Comment on: Effect of laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy on fasting gastrointestinal and pancreatic peptide hormones: A prospective nonrandomized trial

Abstract

Over the past few years, a number of papers have tried to decipher the hormonal mechanisms that may promote weight loss after bariatric surgery in parallel or in conjunction with pure restrictive aspects of any modern bariatric procedure. Particular attention was paid to type 2 diabetes as, since a publication by Walter Pories [ [1] Pories WJ Swanson S MacDonald KG et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995; 222: 339-350 Crossref PubMed Scopus (1892) Google Scholar ], there was an improvement in glucose metabolism that by far preceded the magnitude of weight loss after gastric bypass surgery. Several recent reviews [ 2 Holst JJ Madsbad S Bojsen-Moller KN et al. Mechanisms in bariatric surgery: gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis. 2018; 14: 708-714 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar , 3 Meek CL Lewis HB Reimann F Gribble FM Park AJ The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016; 77: 28-37 Crossref PubMed Scopus (173) Google Scholar , 4 Steinert RE Feinle-Bisset C Asarian L Horowitz M Beglinger C Geary N Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev. 2017; 97: 411-463 Crossref PubMed Scopus (331) Google Scholar ] have discussed the role of the various gut hormones in bariatric and metabolic surgery, but the present study by Yang et al. represents one of the very few original studies comparing the 2 most frequently performed bariatric procedures: gastric bypass (RYGB) and sleeve gastrectomy (SG) [ 5 Nannipieri M Baldi S Mari A et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab. 2013; 98: 4391-4399 Crossref PubMed Scopus (200) Google Scholar , 6 Ramón JM Salvans S Crous X et al. Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut hormones: a prospective randomised trial. J Gastrointest Surg. 2012; 16: 1116-1122 Crossref PubMed Scopus (136) Google Scholar , 7 Syu YF Inui A Chen CY A perspective on metabolic surgery from a gastroenterologist. J Pharmacol Sci. 2017; 133: 61-64 Crossref PubMed Scopus (7) Google Scholar ]. Among the different gut hormones studied, there is a relative consensus [ 5 Nannipieri M Baldi S Mari A et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab. 2013; 98: 4391-4399 Crossref PubMed Scopus (200) Google Scholar , 6 Ramón JM Salvans S Crous X et al. Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut hormones: a prospective randomised trial. J Gastrointest Surg. 2012; 16: 1116-1122 Crossref PubMed Scopus (136) Google Scholar , 7 Syu YF Inui A Chen CY A perspective on metabolic surgery from a gastroenterologist. J Pharmacol Sci. 2017; 133: 61-64 Crossref PubMed Scopus (7) Google Scholar , 8 De Silva A BloomSR Gut hormones and appetite control: a focus on PYY and GLP-1 as therapeutic targets in obesity. Gut Liver. 2012; 6: 10-20 Crossref PubMed Scopus (208) Google Scholar , 9 Dimitriadis E Daskalakis M Kampa M Peppe A Papadakis JA Melissas J Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study. Ann Surg. 2013; 257: 647-654 Crossref PubMed Scopus (102) Google Scholar ] that both SG and RYGB increase the 1-year fasting levels of the 2 anorectic incretins glucagon-like-peptide 1 (GLP1) and peptide YY (PYY) compared with preoperative baseline, as confirmed by the present report. However, there are some discrepancies regarding GLP1. Farey [ [10] Farey JE Preda TC Fisher OM et al. Effect of laparoscopic sleeve gastrectomy on fasting gastrointestinal, pancreatic, and adipose-derived hormones and on non-esterified fatty acids. Obes Surg. 2017; 27: 399-407 Crossref PubMed Scopus (22) Google Scholar ] found a significant decrease 3 months after SG, and 2 reviews of the literature reported no significant change in concentration when analyzing published data on SG and RYGB [ 2 Holst JJ Madsbad S Bojsen-Moller KN et al. Mechanisms in bariatric surgery: gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis. 2018; 14: 708-714 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar , 3 Meek CL Lewis HB Reimann F Gribble FM Park AJ The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016; 77: 28-37 Crossref PubMed Scopus (173) Google Scholar ]. Although GLP1 and PYY are both produced by L cells in the ileum and colon, it has been established [ [8] De Silva A BloomSR Gut hormones and appetite control: a focus on PYY and GLP-1 as therapeutic targets in obesity. Gut Liver. 2012; 6: 10-20 Crossref PubMed Scopus (208) Google Scholar ] that the hormones were released within minutes of food intake in nonobese, nonoperated individuals, peaked even before the nutrients entered the distal gut, and remained elevated up to 6 hours. In addition, as these hormones decrease gastric emptying, it is difficult to support the sole theory of early delivery of food into the distal intestine to trigger GLP1 and PYY secretion, especially in the case of SG, for which studies report either accelerated or slowed gastric emptying. This is consistent with elevated GLP1 levels even after gastric banding. Therefore, another triggering mechanism should be involved. A consensus also exists regarding the gastric inhibitory peptide, which rapidly returns to baseline levels after SG and RYGB, although there is only 1 study on SG [ 2 Holst JJ Madsbad S Bojsen-Moller KN et al. Mechanisms in bariatric surgery: gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis. 2018; 14: 708-714 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar , 3 Meek CL Lewis HB Reimann F Gribble FM Park AJ The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016; 77: 28-37 Crossref PubMed Scopus (173) Google Scholar , 10 Farey JE Preda TC Fisher OM et al. Effect of laparoscopic sleeve gastrectomy on fasting gastrointestinal, pancreatic, and adipose-derived hormones and on non-esterified fatty acids. Obes Surg. 2017; 27: 399-407 Crossref PubMed Scopus (22) Google Scholar ]. Although the present study confirms the general decrease in gastric inhibitory peptide concentrations, especially after RYGB due to the exclusion of the duodenum and part of the jejunum, where this satiety hormone is produced, it is difficult to establish a major direct role in promoting weight loss and diabetes remission. Ghrelin has long been implicated in the weight control process after bariatric surgery because it is produced by the gastric fundus, and it seemed logical that removing or excluding this part of the stomach would lead to a postoperative decrease. If a significant postprandial and fasting decrease from baseline is observed after SG in the published papers, including this one [ 3 Meek CL Lewis HB Reimann F Gribble FM Park AJ The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016; 77: 28-37 Crossref PubMed Scopus (173) Google Scholar , 5 Nannipieri M Baldi S Mari A et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J Clin Endocrinol Metab. 2013; 98: 4391-4399 Crossref PubMed Scopus (200) Google Scholar , 6 Ramón JM Salvans S Crous X et al. Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut hormones: a prospective randomised trial. J Gastrointest Surg. 2012; 16: 1116-1122 Crossref PubMed Scopus (136) Google Scholar , 7 Syu YF Inui A Chen CY A perspective on metabolic surgery from a gastroenterologist. J Pharmacol Sci. 2017; 133: 61-64 Crossref PubMed Scopus (7) Google Scholar , 9 Dimitriadis E Daskalakis M Kampa M Peppe A Papadakis JA Melissas J Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study. Ann Surg. 2013; 257: 647-654 Crossref PubMed Scopus (102) Google Scholar , 10 Farey JE Preda TC Fisher OM et al. Effect of laparoscopic sleeve gastrectomy on fasting gastrointestinal, pancreatic, and adipose-derived hormones and on non-esterified fatty acids. Obes Surg. 2017; 27: 399-407 Crossref PubMed Scopus (22) Google Scholar ], the situation is less clear after RYGB. Except for a review [ [2] Holst JJ Madsbad S Bojsen-Moller KN et al. Mechanisms in bariatric surgery: gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis. 2018; 14: 708-714 Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar ] and a study where it remains significantly decreased although in a lesser extent compared with SG [ [4] Steinert RE Feinle-Bisset C Asarian L Horowitz M Beglinger C Geary N Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev. 2017; 97: 411-463 Crossref PubMed Scopus (331) Google Scholar ], ghrelin, whether in the fasting or postprandial phase, remains either unchanged or even decreased at 1 year postoperatively after RYGB [ [6] Ramón JM Salvans S Crous X et al. Effect of Roux-en-Y gastric bypass vs sleeve gastrectomy on glucose and gut hormones: a prospective randomised trial. J Gastrointest Surg. 2012; 16: 1116-1122 Crossref PubMed Scopus (136) Google Scholar ]. It should even be increased, logically, in response to weight loss in its quality of “hunger hormone” [ [7] Syu YF Inui A Chen CY A perspective on metabolic surgery from a gastroenterologist. J Pharmacol Sci. 2017; 133: 61-64 Crossref PubMed Scopus (7) Google Scholar ]. Oddly enough, this hormone was found at a lower concentration in obese individuals prior to SG compared with nonobese controls [ [10] Farey JE Preda TC Fisher OM et al. Effect of laparoscopic sleeve gastrectomy on fasting gastrointestinal, pancreatic, and adipose-derived hormones and on non-esterified fatty acids. Obes Surg. 2017; 27: 399-407 Crossref PubMed Scopus (22) Google Scholar ]. Interaction between the different incretins is still very much unknown, but intravenous infusion of cholecystokininor PYY in humans induced a decrease in ghrelin levels, while GLP1 infusion did not result in any change [ [4] Steinert RE Feinle-Bisset C Asarian L Horowitz M Beglinger C Geary N Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev. 2017; 97: 411-463 Crossref PubMed Scopus (331) Google Scholar ]. This may explain the changes after RYGB despite the lack of fundus resection. Ghrelin, GLP1, PYY, and cholecystokinin, which were not studied in the present paper, are nonetheless implicated in negative-feedback loops in relation to their role on digestive motility and sensing [ [4] Steinert RE Feinle-Bisset C Asarian L Horowitz M Beglinger C Geary N Ghrelin, CCK, GLP-1, and PYY(3-36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev. 2017; 97: 411-463 Crossref PubMed Scopus (331) Google Scholar ]. Exclusion of the duodenum and part of the jejunum can only explain why gastric inhibitory peptide levels are still significantly decreased from baseline 1 year after RYGB in the present study, whereas the few papers that measured this incretin found little change notably after SG with a possible influence on diabetic patients [ 3 Meek CL Lewis HB Reimann F Gribble FM Park AJ The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones. Peptides. 2016; 77: 28-37 Crossref PubMed Scopus (173) Google Scholar , 10 Farey JE Preda TC Fisher OM et al. Effect of laparoscopic sleeve gastrectomy on fasting gastrointestinal, pancreatic, and adipose-derived hormones and on non-esterified fatty acids. Obes Surg. 2017; 27: 399-407 Crossref PubMed Scopus (22) Google Scholar ]. The exact mechanisms through which incretins may take part in weight loss as well as diabetes improvement are still unclear. So far, whether after SG or RYGB, GLP1 and PYY appear to be the most involved incretins and responsible at least in part for the improvement in insulin sensitivity. The dramatic changes in volume and quality of food intake after these surgeries could explain a centrally mediated increase in serum levels. However, all the studies include very small populations rarely exceeding 10 patients, usually with a proportion having type 2 diabetes. Whether they act as promoters or consequences of the weight loss is unclear, but they appear as significantly altered in patients with better weight loss results (excess body mass index lost >60%) [ [11] Dirksen C Jorgenson NB Bodsen-Moller KN et al. Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass. Int J Obes (Lond). 2013; 37: 1452-1459 Crossref PubMed Scopus (174) Google Scholar ]. Studies with a longer follow-up comparing weight loss results as well as diabetic and nondiabetic patients might be necessary.