Simulation of gastric bypass effects on glucose metabolism and non-alcoholic fatty liver disease with the Sleeveballoon device

James, Casella-Mariolo, Lidia, Castagneto-Gissey, Giulia, Angelini, Andrea, Zoli, Pierluigi, Marini, Stefan R., Bornstein, Dimitri J., Pournaras, Francesco, Rubino, Carel W., le Roux, Geltrude, Mingrone, Giovanni, Casella

EBioMedicine |

Background: Gastric bypass surgery is a very effective treatment of obesity and type 2 diabetes. However, very few eligible patients are offered surgery. Some patients also prefer less invasive approaches. We aimed to study the effects of the Sleeveballoon – a new device combining an intragastric balloon with a connecting sleeve, which covers the duodenal and proximal jejunal mucosa – on insulin sensitivity, glycemic control, body weight and body fat distribution. Methods: We compared the effects of Sleeveballoon, Roux-en-Y Gastric-Bypass (RYGB) and sham-operation in 30 high-fat diet (HFD) fed Wistar rats. Whole body and hepatic insulin sensitivity and insulin signaling were studied. Transthoracic echocardiography was performed using a Vevo 2100 system (FUJIFILM VisualSonics Inc., Canada). Gastric emptying was measured using gastrografin. Findings: Hepatic (P =.023) and whole-body (P =.011) insulin sensitivity improved in the Sleeveballoon and RYGB groups compared with sham-operated rats. Body weight reduced in both Sleeveballoon and RYGB groups in comparison to the sham-operated group (503.1 ± 8.9 vs. 614.4 ± 20.6 g, P =.006 and 490.0 ± 17.7 vs. 614.4 ± 20.6 g, P =.006, respectively). Ectopic fat deposition was drastically reduced while glycogen content was increased in both liver and skeletal muscle. Gastric emptying (T1/2) was longer (157.7 ± 29.2 min, P =.007) in the Sleeveballoon than in sham-operated rats (97.1 ± 26.3 min), but shorter in RYGB (3.5 ± 1.1 min, P <.0001). Cardiac function was better in Sleeveballoon and RYGB versus sham-operated rats. Interpretation: The Sleeveballoon reduces peripheral and hepatic insulin resistance, glycaemia, body weight and ectopic fat deposition to a similar level as RYGB, although the contribution of gastric emptying to blood glucose reduction is different.