BACKGROUND:Obesity prevalence is rising globally and is associated with multiple comorbidities. While metabolic bariatric surgery (MBS) is effective for weight loss and comorbidity improvement, the influence of obesity onset and duration on postoperative outcomes remains unclear. OBJECTIVES:To evaluate whether age at obesity onset and obesity duration affect weight loss, comorbidity improvement, and postoperative complications following MBS. SETTING:Three University Hospitals, DACH-region (Germany, Austria, Switzerland). METHODS:Data from 1855 adults undergoing primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2010 and 2023 were retrospectively analyzed. Obesity onset was categorized as childhood (<10 years), puberty (10-17 years), or adult (≥18 years). Postoperative outcomes were assessed using % total body weight loss (%TBWL) and the SF-Bari Score, incorporating weight loss, comorbidity remission, and complications, over 4 years. Multivariable linear and mixed-effects models adjusted for age, sex, procedure type, and obesity duration. RESULTS:Baseline body mass index was highest in childhood-onset obesity (49.1 ± 9.2 kg/m2) versus adult-onset (46.6 ± 7.8 kg/m2, P < .005). Peak %TBWL at 2 years was 31.1% (childhood), 30.4% (puberty), 29.3% (adult), converging by year 4 (29.0%, 27.8%, 26.6%; P = .042). SF-Bari Scores were consistently "Good" (104-110). Age at surgery and procedure type were the strongest predictors: each additional year of age at surgery reduced %TBWL by .21%, and SG led to 3.8% less %TBWL than RYGB (P < .001). Obesity duration was not independently associated with weight loss. CONCLUSIONS:Childhood-onset obesity is linked to higher baseline BMI and parental obesity but does not impair mid-term MBS outcomes. Age at surgery and procedure type are primary determinants of postoperative weight loss, supporting equitable surgical access across obesity-onset groups.

BACKGROUND:Predicting postoperative body mass index (BMI) trajectories and long-term type 2 diabetes (T2D) remission after bariatric surgery remains challenging. Existing models often rely on baseline variables only and fail to incorporate dynamic postoperative changes. This study aimed to develop and validate a multicentre machine-learning framework that predicts individualized BMI trajectories and T2D remission using routinely available preoperative data and time-dependent weight evolution. METHODS:This multicentre retrospective cohort study included adult patients who underwent Roux-en-Y gastric bypass or sleeve gastrectomy across 11 European centres (2012-2023). Variables with > 30% missing data were excluded; remaining missing values were imputed iteratively. A two-stage approach was used: a regression model predicting postoperative BMI at 3-60 months using an autoregressive design; and a classification model predicting T2D remission using baseline features and predicted BMI trajectories. Internal performance was evaluated with ten-fold and leave-one-clinic-out cross-validation; external validation used an independent cohort from Linköping, Sweden. RESULTS:Of the 11 457 patients initially identified, 9652 patients with complete baseline and follow-up information were used for the analysis. The best BMI model (HistGradientBoosting) achieved a root mean square error (RMSE) of 1.11 kg/m2 (95% confidence interval 1.07 to 1.14) and a mean absolute error (MAE) of 0.62 kg/m2 across clinics; external testing showed an RMSE of 1.12 kg/m2 (95% confidence interval 1.11 to 1.12) and an MAE of 0.63 kg/m2. The T2D remission classifier (XGBoost) obtained a Macro F1 score of 0.88 (precision 0.87, recall 0.88), with an external F1 score of 0.89. Incorporating predicted BMI trajectories improved discrimination compared with baseline-only models (C-index 0.95 versus 0.93). CONCLUSION:A two-stage machine-learning framework has high predictive performance for postoperative BMI and T2D remission up to 5 years after bariatric surgery. Dynamic incorporation of predicted weight trajectories enhances metabolic risk prediction and supports individualized counselling and postoperative management.

Roux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes (T2D), but the physiological mechanisms underlying sustained improvements in glycemic control remain incompletely understood. To descriptively compare short- and long-term changes in glycemic control and insulin secretion dynamics following RYGB or best medical care (BMC) using an intravenous glucagon stimulation test (GST) in patients with non-severe obesity (BMI <35 kg/m2) and insulin-treated T2D. Thirty-five patients with long-standing insulin-dependent T2D were enrolled from two prospective studies and received either BMC or RYGB. GST was performed at baseline and repeated after 3, 6, 12 and 24 months. Changes in glucose, insulin, and C-peptide responses were analyzed. Exploratory indices derived from the GST were used to assess longitudinal within-subject changes. Diabetes remission occurred in 10

AIMS:Type 2 diabetes (T2D) is characterized by its clinical heterogeneity. Newly described T2D subphenotypes, each with distinct metabolic and co-morbidity risk profiles, may enable a more personalized care. This study examined whether these subphenotypes can predict outcomes in patients undergoing metabolic and bariatric surgery (MBS). MATERIALS AND METHODS:A total of 233 people with T2D from four clinical centres undergoing MBS were retrospectively assigned to T2D subphenotypes based on the Ahlqvist methodology. The primary outcome was T2D remission at 2 years; secondary outcomes included changes in HOMA2-%B, HOMA2-IR, and total body weight loss (%TWL). Intraoperative liver biopsies were evaluated for metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). RESULTS:All participants were classified as mild obesity-related diabetes (MOD) (62.2%), severe insulin-resistant diabetes (SIRD) (19.7%), or SIDD (18.1%). At 2 years, diabetes remission was lower in severe insulin-deficient diabetes (SIDD) (36.7%) than MOD (79.3%) and SIRD (97.2%; p < 0.001). SIDD had lower BMI (38.3 vs. 45.2 and 43.2 kg/m2; p < 0.001) and worse beta-cell function (HOMA2-%B, 92.4 vs. 131.5 vs. 164; p = 0.010), with highest HOMA2-IR in SIRD (6.0 ± 3.4 vs. 4.4 ± 2.8 vs. 3.6 ± 1.9; p < 0.001). %TWL was similar across subphenotypes. SIDD showed higher baseline MASH prevalence (60.5% vs. 46.3% vs. 46.3%). CONCLUSION:T2D subphenotypes respond differently to T2D remission after MBS with SIDD showing a significantly lower remission rate than MOD and SIRD at 2 years. Considering metabolic status in treatment decisions may improve patient outcomes.

The sugar alcohol erythritol occurs naturally in fruits and fermented foods, is used as a sweetener, and is also endogenously synthesized via the pentose-phosphate pathway and metabolized into erythronate. Untargeted metabolomic studies have associated elevated plasma erythritol and erythronate concentrations with metabolic disorders, while weight loss has been linked to decreased plasma erythritol concentrations. In this trial, two complementary analyses were performed to identify predictors of fasting erythritol and erythronate concentrations across different populations and to assess changes in these metabolites following bariatric surgery-induced weight loss. Fasting plasma samples from 30 lean adolescents, 50 lean adults, and 138 adults with obesity (including 15 who had undergone bariatric surgery) were analyzed to measure erythritol, erythronate, glucose, and insulin concentrations. Across all populations, age but not body mass index (BMI), glucose, or insulin, was a significant predictor of fasting erythritol concentrations. Fasting erythronate concentrations were associated with both age and BMI. Post-surgery, change in BMI but not fasting glucose or insulin was a predictor of changes in fasting erythritol concentrations, while time was the only predictor of changes in fasting erythronate concentrations. Although the metabolic processes regulating the endogenous erythritol and erythronate production remain unclear, our findings suggest that age-related physiological changes may influence fasting concentrations of both erythritol and erythronate.

BACKGROUND:The Swiss-Finnish Bariatric Metabolic Outcome Score (SF-BARI Score), based on merged data of two RCTs, is a composite endpoint designed to evaluate and categorize outcomes after metabolic bariatric surgery (MBS). The aim of this study was to externally validate the score using registry data. METHODS:Individual patient data were included from the Dutch Audit for Treatment of Obesity, the Scandinavian Obesity Surgery Registries (SOReg-Sweden and SOReg-Norway), and the merged RCT data used for establishing the SF-BARI Score. All patients undergoing primary MBS from January 2010 to June 2018, with complete baseline characteristics, as well as complete 1- and 5-year follow-up data, were included. The mean total score and distribution were compared between the combined registry and merged RCT data. RESULTS:There was no statistically significant difference in the mean SF-BARI Score between the registries (21 603 patients) and merged RCTs (457 patients) at 5 years (90.9 versus 89.1 points; difference = 1.8 (95% c.i. -1.0 to 4.7); P = 0.212), and the score distribution was similar. Statistically significant differences in baseline characteristics existed regarding sex (male 20.9% versus 29.3%), type 2 diabetes (16.7% versus 33.9%), hypertension (30.4% versus 66.1%), dyslipidaemia (13.7% versus 46.5%), obstructive sleep apnoea syndrome (12.0% versus 17.4%), and sleeve gastrectomy (SG) rate (21.0% versus 49.9%) (P < 0.001). The mean score estimate at 5 years in Roux-en-Y gastric bypass was 11.2 (95% c.i. 10.2 to 12.2) points higher compared with SG (P < 0.001). CONCLUSION:This study verified the feasibility of the SF-BARI Score, enabling standardized reporting and allowing for comparison of different treatment modalities.

Background: Bariatric and metabolic surgery tourism (BMT) is becoming an increasingly popular route to treatment for patients living with obesity. Recent reports have highlighted that some patients travelling abroad for bariatric surgery have received inadequate care, fraudulent care, and, tragically, some cases have resulted in death. This study aimed to define consensus in Europe regarding safe practices concerning BMT. Materials and methods: IFSO-EC, EASO and ECPO initiated a task force to delineate safe practices in BMT. Two expert European panels were convened, one comprised of healthcare professionals (identified from EASO and IFSO-EC) and the other of patient representatives (identified from ECPO). The study utilized a modified Delphi consensus methodology, and 135 questions were administered. Surveys were conducted anonymously online, and consensus was defined as 70% agreement. Themes analyzed regarding BMT included regulation, pre-operative evaluation, operative care, post-operative care, advertising and online information. Results: One hundred and nineteen healthcare professionals and 88 patient representatives participated from 26 countries. The healthcare professional panel included 66 bariatric surgeons, 28 endocrinologists, 18 dietitians, three nurses, two psychologists, one general practitioner and one gastroenterologist. Three questionnaire rounds were conducted for the healthcare professional panel, and two were performed for the patient representative panel. Consensus recommendations were given across all themes relevant to BMT. These included evaluating and managing psychological health, sleep apnea, cardiovascular disease, liver health and dietetic assessment. The recommendations covered the requirements for regulatory standards, including surgeon accreditation and procedural volume. They also included recommendations regarding patient education, standardized operative care, online information provision, and follow-up. Conclusions: Through collaboration with healthcare professionals and patients living with obesity, we provide European recommendations regarding safe practices concerning BMT. Further evaluation is required regarding outcomes following BMT. These data, alongside the Delphi consensus recommendations, will inform BMT clinical guideline development.

Postoperative outcomes after metabolic and bariatric (MBS) can vary due to preoperative behaviors and psychological factors, with several eating patterns (EPs), including eating disorders (EDs), often associated with suboptimal weight loss. Some guidelines even consider EDs a contraindication for MBS. This study examined the impact of EPs on long-term outcomes after MBS. A retrospective analysis was conducted on prospectively collected data from 1550 patients who underwent primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2010 and 2018. Patients were categorized based on preoperative EPs, including binge eating disorder (BED), snacking behavior (SB), sweet eating habit (SEH), fat eating habit (FEH), night eating syndrome (NES), excessive eating habit (EEH), or no present EP. Demographics, morbidity, weight loss, comorbidities, and complications were assessed over 5 years. Outcomes were measured using the SF-BARI score. EPs were common (67.6%), with many patients exhibiting multiple patterns. Patients with EPs were younger (40.8 vs. 43.3 years; p < 0.01) and had higher baseline BMI (44.5 vs. 43.8 kg/m2; p = 0.046) compared to patients with no EP. They showed slightly higher % total weight loss (%TWL) in the first year (31.9% vs. 30.6%; p < 0.01), but differences diminished over time. At 5 years, SF-BARI scores remained slightly higher in the EP group (84.2 vs. 79.1; p = 0.046). RYGB was performed more frequently (69.9%) and yielded better outcomes than SG. Preoperative EPs, including EDs, do not significantly impact postoperative outcomes after MBS, suggesting a need to reassess guidelines on EDs as contraindications.

Carbohydrate-responsive element binding protein (ChREBP) and Max-like protein X (MLX) form a heterodimeric transcription factor complex that couples intracellular sugar levels to carbohydrate and lipid metabolism. To promote the expression of target genes, two ChREBP-MLX heterodimers form a heterotetramer to bind a tandem element with two adjacent E-boxes, called carbohydrate-responsive element (ChoRE). How the ChREBP-MLX hetero-tetramerization is achieved and regulated remains poorly understood. Here, we show that MLX phosphorylation on an evolutionarily conserved motif is necessary for the heterotetramer formation on the ChoRE and the transcriptional activity of the ChREBP-MLX complex. We identified casein kinase 2 (CK2) and glycogen synthase kinase 3 (GSK3) as MLX kinases. High intracellular glucose-6-phosphate accumulation inhibits MLX phosphorylation and heterotetramer formation on the ChoRE, impairing ChREBP-MLX activity. Physiologically, MLX phosphorylation is necessary in Drosophila to maintain sugar tolerance and lipid homeostasis. Our findings suggest that MLX phosphorylation is a key mechanism for the ChREBP-MLX heterotetramer formation to regulate carbohydrate and lipid metabolism.

Metabolic and bariatric surgery (MBS) has been an established treatment option for patients with Type 2 diabetes mellitus (T2DM), but there is a relative paucity of evidence-based guidelines on preoperative, operative, and postoperative considerations concerning metabolic surgery for T2DM patients. To address this gap, we initiated a Delphi consensus process with a diverse group of international multidisciplinary experts. We embarked on a Delphi consensus-building exercise to propose an evidence-based expert consensus covering various aspects of MBS in patients with T2DM. We defined the scope of the exercise and proposed statements and surveyed the literature through electronic databases. The literature summary and voting process were conducted by 52 experts, who evaluated 44 statements. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Consensus, defined as > 80

Importance:Metabolic bariatric surgery is the most effective and durable treatment for weight loss and improvement of cardiovascular diseases. With sleeve gastrectomy now surpassing gastric bypass as the most common procedure worldwide, comparing these procedures' associations with major adverse cardiac events (MACE) is needed. Objective:To compare the risk of MACE among individuals undergoing gastric bypass or sleeve gastrectomy. Design, Setting, and Participants:This population-based, inverse probability-weighted cohort study was conducted using administrative claims data from Switzerland among adults undergoing gastric bypass or sleeve gastrectomy for obesity treatment between January 2012 and December 2022. Inpatient individuals with a primary or secondary discharge procedure code for gastric bypass or sleeve gastrectomy were eligible for inclusion. Data were analyzed from April 2024 to September 2025. Exposure:Gastric bypass vs sleeve gastrectomy. Main Outcomes and Measures:A weighted cohort was analyzed to study the primary outcome of 4-point MACE, including acute myocardial infarction, ischemic stroke, hospitalizations for heart failure, and all-cause mortality. Secondary outcomes were the individual components of MACE, surgical reinterventions, and associated complications. Results:Of 39 067 patients, 30 270 patients (77.5%) underwent gastric bypass and 8798 patients (22.5%) underwent sleeve gastrectomy. Median (IQR) patient age was 42 (35-50) years, and 28 560 patients (73.1%) were women. A total of 23 708 patients (60.7%) had a body mass index (calculated as weight in kilograms divided by height in meters squared) of 40 or higher. After weighting, over a median (IQR) follow-up of 5.1 years (2.6-7.6), the primary outcome occurred in 577 patients in the gastric bypass group (1.9%) and 264 patients in the sleeve gastrectomy group (3.0%), with incidence rates of 3.96 and 5.10 per 1000 patient-years, respectively (hazard ratio [HR], 0.75; 95% CI, 0.64-0.88). This difference was primarily driven by lower rates of acute myocardial infarction (HR, 0.63; 95% CI, 0.46-0.86). No differences were observed in ischemic stroke, hospitalization for heart failure, and all-cause mortality. Both short- and long-term secondary outcomes favored gastric bypass over sleeve gastrectomy, except for higher rates of revision surgery and immediate postoperative complications. Conclusions and relevance:In this inverse probability-weighted cohort study, for patients undergoing metabolic bariatric surgery, gastric bypass was associated with lower rates of MACE than sleeve gastrectomy over a follow-up period of up to 11 years. Known postoperative complications were confirmed for both gastric bypass and sleeve gastrectomy.

BackgroundRoux-en-Y gastric bypass may present long-term complications that require revisional surgery or even reversal to normal anatomy. Data on the indications, surgical technique, and outcomes of RYGB reversal remain scarce.MethodsWe identified 48 cases of RYGB reversals with complete 90-day follow-up within a multi-centric international retrospective database of elective secondary bariatric surgery. The operations were performed between 2010 and 2024 in high-volume referral centers in Europe and USA. Data were collected on body weight, associated diseases, and on surgical outcomes up to 1-year postoperatively.ResultsPatients were mainly female (81.3%) with a median age of 50 years (IQR 39-56). RYGB reversal was performed 7 years (median) after primary RYGB in patients with a BMI of 23.9 kg/m2 (IQR 20-27). Half of the patients underwent at least 1 bariatric revision before the reversal. Main indications for reversal were dumping syndrome (33.3%), excessive weight loss (29.2%), marginal ulcer (14.6%), malabsorption (12.5%), and abdominal pain (10.4%). Rate of conversion to open surgery was 8.3%, and the postoperative complications during the first year reached 50%, including 31.3% Clavien-Dindo grade I-II, 16.7% grade III-IV complications, and one death. At 1 year, the mean BMI of the cohort increased by 18% to 28.25 kg/m2; only 1 patient reached pre-RYGB BMI.ConclusionAlthough RYGB is a theoretically reversible procedure, normal anatomy is re-established only in selected cases which are refractory to medical therapy and often also to revisional bariatric surgery. RYGB reversals entail high morbidity, while the extent of recurrent weight gain at 1-year post-reversal seems to allow patients to remain below the threshold of severe obesity.

BACKGROUND:The effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on postoperative esophageal motility and its clinical significance is poorly understood. OBJECTIVES:To investigate the effect of SG and RYGB on esophageal motility and distal esophageal acid exposure time at least 5 years after surgery. SETTING:Prospective clinical study conducted in 2 academic hospitals in Switzerland. METHODS:Patients who underwent SG and RYGB were invited at least 5 years after surgery to undergo upper endoscopy, high-resolution manometry (HRM) and wireless pH measurement. Primary outcome was presence of esophageal motility disorders. Exploratory outcomes included presence of esophagitis, Barrett's esophagus, esophageal acid exposure, and validated symptom questionnaires. RESULTS:A total of 113 patients (49 SG and 64 RYGB) underwent HRM and pH monitoring 7 ± 1.6 years after bariatric-metabolic surgery. Integrated-relaxation-pressure was 4.3 ± 3.9 mm Hg after SG and 4.2 ± 3.8 mm Hg after RYGB (P = .89). Average distal contractile integral was 2931 ± 2102 mm Hg-cm-s after SG and 3530 ± 3454 mm Hg-cm-s after RYGB (P = .29). After 100-mL rapid drinking challenge, a hypercontractile or spastic contraction was seen in 37.5% after RYGB and 16.3% after SG (P = .01). Mean esophageal acid exposure time was 11.4 ± 7.9% after SG and 1.3 ± 2.1 after RYGB (P < .0001). Esophagitis was present in 67.3% after SG and 28.1% after RYGB (P < .0001). CONCLUSIONS:Esophageal motility is similar for patients after SG and RYGB and clinically significant motility disorders of the esophagus are rare at long term follow-up. SG leads to significantly more reflux esophagitis, acid reflux and symptoms than RYGB and therefore, endoscopic surveillance should be considered.

Anastomotic ulcers (AU) at the gastroenterostomy are a common postoperative complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). Possible risk factors for ulcer formation include active smoking, the use of non-steroidal anti-inflammatory drugs, increased tension or ischemia at the anastomosis, or factors that increase the acid secretion of the gastric pouch. Therefore, a longer gastric pouch may increase risk of AU formation after LRYGB. This study is a retrospective analysis of prospective collected data from patients undergoing LRYGB between 2009 and 2019 with a minimum follow-up of 2 years. In 2018, we changed the operative technique from short to long gastric pouch LRYGB. We analyzed AU formation, dumping syndrome, age, weight evolution, obesity-associated medical problems, and NSAID in two groups: long (LP-GP) vs. short pouch (SP-GP) LRYGB. A total of 1058 patients were included in the analysis (178 with LP-GP and 880 with SP-GP). A long gastric pouch significantly increased the rate of AU (LP-GP 12.4

BackgroundWith over 1 billion individuals affected globally, obesity and obesity related diseases is now a leading cause of death. Metabolic and bariatric surgery (MBS) has emerged as a cornerstone intervention for severe obesity and its associated comorbidities. Despite its efficacy, postoperative care and follow-up after MBS remains highly variable worldwide.ObjectiveThe PARTNER study aimed to evaluate global clinical practices in the postoperative management following MBS by surveying multidisciplinary healthcare professionals.MethodsThis study was an international online survey conducted between October 2024 and January 2025. A multidisciplinary team developed the questionnaire based on existing literature and international guidelines. The survey assessed five domains: follow-up care, postoperative treatment, dietary management, patient support, and measurement of surgical outcomes. Responses were analysed descriptively.ResultsA total of 262 responses were received from 62 countries. Most respondents were bariatric surgeons (72.1%) working in public healthcare systems (73.3%). While 78.7% reported conducting three-month postoperative reviews, only 23.7% offered indefinite follow-up. Hybrid models of care (virtual and in-person) were common (56.9%). VTE prophylaxis and postoperative PPI use were recommended by 64.1% and 84.3% respectively. Nearly all respondents (98.1%) provided dietary advice, with protein and micronutrient supplementation widely endorsed. Only 56.1% routinely referred patients for psychological follow-up. Definitions of surgical success and failure varied widely, with inconsistent objective outcome measures.ConclusionThe PARTNER study reveals significant international variation in postoperative management practices following MBS. These findings underscore the need for more standardized, evidence-based guidelines to improve long-term outcomes and equity of care worldwide.

Background Patients with initial body mass index > 50 kg/m(2) are vastly under-represented in randomized clinical trials demonstrating similar weight loss and diabetes remission rates after sleeve gastrectomy and Roux-en-Y gastric bypass. Methods Propensity score matching 1 : 1 was used to compare outcomes regarding weight loss and diabetes control after sleeve gastrectomy and Roux-en-Y gastric bypass in patients with body mass index > 50 kg/m(2) between 2012 and 2022 in a cohort from 13 centres in six European countries. The primary endpoint was percentage total bodyweight loss; secondary endpoints were diabetes remission rate and rate of persistent body mass index > 40 kg/m(2). Results In total, 3976 of 8160 patients were matched and included in the analysis (1988 in each group). Median age at baseline was 40.0 (range 16-76) years in the sleeve gastrectomy group and 39.5 (15-71) years in the Roux-en-Y gastric bypass group. Median body mass index at baseline was 56.2 (range 50.0-100.0) and 54.3 (50.0-83.9) kg/m(2), respectively (P < 0.001). The follow-up rate was 70.5% at 1 year and 24.4% at 5 years. Percentage total bodyweight loss at 1 and 5 years after sleeve gastrectomy was 30.2 (2.2-63.7) and 25.4 (-4.8 to 56.0)%, respectively, versus 31.2 (7.4-54.5) and 28.2 (-6.6 to 62.9)% in the Roux-en-Y gastric bypass group (P < 0.001 between groups in both time points). The prevalence of persistent body mass index > 40 kg/m(2) after 1 and 5 years was 42.7 and 57.6%, respectively, after sleeve gastrectomy versus 24.5 and 39.2% after Roux-en-Y gastric bypass (P < 0.001 between groups in both time points). A 5-year follow-up, the prevalence of a pathological haemoglobin A1c level (> 6.5%) was 12.9% after sleeve gastrectomy and 11.6% after Roux-en-Y gastric bypass (P = 0.323). Conclusion This study suggests that Roux-en-Y gastric bypass results in greater weight loss than sleeve gastrectomy in patients with body mass index > 50 kg/m(2), whereas improvements in diabetes appear comparable between procedures.

Objective The aim of this study was to examine whether glucose tolerance, metabolomic profile, and gut microbiota composition is influenced by regular intake of erythritol or xylitol in non-diabetic, obese patients.Background Sugar alcohols such as erythritol and xylitol are on the rise as substitutes for sugar in the food industry and are being suggested for individuals managing obesity and diabetes. Despite their widespread usage and the general perception of safety, there is a notable absence of human trials that delve into their possible impacts on metabolism and the composition of gut microbiota.Methods Obese volunteers (n = 64; BMI: 37.9 ± 0.7 kg/m2; age: 34.2 ± 1.1 years, 70.3% female) were recruited in Switzerland, Russia and Norway. Participants were randomized to three groups (A = xylitol, B = erythritol, C = controls), and received: i) 36 g erythritol, or ii) 24 g xylitol per day, or iii) no treatment (control group) over a period of 7 weeks. At baseline and 7 weeks post-treatment, body weight, abdominal circumference, and blood pressure were measured; an oral glucose tolerance test (oGTT) was carried out; blood samples were collected to assess glycemic control (fasting glucose and insulin, HOMA-IR, fructosamine, AUC glucose/insulin during an oGTT), blood lipid profile, hepatic enzymes, inflammatory markers, and markers of intestinal permeability. Food diaries were collected, gastrointestinal symptoms were assessed by means of a validated questionnaire (GSRS), and stool consistency and form described by use of the Bristol Stool Scale (BSS). Changes in metabolomics patterns (plasma and urine) and gut microbiota composition were assessed by Ultra-Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC-MS) and by 16S rDNA amplicon sequencing.Results Although there was no effect on instantaneous and dynamic metabolic homeostasis readouts (fasting blood glucose, insulin HOMA-IR and oGTT), we report a significant effect of sweeteners intake on medium-term glycemic control (fructosamine) after 7 weeks. We show that gut microbiota and metabolomic profiles track the individual fructosamine response to sweetener intake through a range of taxa and pathways. Lipids and carnitines of microbial origin (propionyl-, butyryl- and phenylacetyl- carnitines), indoles and bile acids modulate the fructosamine response to sweetener intake. Whilst some of these metabolites show concordant associations in normoglycemic and prediabetic volunteers, we found that microbiome metabolite associations differed based on prediabetes status, typically for phenylacetylcarnitine, trimethylamine N-oxide and benzoate metabolism.Conclusions Our study adds to the ongoing debate on sweeteners, and how the microbiome impacts glycemic responses to sweetener intake, suggesting a switch from glucose to lipid utilization and a shift in immune metabolic mediators mediated by the microbiome.

Importance:Reports on long-term outcomes from randomized clinical trials comparing laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are scarce. Objective:To compare long-term weight and metabolic outcomes, reoperation rates, and quality of life for patients undergoing SG vs RYGB at 10 years and beyond. Design, Setting, and Participants:The SM-BOSS (Swiss Multicenter Bypass or Sleeve Study) randomized clinical trial was conducted from January 2007 to November 2011 at 4 bariatric centers in Switzerland. (The last follow-up was obtained in July 2023.) A total of 3971 patients with severe obesity were assessed, and 217 patients were enrolled and randomized to undergo SG or RYGB. Interventions:Laparoscopic SG or RYGB. Main Outcomes and Measures:The primary outcome of the SM-BOSS trial was the percentage excess body mass index loss (%EBMIL) at 5 years. The present study reports on the long-term weight and metabolic outcomes at 10 years and beyond, including changes in weight and obesity-related diseases, reoperation rates, and quality of life. Results:Of 217 patients randomized to undergo SG or RYGB, mean (SD) age was 42.5 (11.1) years, mean (SD) baseline BMI was 43.9 (5.3), and 156 patients (71.9%) were female. Of 217 patients, 110 patients were randomized to RYGB and 107 to SG. Complete 10-year follow-up is available for 65.4% of patients. In the intention-to-treat population, mean (SD) %EBMIL was 60.6% (25.9) after SG and 65.2% (26.0) after RYGB (P = .29). Patients who underwent SG had significantly higher conversion rates because of insufficient weight reduction or reflux compared to RYGB (29.9% vs 5.5%; P < .001). Patients undergoing RYGB had significantly higher mean (SD) %EBMIL compared to SG after 10 years in the per-protocol (PP) population (65.9% [26.3] vs 56.1% [25.2]; P = .048). However, mean (SD) percentage total weight loss was not significantly different between groups (RYGB: 27.7% [10.8]; SG: 25.5% [15.1]; P = .37). SG patients had significantly more de novo gastroesophageal reflux (GERD) compared with RYGB (P = .02). Conclusions and Relevance:In the SM-BOSS randomized clinical trial, RYGB led to significantly higher %EBMIL in the PP population compared with SG beyond 10 years of follow-up, with better results for GERD. Patients undergoing SG experienced a significantly higher number of conversions to different anatomy compared with RYGB. Trial Registration:ClinicalTrials.gov Identifier NCT00356213.

Importance Reports on long-term outcomes from randomized clinical trials comparing laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are scarce. Objective To compare long-term weight and metabolic outcomes, reoperation rates, and quality of life for patients undergoing SG vs RYGB at 10 years and beyond. Design, Setting, and Participants The SM-BOSS (Swiss Multicenter Bypass or Sleeve Study) randomized clinical trial was conducted from January 2007 to November 2011 at 4 bariatric centers in Switzerland. (The last follow-up was obtained in July 2023.) A total of 3971 patients with severe obesity were assessed, and 217 patients were enrolled and randomized to undergo SG or RYGB. Interventions Laparoscopic SG or RYGB. Main Outcomes and Measures The primary outcome of the SM-BOSS trial was the percentage excess body mass index loss (%EBMIL) at 5 years. The present study reports on the long-term weight and metabolic outcomes at 10 years and beyond, including changes in weight and obesity-related diseases, reoperation rates, and quality of life. Results Of 217 patients randomized to undergo SG or RYGB, mean (SD) age was 42.5 (11.1) years, mean (SD) baseline BMI was 43.9 (5.3), and 156 patients (71.9%) were female. Of 217 patients, 110 patients were randomized to RYGB and 107 to SG. Complete 10-year follow-up is available for 65.4% of patients. In the intention-to-treat population, mean (SD) %EBMIL was 60.6% (25.9) after SG and 65.2% (26.0) after RYGB ( P = .29). Patients who underwent SG had significantly higher conversion rates because of insufficient weight reduction or reflux compared to RYGB (29.9% vs 5.5%; P < .001). Patients undergoing RYGB had significantly higher mean (SD) %EBMIL compared to SG after 10 years in the per-protocol (PP) population (65.9% [26.3] vs 56.1% [25.2]; P = .048). However, mean (SD) percentage total weight loss was not significantly different between groups (RYGB: 27.7% [10.8]; SG: 25.5% [15.1]; P = .37). SG patients had significantly more de novo gastroesophageal reflux (GERD) compared with RYGB ( P = .02). Conclusions and Relevance In the SM-BOSS randomized clinical trial, RYGB led to significantly higher %EBMIL in the PP population compared with SG beyond 10 years of follow-up, with better results for GERD. Patients undergoing SG experienced a significantly higher number of conversions to different anatomy compared with RYGB. Trial Registration ClinicalTrials.gov Identifier NCT00356213