Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2015; 21(22): 6990-6998
Published online Jun 14, 2015. doi: 10.3748/wjg.v21.i22.6990
Metabolic surgery and intestinal gene expression: Digestive tract and diabetes evolution considerations
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
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
Author contributions: Rodrigues MRS designed the research and wrote the paper; Milleo FQ designed the research, conducted the surgical procedures and collected the data; Vieira EC designed the research, analyzed the data and wrote the paper; Santo MA conducted the surgical procedures and reviewed the paper; Favero GM analyzed data, conducted laboratorial experiments and reviwed the paper; Nogaroto V, Artoni RF, Moura EG and Lisboa P conducted the laboratorial experiments and reviewed the paper.
Supported by Grants from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (Faperj) and Instituto de Pesquisas Aplicadas à Medicina (INSPAM), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação Araucária (Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Estado do Paraná), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Secretaria de Estado da Ciência, Tecnologia e Ensino Superior/Unidade Gestora do Fundo do Paraná (SETI/UGF).
Ethics approval: The study was reviewed and approved by the Ethics Committee at the Ponta Grossa State University.
Informed consent: All patients provided written informed consent prior to study participation.
Conflict-of-interest: The authors have no conflicts of interest to declare.
Data sharing: The technical appendix, statistical code, and dataset are available from the corresponding author at fqmilleo58@gmail.com. Data sharing consent was not obtained from the participants, but the presented data are anonymized, and the risk of identification is low. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Fabio Quirillo Milleo, MD, PhD, Laboratório Multidisciplinar da Universidade Estadual de Ponta Grossa-Campus Uvaranas, Avenida General Carlos Cavalcanti, 474, CEP 84030-900 Ponta Grossa, Paraná, Brazil. fqmilleo58@gmail.com
Telephone: +55-42-32229444
Received: December 7, 2014
Peer-review started: December 7, 2014
First decision: January 22, 2015
Revised: January 27, 2015
Accepted: April 9, 2015
Article in press: April 9, 2015
Published online: June 14, 2015
Processing time: 193 Days and 12.2 Hours
Abstract

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 than 2 years, and a body mass index (BMI) of 30-35 kg/m2 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/m2). 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.

CONCLUSION: Metabolic surgery ameliorated diabetes in all of the patients, accompanied by increased anti-proliferative intestinal gene expression in non-excluded segments of the intestine.

Keywords: Diabetes mellitus; Hyperglycemia; Intestine; Gene expression; Hyperplasia; Bariatric surgery

Core tip: This study shows an improvement in expression of antiproliferative genes of intestinal mucosa after type 2 diabetes mellitus amelioration promoted by metabolic surgery procedure. We make a link between this outcome and morphological changes in intestinal mucosa on diabetes, that occurs mainly by insufficient negative control of mucosal growth in hyperglycemia. Metabolic and bariatric surgery promotes dramatic amelioration of glucose metabolism in diabetic patients by not completely understood means. This paper highlights for the first time, the intestinal absorptive capacity as the main focus for research of diabetes amelioration after metabolic surgery procedures.