Measures of glucose homeostasis during and after duodenal exclusion using a duodenal-jejunal bypass liner in a normoglycemic,nonobese canine model

BackgroundDiscovering the role duodenal exclusion plays in weight loss and resolution of type 2 diabetes (T2D) may help refine the surgical and nonsurgical treatment of obesity and T2D.ObjectivesTo assess changes in glucose homeostasis due to duodenal exclusion using a duodenal-jejunal bypass liner (DJBL) in a nonobese canine model.SettingAcademic laboratory setting.MethodsAn intravenous glucose tolerance test (IVGTT), and a mixed-meal tolerance test (MMTT) at baseline, 1, and 6 weeks post DJBL implantation (I1 and I6, respectively), and 1 and 6 weeks post DJBL removal (R1 and R6, respectively) were done in canines (n = 7) fed a normal chow diet.ResultsPlacement of the DJBL induced weight loss that was maintained until 4 weeks post removal (R4), despite normal food intake. Total bile acids (TBA) and glucagon-like peptide-1 (GLP-1) during the MMTT were significantly increased at I1 and were associated with increased lactate and free fatty acids. Hypoglycemia counter-regulation was blunted during the IVGTT at I1 and I6, returning to baseline at R1. While there were no changes to insulin sensitivity during the experiment, glucose tolerance was significantly increased following the removal of the DJBL at R1.ConclusionThese data show that in a normoglycemic, nonobese canine model, duodenal exclusion induces energy intake-independent weight loss and negative metabolic effects that are reversed following re-exposure of the small intestine to nutrients.