title: Metabolic surgery and intestinal gene expression: Digestive tract and diabetes evolution considerations.
abstract: OBJECTIVE
  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 than 2 years, and a body mass index (BMI) of 30-35 kg/m(2) underwent metabolic surgery sleeve gastrectomy with transit bipartition between May 2011 and December 2011. Blood samples were collected pre and 3, 6 and 12 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 (520 kcal) and again 30, 60, 90, and 120 min after the meal to 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 6 mo postoperative, resulting in similar values 12 mo postoperatively (20-25 kg/m(2)). All of the patients experienced improved T2DM, with 7 patients (78%) achieving complete remission (HbA1c < 6.5%), and 2 patients (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 least 2 hypoglycemic drugs preoperatively. GLP-1 levels significantly increased after surgery (149.96 ± 31.25 vs 220.23 ± 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.
  
  
  CONCLUSIONS
  Metabolic surgery ameliorated diabetes in all of the patients, accompanied by increased anti-proliferative intestinal gene expression in non-excluded segments of the intestine.
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Marcos Ricardo da Silva
authors.initials: MR
authors.lastname: Rodrigues
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Marco Aurelio
authors.initials: MA
authors.lastname: Santo
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Giovani Marino
authors.initials: GM
authors.lastname: Favero
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Vieira
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Roberto Ferreira
authors.initials: RF
authors.lastname: Artoni
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: Nogaroto
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Egberto Gaspar
authors.initials: EG
authors.lastname: de Moura
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lisboa
authors.affiliation: Marcos Ricardo da Silva Rodrigues, Marco Aurelio Santo, Giovani Marino Favero, Elaine Cristina Vieira, Roberto Ferreira Artoni, Viviane Nogaroto, Egberto Gaspar de Moura, Patricia Lisboa, Fabio Quirillo Milleo, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, CEP 84030-900 Ponta Grossa, Paraná, Brazil.
authors.forename: Fabio Quirillo
authors.initials: FQ
authors.lastname: Milleo
mesh_terms: D000328:Adult; D050110:Bariatric Surgery; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics; D004386:Duodenum / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D005260:Female; D005743:Gastrectomy; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000601:surgery*; D019518:Postprandial Period; D012074:Remission Induction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C517652:hemoglobin A1c protein, human
keywords: Bariatric surgery; Diabetes mellitus; Gene expression; Hyperglycemia; Hyperplasia; Intestine