Adaptação digestiva com duodenal switch parcial em pacientes diabéticos e com IMC<35 Kg/m2. Análise da resposta clínica, laboratorial, enterohormonal e da expressão do gene p53 na mucosa intestinal

Abstract

Diabetes mellitus type 2 (DM2) is a worldwide increasing prevalence disease, being related to a variety of comorbidities. The relationship between the digestive tract and DM2 has been strengthened by the results of different metabolic surgery procedures on resolution of the endocrine disorder, before weigh loss achievement. Hypertrophic morphological changes in the intestinal epithelium are observed in the early stages of disease development and seems to have a pivotal role in the establishment of chronic hyperglicemia. The p53 gene directly participates on regulation of growth processes of the intestinal epithelium, and its expression has been shown to be altered in diabetic states.The objectives were to evaluate clinical and laboratory results in DM2 patients, presenting Body Mass Index(BMI)>25 and <35Kg/m2, undergoing a metabolic surgery procedure called digestive adaptation with partial duodenal switch(DSP). To assess p53 gene expression behavior in intestinal mucosa, on pre and postoperative period. Nine patients presenting DM2 and BMI below 35Kg/m2 underwent DSP.Biopsies of the duodenum and intermediate portion of the ileum were undertaken in diabetic state (pre and transoperative respectively) and 3 months after surgery by upper gastrointestinal endoscopy. The evolution of anthropometric (BMI) and laboratory parameters were acessed on postoperative period. Serum levels of enterohormones glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic peptide (GIP) were determined by the method enzyme-linked immunosorbent assay (ELISA), pre and postoperatively, on fasting and postprandial state (30',60'90 and 120') after ingestion of a standart meal.The p53 gene expression was evaluated by real time polymerase chain reaction (qrt-PCR) and western blot, on two different periods. The variables: fasting and postprandial (2 hours) glicemia, fasting triglycerides (TG), glycosylated hemoglobin (HbA1c) and C-peptide were undertaken. The mean levels of laboratorial parameters were compared by mulivariate analyses (ANOVA) and Tukey test. The mean expression of the p53 gene was compared in two different periods by T test. Between may and December 2010, four men and 5 women were operated on. The mean BMI was 31,1. There was a decrease in BMI of 23% after one year of surgery. There was a significant decrease (p<0,05) on fasting TG and HbA1c levels as well as glucose levels on fasting and postprandial state (2 hours) when compared pre and postoperatively. There was an increase (p<0,05) in C-peptide levels after surgery. Serum levels of GLP-1 were significantly higher postorperatively (p<0,05), on both fasting and postprandial condition, and there was a decrease,not significant, on GIP levels. The p53 relative gene expression showed a significant increase (p<0,05) in the postoperative period in duodenal mucosa (transcriptional state) and showed an increasing trend in the ileum, but not statistically significant. Only ileum portion results were succesfully acessed by western blot analisys, showing an increasing trend as well. The DSP procedure was succesfully capable to control type 2 diabetes in patients presenting BMI<35 Kg/m2. There was a significant enhancement of GLP-1 secretion and a decreasing trend for GIP on postoperative period. There was increased expression of mucosal p53 in the postoperative period after the control of DM2, when compared to diabetic pre-operative state.