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Erythritol and xylitol differentially impact brain networks involved in appetite regulation in healthy volunteers.
Meyer-Gerspach, AC, Wingrove, JO, Beglinger, C, Rehfeld, JF, Le Roux, CW, Peterli, R, Dupont, P, O'Daly, O, Van Oudenhove, L, Wölnerhanssen, BK
Nutritional neuroscience. 2022;(11):2344-2358
Abstract
BACKGROUND There is a growing consensus that sugar consumption should be reduced and the naturally occurring, low-calorie sweeteners xylitol and erythritol are gaining popularity as substitutes, but their effect on brain circuitry regulating appetite is unknown. AIM: The study's objective was to examine the effects of the two sweeteners on cerebral blood flow (rCBF) and resting functional connectivity in brain networks involved in appetite regulation, and test whether these effects are related to gut hormone release. METHODS The study was performed as a randomized, double-blind, placebo-controlled, cross-over trial. Twenty volunteers received intragastric (ig) loads of 50g xylitol, 75g erythritol, 75g glucose dissolved in 300mL tap water or 300mL tap water. Resting perfusion and blood oxygenation level-dependent data were acquired to assess rCBF and functional connectivity. Blood samples were collected for determination of CCK, PYY, insulin and glucose. RESULTS We found: (i) xylitol, but not erythritol, increased rCBF in the hypothalamus, whereas glucose had the opposite effect; (ii) graph analysis of resting functional connectivity revealed a complex pattern of similarities and differences in brain network properties following xylitol, erythritol, and glucose; (iii) erythritol and xylitol induced a rise in CCK and PYY, (iv) erythritol had no and xylitol only minimal effects on glucose and insulin. CONCLUSION Xylitol and erythritol have a unique combination of properties: no calories, virtually no effect on glucose and insulin while promoting the release of gut hormones, and impacting appetite-regulating neurocircuitry consisting of both similarities and differences with glucose.
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Management of gallstone disease prior to and after metabolic surgery: a single-center observational study.
Dirnberger, AS, Schneider, R, Slawik, M, Linke, K, Kraljević, M, Wölnerhanssen, B, Peterli, R
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2022;(2):182-188
Abstract
BACKGROUND Rapid weight loss after bariatric surgery is a risk factor for gallstone formation. There are different strategies regarding its management in bariatric patients, including prophylactic cholecystectomy (CCE) in all patients, concomitant CCE only in symptomatic patients, or concomitant CCE in all patients with known gallstones. We present the safety and long-term results of the last concept. METHOD Retrospective single-center analysis of a prospective database on perioperative and long-term results of patients with laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) over a 15-year period. The minimal follow-up was 24 months. Concomitant CCE was intended for all patients with gallstones detected by preoperative sonography. SETTING Academic teaching hospital in Switzerland. RESULTS After exclusion of patients with a history of CCE (11.5%), a total of 1174 patients (69.6% LRYGB, 30.4% LSG) were included in the final analysis. Preoperative gallbladder pathology was detected in 21.2% of patients, of whom 98.4%, or 20.9% of the total patients, received a concomitant CCE. The additional procedure prolonged the average operation time by 38 minutes (not significant) and did not increase the complication rate compared with bariatric procedure without CCE (3.7% versus 5.7%, P = .26). No complication was directly linked to the CCE. Postoperative symptomatic gallbladder disease was observed in 9.3% of patients (LRYGB 7.0% versus LSG 2.3%, P = .15), with 19.8% of those patients initially presenting with a complication. CONCLUSION The concept of concomitant CCE in primary bariatric patients with gallstones was feasible and safe. Nevertheless, 9.3% of primary gallstone-free patients developed postoperative symptomatic gallbladder disease and required subsequent CCE despite routine ursodeoxycholic acid prophylaxis.
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Does the non-absorbable suture closure of the jejunal mesenteric defect reduce the incidence and severity of internal hernias after laparoscopic Roux-en-Y gastric bypass?
Schneider, R, Schulenburg, M, Kraljević, M, Klasen, JM, Peters, T, Wölnerhanssen, B, Peterli, R
Langenbeck's archives of surgery. 2021;(6):1831-1838
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Abstract
PURPOSE Internal hernias (IH) are frequent complications after laparoscopic Roux-en-Y gastric bypass (LRYGB). Closure of the jejunal mesenteric and the Petersen defect reduces IH incidence in prospective and retrospective trials. This study investigates whether closing the jejunal mesenteric space alone by non-absorbable suture and splitting the omentum can be beneficial to prevent IH after LRYGB. METHODS Observational cohort study of 785 patients undergoing linear LRYGB including omental split at a single institution, with 493 patients without jejunal mesenteric defect closure and 292 patients with closure by non-absorbable suture, and a minimal follow-up of 2 years. Patients were assessed for appearance and severity of IH. Additionally, open mesenteric gaps without herniated bowel as well as early obstructions due to kinking of the entero-enterostomy (EE) were explored. RESULTS Through primary mesenteric defect closure, the rate of manifest jejunal mesenteric and Petersen IH could be reduced from 6.5 to 3.8%, but without reaching statistical significance. The most common location for an IH was the jejunal mesenteric space, where defect closure during primary surgery reduced the rate of IH from 5.3 to 2.4%. Higher weight loss seemed to increase the risk of developing an IH. CONCLUSION The closure of the jejunal mesenteric defect by non-absorbable suture may reduce the rate of IH at the jejunal mesenteric space after LRYGB. However, the beneficial effect in our collective is smaller than expected, particularly in patients with good weight loss. The Petersen IH rate remained low by consequent T-shape split of the omentum without suturing of the defect.
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Different limb lengths in gastric bypass surgery: study protocol for a Swiss multicenter randomized controlled trial (SLIM).
Kraljević, M, Schneider, R, Wölnerhanssen, B, Bueter, M, Delko, T, Peterli, R
Trials. 2021;(1):352
Abstract
BACKGROUND Obesity and type 2 diabetes mellitus are reaching epidemic proportions. In morbidly obese patients, bariatric operations lead to sustained weight loss and relief of comorbidities in the majority of patients. Laparoscopic Roux-Y-gastric bypass (RYGB) is one of the most frequently performed operations, but it is still unknown why some patients respond better than others. Therefore, a number of variations of this operation have been introduced. Recent evidence suggests that a longer bypassed biliopancreatic limb (BPL) has the potential to be more effective compared to the standard RYGB with a shorter BPL length. This article describes the design and protocol of a randomized controlled trial comparing the outcome of a RYGB operation with a long versus short BPL. METHODS/DESIGN The trial is designed as a multicenter, randomized, patient- and observer-blinded trial. The relevant ethics committee has approved the trial protocol. To demonstrate that long BPL RYGB is superior compared to short BPL RYGB in terms of weight loss and resolution of T2DM, the study is conducted as a superiority trial. Postoperative percent total weight loss and nutritional deficiency rate are the primary endpoints, whereas morbidity, mortality, remission of obesity-related comorbidities and quality of life are secondary endpoints. Eight hundred patients, between 18 and 65 years and with a body mass index (BMI) from 35 to 60 kg/m2 who meet the regulatory rules for bariatric surgery in Switzerland, will be randomized. The endpoints and baseline measurements will be assessed pre-, intra-, and postoperatively. DISCUSSION With its high number of patients and a 5-year follow-up, this study will answer questions about effectiveness and safety of long BPL RYGB and provide level I evidence for improvement of the standard RYGB. These findings might therefore potentially influence global bariatric surgery guidelines. TRIAL REGISTRATION ClinicalTrials.gov NCT04219787 . Registered on 7 January 2020.
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Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.
Wölnerhanssen, BK, Drewe, J, Verbeure, W, le Roux, CW, Dellatorre-Teixeira, L, Rehfeld, JF, Holst, JJ, Hartmann, B, Tack, J, Peterli, R, et al
Diabetes, obesity & metabolism. 2021;23(6):1311-1321
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Plain language summary
In recent years, erythritol, a non-calorie sweetener, has gained popularity due to the rise in obesity and Type 2 diabetes worldwide. The purpose of this randomised, placebo-controlled, double-blind, cross-over trial was to assess the effects of erythritol on the release of gut hormones, speed of gastric emptying, and the release of glucagon, motilin, and glucose-dependent insulinotropic polypeptide after erythritol administration. Erythritol in doses of ten, twenty-five, and fifty grams was well tolerated by the participants. The administration of erythritol induced a statistically significant dose-dependent stimulation of gut hormones such as plasma cholecystokinin, active glucagon‐like peptide‐1 and peptide tyrosine. Compared to the placebo, participants had slower gastric emptying with erythritol. Erythritol had no effect on the levels of motilin, glucose-dependent insulinotropic polypeptide, blood glucose, insulin, glucagon, blood lipids, or uric acid. Erythritol should be evaluated in larger, robust studies to determine whether it improves glycaemic control. However, healthcare professionals can use the results of this study to understand the potential uses of erythritol in the management of obesity and type 2 diabetes.
Abstract
AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.
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Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study.
Meyer-Gerspach, AC, Drewe, J, Verbeure, W, Roux, CWL, Dellatorre-Teixeira, L, Rehfeld, JF, Holst, JJ, Hartmann, B, Tack, J, Peterli, R, et al
Nutrients. 2021;(1)
Abstract
Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.
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Outcome of revisional bariatric surgery for insufficient weight loss after laparoscopic Roux-en-Y gastric bypass: an observational study.
Linke, K, Schneider, R, Gebhart, M, Ngo, T, Slawik, M, Peters, T, Peterli, R
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2020;(8):1052-1059
Abstract
BACKGROUND Insufficient weight loss or secondary weight regain with or without recurrence of comorbidity can occur years after laparoscopic Roux en Y gastric bypass (LRYGB). In selected patients, increasing restriction or adding malabsorption may be a surgical option after conservative measures failed. OBJECTIVES Evaluation of short and long term results of revisional surgery for insufficient weight loss or weight regain after LRYGB. SETTING Tertiary hospital. METHODS Retrospective analysis of prospectively collected data from a cohort of 1150 LRYGB patients. Included were patients, who underwent revisional bariatric surgery after LRYGB for insufficient weight loss with a follow-up of minimal 1 year. RESULTS Fifty-four patients were included in the analysis. After an interdisciplinary evaluation, patients with insufficient weight loss, signs of dumping syndrome, and lacking restriction were offered a nonadjustable band around the pouch (banded group, n = 34) and patients with sufficient restriction, excellent compliance, and adherence were offered a revision to laparoscopic biliopancreatic diversion (BPD group, n = 20). The revisional procedure was performed 3.3 ± 2.3 years after LRYGB in the banded-group and after 6.4 ± 4.3 years in the BPD group (P = .001). Mean body mass index at the time of the primary bariatric procedure was 41.7 ± 6.2 kg/m2 in the banded group and 45.2 ± 8.2 kg/m2 in the BPD group (P = .08); minimal body mass index between both operations was 29.1 ± 4.7 kg/m2 in the banded group and 36.5 ± 9.4 kg/m2 in the BPD group, and, at the time of revisional surgery, 31.4 ± 5.5 kg/m2 in the banded group and 40.8 ± 6.7 kg/m2 in the BPD group (P = .0001). The mean body mass index difference 1 year after revisional surgery was 1.3 ± 3.0 kg/m2 in the banded group and 6.7 ± 4.5 kg/m2 in the BPD group (P = .01). In the banded group, 11 patients (32.4%) needed removal of the band, 4 patients (11.8%) needed an adjustment, and 4 patients (11.8%) were later converted to BPD. In the BPD group, 2 (10.0%) patients needed revision for severe protein malabsorption. CONCLUSIONS Insufficient weight loss or secondary weight regain after LRYGB is a rare indication for revisional surgery. Banded bypass has modest results for additional weight loss but can help patients suffering from dumping. In very carefully selected cases, BPD can achieve additional weight loss with acceptable complication rate but higher risk for reoperation. Future "adjuvant medical treatments," such as glucagon-like peptide 1 analogues and other pharmacologic treatment options could be an alternative for achieving additional weight loss and better metabolic response.
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First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy.
Nussbaumer, R, Meyer-Gerspach, AC, Peterli, R, Peters, T, Beglinger, C, Chiappetta, S, Drewe, J, Wölnerhanssen, B
Obesity facts. 2020;(6):584-595
Abstract
BACKGROUND Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. OBJECTIVE To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. SETTING University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. METHODS Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. RESULTS Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0-60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0-10 min), second-phase insulin secretion (AUC 10-60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. CONCLUSION Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.
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Comparison of metabolic outcomes in patients undergoing laparoscopic roux-en-Y gastric bypass versus sleeve gastrectomy - a systematic review and meta-analysis of randomised controlled trials.
Hayoz, C, Hermann, T, Raptis, DA, Brönnimann, A, Peterli, R, Zuber, M
Swiss medical weekly. 2018;:w14633
Abstract
BACKGROUND AND OBJECTIVES Bariatric surgery is the most effective treatment for morbid obesity and is known to have beneficial effects on glycaemic control in patients with type 2 diabetes mellitus (T2DM) and in diabetes prevention. The preferred type of surgery and mechanism of action is, however, unclear. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of laparoscopic roux-en-Y gastric bypass (RYGB) with those of sleeve gastrectomy (SG) on metabolic outcome, with a special focus on glycaemic control. METHODS A literature search of the Medline, Pubmed, Cochrane, Embase and SCOPUS databases was performed in November 2014 for RCTs comparing RYGB with SG in overweight and obese patients with or without T2DM. The primary outcome was improvement in postoperative glycaemic control. Secondary outcomes included weight-related and lipid metabolism parameters. Synthesis of these data followed established statistical procedures for meta-analysis. RESULTS Sixteen RCTs with a total of 1132 patients with overweight or obesity were included in the analysis. When compared with patients who underwent SG, those who underwent RYGB showed no difference after 12 months in mean fasting blood glucose (mean difference [MD] -6.22 mg/dl, 95% confidence interval [CI] -17.27 to 4.83; p <0.001). However, there was a better outcome with RYGB, with lower mean fasting glucose levels at 24 months (MD -16.92 mg/dl, 95% CI -21.67 to -12.18), 36 months (MD -5.97mg/dl, 95% CI -9.32 to -2.62) and at 52 months (MD -15.20 mg/dl, 95% CI -27.35 to -3.05) mg/dl; p = 0.010) and lower mean glycated haemoglobin (HbA1 at 12 months (MD -0.47%, 95% CI -0.73 to -0.20%; p <0.001) and at 36 months postoperatively compared to SG. Fasting insulin levels and HOMA indices showed no difference at any stage of follow-up. In the subgroup including only diabetic patients HbA1c showed lower levels at 12 months (MD -0.46%, 95% CI-0.73 to -0.20%). No difference was found for the fasting insulin at baseline and after 12 months. Similarly, when compared to SG, patients that underwent RYGB had lower low-density lipoproteins at 12 months. This effect was lost at 36 months. Patients undergoing RYGB also had lower triglycerides at 12 months and at 52 months, lower cholesterol at 60 months and an improvement of BMI at 52 months postoperatively. BMI values at 12 months and low-density lipoprotein levels at 12 and 36 months were lower for diabetic patients only, as in the overall analysis. CONCLUSION Based on this meta-analysis, RYGB is more effective than SG in improving weight loss and short- and mid-term glycaemic and lipid metabolism control in patients with and without T2DM. Therefore, unless contraindicated, RYGB should be the first choice to treat patients with obesity and T2DM and/or dyslipidaemia.
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Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects.
Wölnerhanssen, BK, Cajacob, L, Keller, N, Doody, A, Rehfeld, JF, Drewe, J, Peterli, R, Beglinger, C, Meyer-Gerspach, AC
American journal of physiology. Endocrinology and metabolism. 2016;(11):E1053-61
Abstract
With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol have been known for a long time and their beneficial effects on caries prevention and potential health benefits in diabetic patients have been demonstrated in several studies. Glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are released from the gut in response to food intake, promote satiation, reduce gastric emptying (GE), and modulate glucose homeostasis. Although glucose ingestion stimulates sweet taste receptors in the gut and leads to incretin and gastrointestinal hormone release, the effects of xylitol and erythritol have not been well studied. Ten lean and 10 obese volunteers were given 75 g of glucose, 50 g of xylitol, or 75 g of erythritol in 300 ml of water or placebo (water) by a nasogastric tube. We examined plasma glucose, insulin, active GLP-1, CCK, and GE with a [(13)C]sodium acetate breath test and assessed subjective feelings of satiation. Xylitol and erythritol led to a marked increase in CCK and GLP-1, whereas insulin and plasma glucose were not (erythritol) or only slightly (xylitol) affected. Both xylitol and erythritol induced a significant retardation in GE. Subjective feelings of appetite were not significantly different after carbohydrate intake compared with placebo. In conclusion, acute ingestion of erythritol and xylitol stimulates gut hormone release and slows down gastric emptying, whereas there is no or only little effect on insulin release.