Metabolic surgery and intestinal gene expression:Digestive tract and diabetes evolution considerations

摘要

AIM: To investigate the effects of bariatric surgery on metabolic parameters, incretin hormone secretion, and duodenal and ileal mucosal gene expression.METHODS: Nine patients with type 2 diabetes mellitus(T2DM), chronic serum hyperglycemia for more than2 years, and a body mass index(BMI) of 30-35 kg/m2 underwent metabolic surgery sleeve gastrectomy with transit bipartition between May 2011 and December2011. Blood samples were collected pre and 3, 6 and12 mo postsurgery. Duodenal and ileal mucosa samples were collected pre- and 3 mo postsurgery. Pre- and postoperative blood samples were collected in the fasting state before ingestion of a standard meal(520kcal) and again 30, 60, 90, and 120 min after the mealto determine hemoglobin A1c(HbA1c) levels and the lipid profile, which consisted of triglyceride and total cholesterol levels. Intestinal gene expression of p53 and transforming growth factor(TGF)-β was analyzed using quantitative reverse-transcription PCR. Gastric inhibitory polypeptide(GIP) and glucagon-like peptide-1(GLP-1)were quantified using the enzyme-linked immunoassay method and analyzed pre- and postoperatively.Student's t test or repeated measurements analysis of variance with Bonferroni corrections were performed as appropriate.RESULTS: BMI values decreased by 15.7% within the initial 3 mo after surgery(31.29 ± 0.73 vs 26.398± 0.68, P < 0.05) and then stabilized at 22% at 6mo postoperative, resulting in similar values 12 mo postoperatively(20-25 kg/m2). All of the patients experienced improved T2 DM, with 7 patients(78%)achieving complete remission(HbA1c < 6.5%), and 2patients(22%) achieving improved diabetes(HbA1c< 7.0% with or without the use of oral hypoglycemic agents). At 3 mo postoperatively, fasting plasma glucose had also decreased(59%)(269.55 ±18.24 mg/dL vs 100.77 ± 3.13 mg/dL, P < 0.05)with no further significant changes at 6 or 12 mo postoperatively. In the first month postoperatively,there was a complete withdrawal of hypoglycemic medications in all patients, who were taking at least2 hypoglycemic drugs preoperatively. GLP-1 levels significantly increased after surgery(149.96 ± 31.25 vs220.23 ± 27.55)(P < 0.05), while GIP levels decreased but not significantly. p53 gene expression significantly increased in the duodenal mucosa(P < 0.05, 2.06 fold)whereas the tumor growth factor-β gene expression significantly increased(P < 0.05, 2.52 fold) in the ileal mucosa after surgery.CONCLUSION: Metabolic surgery ameliorated diabetes in all of the patients, accompanied by increased antiproliferative intestinal gene expression in non-excluded segments of the intestine.