Tu1478 Risk Factors Associated With Post-Operative Complications After Gastric Bypass: A Nationwide Analysis

Abstract

be hyperplasic after RYGB surgery in murine models, can improve glucose homeostasis by increasing its own glucose requirements. Aim: To evaluate in rats and humans how the remodeling of the gut epithelium after RYGB impacts on absorption and consumption of sugar by the alimentary Roux limb. Methods: High-fat diet-induced obese male Wistar rats were randomly assigned to RYGB or sham surgery. Two weeks later, jejunum, alimentary Roux and bypassed limbs were collected to perform histological analyses and evaluate relative mRNA levels (qPCR) and protein expression (immunostaining) of sugar transporters (GLUTs and SGLT-1). Glucose transport and consumption were assayed using ex vivo jejunal loops everted (serosal to luminal) or not (luminal to serosal), with [14C]-glucose as substrate, mimicking blood and dietary sugar transport, respectively. Non parametric Mann-Whitney tests were used to compare sham and RYGB. Histological analyses and immunostaining of Ki-67 and GLUT1 were performed on formalin-fixed Roux limb sections obtained from RYGB patients that underwent reoperation for late complications. Perioperative samples of obese patients were used as control. Roux limb glucose consumption was assayed post operatively by PET/CT scan imaging. For all procedures, patient's written consent was obtained. Results: RYGB surgery in obese rats recapitulates the beneficial effects seen in humans including improvement of glucose homeostasis. Histological analyses of the alimentary Roux limb revealed a hyperplasic mucosa with a dramatic increased number of Ki67proliferating cells in the crypts [a]. 60 min after luminal or serosal loads of [14C]-glucose in rat jejunal loops, higher amounts of [14C]-glucose were found in the Roux limb [b] (+150% or +400% vs. sham, P<0.001) suggesting an increased glucose consumption. Similarly, increased [18F]-FDG uptake by the Roux limb was observed in RYGB patients by PET/ CT scanning. In rats, the relative mRNA expression pattern of intestinal sugar transporters was dominated by Glut1 [c] (x3 P<0.05 vs. sham). This was confirmed by a strong immunolabeling of GLUT1 protein at the villi's top both in RYGB rats and humans. Conclusions: RYGB surgery induces an overgrowth of the alimentary limb in humans. This adaptive mechanism requires energy and induces reprogramming of sugar metabolism exemplified by GLUT1 expression. By increasing dietary and blood glucose consumption, the rearranged gut could improve glucose disposal during and betweenmeals and contribute to diabetes resolution.