Laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy: 5-year outcomes of merged data from two randomized clinical trials (SLEEVEPASS and SM-BOSS).

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (LRYGB) are both effective surgical procedures to achieve weight reduction in patients with obesity. The trial objective was to merge individual-patient data from two RCTs to compare outcomes after LSG and LRYGB. METHODS: Five-year outcomes of the Finnish SLEEVEPASS and Swiss SM-BOSS RCTs comparing LSG with LRYGB were analysed. Both original trials were designed to evaluate weight loss. Additional patient-level data on type 2 diabetes (T2DM), obstructive sleep apnoea, and complications were retrieved. The primary outcome was percentage excess BMI loss (%EBMIL). Secondary predefined outcomes in both trials included total weight loss, remission of co-morbidities, improvement in quality of life (QoL), and overall morbidity. RESULTS: At baseline, 228 LSG and 229 LRYGB procedures were performed. Five-year follow-up was available for 199 of 228 patients (87.3 per cent) after LSG and 199 of 229 (87.1 per cent) after LRYGB. Model-based mean estimate of %EBMIL was 7.0 (95 per cent c.i. 3.5 to 10.5) percentage points better after LRYGB than after LSG  (62.7 versus 55.5 per cent respectively; P < 0.001). There was no difference in remission of T2DM, obstructive sleep apnoea or QoL improvement; remission for hypertension was better after LRYGB compared with LSG (60.3 versus 44.9 per cent; P = 0.049). The complication rate was higher after LRYGB than LSG (37.2 versus 22.5 per cent; P = 0.001), but there was no difference in mean Comprehensive Complication Index value (30.6 versus 31.0 points; P = 0.859). CONCLUSION: Although LRYGB induced greater weight loss and better amelioration of hypertension than LSG, there was no difference in remission of T2DM, obstructive sleep apnoea, or QoL at 5 years. There were more complications after LRYGB, but the individual burden for patients with complications was similar after both operations.

Functional roles of low calorie sweeteners on gut function.

This short review summarizes the effects of low calorie sweeteners (fructose, non-nutritive low calorie sweeteners) on gut functions focusing on the gut sweet taste receptor system. The effects of these molecules on secretion of gut peptides associated with glycemic homeostasis and appetite regulation is reviewed as well as effects on gastric emptying and glucose absorption.

Gut sweet taste receptors and their role in metabolism.

Obesity is caused by an imbalance between food intake and energy expenditure. In recent decades the gastrointestinal tract has received growing attention as a control parameter for the regulation of appetite and food intake, however regulatory circuits and their interactions are complex. The basic understanding on the role of the gut starts with the notion 'we are what we eat'. Food enters the gastrointestinal tract, which then triggers specific mechanisms or a sensing machinery that respond to specific components of food. Enteroendocrine cells in the small intestine are the anatomical basis for the sensing machinery, which act as neural triggers or as intestinal satiation peptide-secreting cells. These cells express chemosensory receptors that respond to luminal stimuli. The understanding of each gastrointestinal mechanism that might be involved in the process of eating provides a basis for the assessment of the potential of the gastrointestinal tract in the fight against obesity. This review discusses the function of the gut sweet taste receptor T1R2/T1R3 in sensing sweet compounds, as well as its role in gastrointestinal peptide secretion and glucose metabolism.

Effects of chenodeoxycholic acid on the secretion of gut peptides and fibroblast growth factors in healthy humans.

CONTEXT: Recent evidence suggests bile acids (BAs) are involved in the glycemic control via TGR5 activation with the subsequent release of gut peptides and farnesoid X receptor activation with ensuing release of fibroblast growth factors (FGFs). OBJECTIVE: We hypothesized that intraduodenal infusions of chenodeoxycholic acid (CDCA) would stimulate FGF and gut peptide secretion, thereby positively influencing glucose homeostasis. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: This randomized, double-blind, placebo-controlled, crossover trial included 12 healthy volunteers who received intraduodenal infusions (2.0 mL/min for 180 minutes) of saline, CDCA (5 or 15 mmol/L), and a fatty acid (sodium oleate), either alone or with 5 mmol/L CDCA. After 60 minutes, an oral glucose tolerance test (oGTT) was performed. MAIN OUTCOME MEASURES: Plasma levels of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine, cholecystokinin (CCK), total BAs, FGF19, FGF21, C-peptide, insulin, glucose, and glucagon were measured. RESULTS: Within the first 60 minutes, high-concentration CDCA induced a small but significant increase in GLP-1 and CCK secretion (P = .016 and P =.011), whereas plasma C-peptide, insulin, and glucose were not affected. Attenuated C-peptide and insulin release was observed after the oGTT with 15 mmol/L CDCA (P = .013 and P =.011). Plasma BA and FGF19 levels significantly increased after CDCA administration (P = .001 and P < .001). CONCLUSIONS: CDCA modulates GLP-1 and CCK secretion; the effect is small and does not influence glucose levels. The marked increase in plasma BAs and the attenuated insulin release after the oGTT indicate the role of BAs in glycemic control, independent of the incretin axis, and suggest involvement of farnesoid X receptor activation pathways.

The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans.

The recent identification of sweet taste receptors in the gastrointestinal tract has important implications in the control of food intake and glucose homeostasis. Lactisole can inhibit the sweet taste receptor T1R2/T1R3. The objective was to use lactisole as a probe to investigate the physiological role of T1R2/T1R3 by assessing the effect of T1R2/T1R3 blockade on GLP-1, PYY, and CCK release in response to 1) intragastric administration of nutrients or 2) intraduodenal perfusion of nutrients. The study was performed as a randomized, double-blind, placebo-controlled crossover study that included 35 healthy subjects. In part I, subjects received intragastrically 75 g of glucose in 300 ml of water or 500 ml of a mixed liquid meal with or without lactisole. In part II, subjects received an intraduodenal perfusion of glucose (29.3 g glucose/100 ml; rate: 2.5 ml/min for 180 min) or a mixed liquid meal (same rate) with or without lactisole. The results were that 1) lactisole induced a significant reduction in GLP-1 and PYY but not CCK secretion in both the intragastric and the intraduodenal glucose-stimulated parts (P ≤ 0.05), 2) comparison of the inhibitory effect of lactisole showed a significantly greater suppression of the hormone response in the intragastric part (P = 0.023), and 3) lactisole had no effect on liquid meal-stimulated parameters. We conclude that T1R2/T1R3 is involved in glucose-dependent secretion of satiation peptides. However, the results of the liquid meal-stimulated parts show that the receptor alone is not responsible for peptide secretion.

The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).

BACKGROUND & AIMS: Enteroendocrine cells are thought to directly sense nutrients via α-gustducin coupled taste receptors (originally identified in the oral epithelium) to modulate the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). METHODS: We measured mRNA expression of α-gustducin and T1R3 along the human gut; immunohistochemistry was used to confirm co-localization with GLP-1. Functional implication of sweet taste receptors in glucose-stimulated secretion of GLP-1 and PYY was determined by intragastric infusion of glucose with or without lactisole (a sweet taste receptor antagonist) in 16 healthy subjects. RESULTS: α-gustducin was expressed in a region-specific manner (predominantly in the proximal gut and less in ileum and colon, P < 0.05). Both, T1R3 and α-gustducin were co-localized with GLP-1. Glucose-stimulated secretions of GLP-1 (P = 0.026) and PYY (P = 0.034) were reduced by blocking sweet receptors with lactisole. CONCLUSION: Key proteins implicated in taste signaling are present in the human gut and co-localized with GLP-1 suggesting that these proteins are functionally linked to peptide secretion from enteroendocrine cells. Glucose-stimulated secretion of GLP-1 and PYY is reduced by a sweet taste antagonist, suggesting the functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of both peptides in humans.