant differences in the general conditions between three groups. LAGB showed shorter operative time and less bleeding than the other two procedures. The effectiveness of LSG and LRYGB were similar evaluated by a variety of indicators,both of which were better than LAGB. Evaluated using body weight and BMI index,the effectiveness of LAGB group showed statistically significant difference with LRYGB group after 6 months post-operative. Similarly, the effectiveness of LAGB group showed statistically significant difference with LSG group after 24 months post-operative, while there was no statistically significant between LSG group and LRYGB group. Evaluated using EWL%, the effectiveness of LAGB group showed statistically significant difference with LRYGB group after 1 month post-operative.Similarly, the effectiveness of LAGB group showed statistically significant difference with LSG group after 3 months post-operative, while there was no statistically significant between LSG group and LRYGB group except for the 1month and the 6 month time point. The effectiveness of LAGB group showed statistically significant difference with LRYGB group after 12 months post-operative evaluated by waist circumference index. Similarly, the effectiveness of LAGB group showed statistically significant difference with LSG group after 24 months post-operative, while there was no statistically significant between LSG group and LRYGB group. The hypoglycemic effect of LAGB was weaker than LSG and LRYGB procedure evaluated by FPG index, which showed significant differenceafter 3 months post-operative. Evaluated by Hb A1c% index, the hypoglycemic effect of LAGB was weaker than LSG and LRYGB procedure, which showed significant difference after 12 months post-operative. There was no statistically significant between LSG group and LRYGB group evaluated by any index.Conclusion: For obesity patients with type 2 diabetes in China mainland population, the weight loss and hypoglycemic effectiveness in 3-years post-operative was similar between LSG and LRYGB procedures, both of which were superior to LAGB surgical procedures.PART II: The clinical study of laparoscopic gastric sleeve resectionObjective: We evaluate the effectiveness of LSG for China mainland patients, to accumulate experience and provide a theoretical basis for the choice of surgical procedures.Methods: Retrospective analysis of patients submitted to LSG in the department of general surgery, the First Affiliated Hospital of the Second Military Medical University(Changhai Hospital) between January 2011 and February 2012 was performed. Medium-term outcome measures were total weight loss(%TWL), excess weight loss(%EWL), co-morbidities improvement and complications.Results: Seventy patients(BMI 40.8±5.9 kg/m2) underwent LSG, comprising40 females and 30 males. The most common comorbidity was diabetes(29/70,41.4%). Lost to follow-up for weight loss was 15.7%, 31.4% and 41% at 1, 2 and 3years. The %TWL was 34.4±6.1, 34.7± 6.2 and 33.7±7.1 at 1, 2 and 3 years.The %EWL increased to 77.1±13.0, 77.9±12.2 and 77.2±13.1 at 1, 2 and 3 years.The proportions of patients having successful weight loss were 100% or 85% at 3years according the definition of %TWL>10% or %EWL>50%. Approximately79.3%, 51.7% and 44.8% of patients completed follow-up for glycemic control at each time point. The proportions of patients with optimal glycemic control(FBG<5.6 mmol/L; A1C<6.5%) were 47.9%, 60.0% and 69.2% at 1, 2 and 3 years.The weight loss and glycemic control effect may be greater in the high BMI group(≥40 kg/m2). Early and late complications occurred in 8.6% and 7.1% of patients during follow-up.Conclusion: LSG is effective and safe for China mainland obese patients. The weight loss effectiveness was better for the patients with BMI≥40 kg/m2, while the hypoglycemic effectiveness was better for the patients with BMI≥40 kg/m2.PART III: The mechanisms of sugar metabolism improvement after the stomach sleeve resectionObjective: We established a db/db mice gastric sleeve resection model to investigate mechanisms of glucose metabolism improvement post VSG surgery.Methods: 50 db/db mice were randomly assigned to VSG surgery and Sham surgery group. Weight and glucose metabolism related indicators were observed and detected in 2 months after surgery. HE staining, immunohistochemistry, RT-PCR analysis were performed to analyze the change of pancreas, liver and intestinal tissue morphology, as well as expression level of glucose metabolism-related critical molecules in the mice.Results: 21 mice survived in VSG group, while 23 mice survived in Sham group. There was no significant difference in weight and food intake post-operative between the two groups. The glucose metabolism was improved more significantly in VSG group than Sham group. There was no significant difference in the islet morphology of two groups. The distribution of functional cells in islets was improved better in VSG group than Sham group. The GLP-1 expression level in intestinal segments was higher in VSG groupthan Sham group. Similarily, the FXR expression level in liver, jejunum and ileum increased in VSG group compared with Sham group.Conclusion: We established the db / db mice VSG metabolic surgery model whcih excluded the hypoglycemic effect of body weight changes. The mechanism of glucose metabolism improvement post VSG surgery could related to the improvement of islet functional cell distribution, GLP-1 expression increasing in intestinal, and the expression of FXR increasing in liver, jejunum and ileum.