GLP-1 signaling-regulated SNAP25 is involved in improved insulin secretion in diabetic GK rats after Roux-en-Y gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved ß-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of ß-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND RESULTS: RYGB or sham surgery was conducted in GK rats. mRNA and protein expression of SNAP25 was assessed by qPCR and Western blot, respectively. Occupancy of CREB and acetyltransferase CBP and acetylation of histone H3 (ACH3) at the Snap25 promoter were determined using ChIP assay. RYGB led to increased SNAP25 expression and CREB phosphorylation in islets from GK rats. Increased SNAP25 improved GSIS in ß-cells cultured in high glucose conditions. Consistent with increased plasma GLP-1 after RYGB, GLP-1R agonist exendin4 increased SNAP25 expression and CREB phosphorylation in ß-cells. Mechanistically, exendin4 promoted the recruitment of CREB and CBP, thereby increasing ACH3 at the Snap25 promoter. Consistently, inhibition of CBP attenuated the effect of exendin4 on SNAP25 expression. Furthermore, the knockdown of SNAP25 diminished the increase of GSIS potentiated by chronic GLP-1 culture in INS-1 832/13 cells. CONCLUSIONS: Our findings unravel the novel mechanisms of RYGB-enhanced SNAP25 expression in ß-cells, and SNAP25 may contribute to the improved ß-cell secretory function induced by RYGB.

Third time's a charm: band to sleeve to bypass.

BACKGROUND: Adjustable gastric bands (AGB) are frequently converted to sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) due to weight recurrence or band complications. Such conversions carry a higher-risk than primary procedures. Some patients undergo two conversions-from AGB to SG, and subsequently from SG to RYGB. This presents a unique situation with limited literature on indications and complication rates associated with these double conversions. METHODS: We examined the 2020-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use File to evaluate conversions from AGB to SG and then to RYGB. Patient and operative characteristics, along with outcomes, were evaluated. Descriptive statistics were applied. RESULTS: We identified 276 patients who underwent a conversion from AGB to SG and then to RYGB. The primary reason for the second conversion (SG to RYGB) was gastroesophageal reflux disease (GERD) at 55.1%, followed by inadequate weight loss or weight regain (IWL/WR) at 36.9%. The remaining reasons included dysphagia, nausea, vomiting, or others. Patients converted for IWL/WR demonstrated a higher baseline body mass index and prevalence of sleep apnea compared to other cohorts (both p < 0.001). Meanwhile, patients in the "other reasons" group had the highest rate of open surgical approaches (9.1%) and concurrent lysis of adhesions (p = 0.001 and p = 0.022), with correspondingly higher rates of anastomotic leak, reoperations, serious complications, and mortality. CONCLUSIONS: Patients undergoing double conversions (AGB to SG to RYGB) do so primarily for GERD or IWL/WR. Further research is required to better define the optimal primary operation for each patient, aiming to reduce the necessity for multiple conversions.

Comparison of weight loss after Roux-en-Y gastric bypass in Helicobacter pylori-negative and Helicobacter pylori eradicated patients during five years follow-ups.

PURPOSE: Helicobacter pylori (HP) is the most common human infection that has affected up to 50% of the population worldwide. The relationship between HP eradication and weight loss is under debate. The present study aimed to compare weight loss outcomes after Roux-en-Y gastric bypass (RYGB) in HP-negative (HP-) and HP-eradicated (HPe) patients during five years follow-ups. METHODS: This retrospective cohort study was conducted on 305 patients aged 18 and more with severe obesity, who underwent primary RYGB from February 2014 to November 2017. The HP-negative and HP-eradicated patients were evaluated for weight loss outcomes during five years follow-ups. RESULTS: Patients' mean age, mean weight, and mean body mass index were 38.78 ± 9.9, 114.8 ± 13.6, and 43.37 ± 2.55, respectively. 27.2% of patients who were HP-positive were treated before RYGB. There was no significant difference between the HP- and HPe patients in terms of total weight loss percent (%TWL), 12 to 60 months after RYGB. Excess weight loss percent (%EWL) was higher in HPe patients compared to HP- patients (P = 0.04) at 12-month after RYGB. However, there was no difference in %EWL between these two groups of patients, 36 and 60 months after RYGB. CONCLUSION: The results of the present study showed that TWL% had no significant difference in HP- and HPe groups during five years follow-ups after RYGB. The %EWL was higher in HPe patients only at 12 months after RYGB and the difference did not persist over time.

Single anastomosis duodenal switch versus Roux-en-Y gastric bypass in patients with BMI ≥ 50 kg/m2: a multi-centered comparative analysis.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has consistently demonstrated excellent weight loss and comorbidity resolution. However, outcomes vary based on patient's BMI. Single anastomosis duodeno-ileostomy with sleeve (SADI-S) is a novel procedure with promising short-term results. The long-term outcomes of SADI-S in patients with BMI ≥ 50 kg/m2 are not well described. We aim to compare the safety and efficacy of SADI-S with RYGB in this patient population. METHODS: We performed a multicenter retrospective study of patients with a BMI ≥ 50 kg/m2 who underwent RYGB or SADI-S between 2008 and 2023. Patient demographics, peri- and post-operative characteristics were collected. Complication rates were reported at 6, 12, 24, and 60 months postoperatively. A multivariate linear regression was used to evaluate and compare weight loss outcomes between both procedures. RESULTS: A total of 968 patients (343 RYGB and 625 SADI-S; 68.3% female, age 42.9 ± 12.1 years; BMI 57.3 ± 6.7 kg/m2) with a mean follow-up of 3.6 ± 3.6 years were included. Patients who underwent RYGB were older, more likely to be female, and have a higher rate of sleep apnea (p < 0.001), hypertension (p = 0.015), dyslipidemia (p < 0.001), and type 2 diabetes (p = 0.016) at baseline. The rate of bariatric surgery-specific complications was lower after SADI-S compared to RYGB. We reported no bariatric surgery related deaths after 1 year following both procedures. SADI-S demonstrated statistically higher and sustained weight loss at each time interval compared to RYGB (p < 0.001) even after controlling for multiple confounders. Lastly, the rate of surgical non-responders was lower in the SADI-S cohort. CONCLUSIONS: In our cohort, SADI-S was associated with higher and sustained weight-loss results compared to RYGB. Comorbidity resolution was also higher after SADI-S. Both procedures demonstrate a similar safety profile. Further studies are required to validate the long-term safety of SADI-S compared to other bariatric procedures.

The association between microvascular and macrovascular diseases and diabetes remission after bariatric surgery.

BACKGROUND: Type-2 diabetes mellitus (T2DM) results in detrimental vascular complications including both microvascular and macrovascular diseases. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective weight-loss therapies that enhance T2DM remission. However, limited data are present regarding the association between diabetes-associated diseases before RYGB and SG with T2DM remission. METHODS: This is a retrospective cohort study in patients with T2DM who underwent RYGB or SG. We collected data on preoperative microvascular (i.e., retinopathy, nephropathy, and neuropathy) and macrovascular (coronary artery disease, cerebrovascular accidents, and peripheral artery disease) diabetes-associated diseases. Our end points included assessment of association and cumulative effect of diabetes-associated diseases and disease remission. We also performed a multivariate logistic regression to evaluate the parameters associated with T2DM remission. RESULTS: A total of 536 patients (67% female, 94% White) were included in this study. Patients without diabetes-associated diseases had an OR of 2.72 (95% CI 1.92 to 3.88) to achieve T2DM remission compared to patients with diabetes-associated diseases (27.9% vs 59.4%; p < 0.001). Importantly, there was an additive effect of the number of diabetes-associated diseases on the T2DM remission (p < 0.001). We demonstrate a significant association between HbA1c (p < 0.001), number of diabetes medications (p < 0.001), T2DM duration (p < 0.001), surgery type (p = 0.009), and insulin use (p = 0.04) with T2DM remission. CONCLUSION: Patients with presurgical diabetes-associated diseases had a lower remission rate after RYGB and SG. Not only do these complications represent a more practical and consistent variable to predict T2DM remission, but also help planning a multidisciplinary management of patients with more severe T2DM.

Comparative analysis of linear- and circular-stapled gastrojejunostomies in Roux-en-Y gastric bypass: a focus on postoperative morbidity using the comprehensive complication index.

PURPOSE: The linear-stapled (LSA) and the circular-stapled anastomosis (CSA) are the two most commonly performed techniques for the gastrojejunostomy (GJ) during laparoscopic Roux-en-Y gastric bypass (RYGB). This study compared the outcome after both techniques with special focus on postoperative morbidity using the comprehensive complication index (CCI). METHODS: Five hundred eighty-eight patients operated between 01/2010 and 12/2019 were included in the final analysis and divided in two cohorts according to the surgical technique of the GJ (LSA (n = 290) or CSA (n = 298)). Before 09/2016, the CSA was exclusively performed for the GJ, while after 09/2016, the LSA was solely used. RESULTS: The mean CCI for patients with Clavien-Dindo complication grade ≥ 2 within the first 90 days after RYGB was 31 ± 9.1 in the CSA and 25.7 ± 6.8 in the LSA group (p < 0.001), both values still below the previously published benchmark cutoff (≤ 33.73). The C-reactive Protein (CRP)-levels on postoperative days (POD) 1 and 3 as well as the use of opioids on POD 1 were significantly higher in the CSA- than in the LSA-group (all p < 0.001). There were significantly more internal herniations in the CSA group during the first 24 postoperative months (p < 0.001). CONCLUSION: Patients after RYGB with CSA were found to have higher CCI values during the first 90 PODs compared to patients in which the LSA was applied. To achieve optimal outcomes in terms of patient morbidity, the LSA seems to be the superior technique for GJ in RYGB.

The role of diabetes severity scores in predicting disease remission in patients with BMI > 50 kg/m2 undergoing Roux-En-Y gastric bypass and sleeve gastrectomy: a multi-centered study.

BACKGROUND: Roux-En-Y gastric bypass (RYGB) and Sleeve Gastrectomy (SG) have shown to be two of the most effective interventions to enhance weight loss and associated type-2 diabetes mellitus (T2DM) remission. However, a significant number of patients, particularly with BMI ≥ 50 kg/m2, do not achieve T2DM remission after bariatric surgeries. The individualized metabolic surgery (IMS) and Robert et al. scores are two scores that characterize T2DM severity and predict disease remission after bariatric surgeries. We aim to assess the validity of these scores in predicting T2DM remission in our cohort of patients with BMI ≥ 50 kg/m2 with long-term follow-up. METHODS: This is a retrospective cohort study of all patients with T2DM, have a BMI ≥ 50 kg/m2, and underwent RYGB or SG in two different US bariatric surgery centers of excellence. The study endpoints included validating the IMS and Robert et al. scores in our cohort and evaluating the presence of any significant differences between RYGB and SG in terms of T2DM remission predicted by each of these scores. Data are presented as mean (standard deviation). RESULTS: A total of 160 patients (66.3% females, mean age 51.0 [11.8] years) had IMS score and 238 patients (66.4% females, age 50.8 [11.4] years) had Robert et al. score data. Both scores predicted T2DM remission in our patients with BMI ≥ 50 kg/m2 with ROC AUC 0.79 for the IMS score and 0.83 for Robert et al. score. Patients with lower IMS scores and higher Robert et al. scores had higher T2DM remission rates. RYGB and SG had similar T2DM remission rates over the long-term follow-up. CONCLUSION: We demonstrate the ability of the IMS and Robert et al. scores to predict T2DM remission in patients with BMI ≥ 50 kg/m2. T2DM remission was shown to decrease with more severe IMS scores and lower Robert et al. scores.

Safety and efficacy of LA-ERCP procedure following Roux-en-Y gastric bypass: a systematic review and meta-analysis.

INTRODUCTION: Rapid weight loss following Roux-en-Y gastric bypass surgery (RYGB) translates to an increased need for endoscopic retrograde cholangiopancreatography (ERCP) intervention. Laparoscopically Assisted Transgastric ERCP (LA-ERCP) has emerged to address the issue of accessing the excluded stomach. This study aims to evaluate the safety and efficacy of LA-ERCP procedure following RYGB. METHODS: The Cochrane, EMBASE, SCOPUS, MEDLINE, Daily and Epub databases were searched from inception to May 2022 using the PRISMA guidelines. Eligible studies reported participants older than 18 years who underwent the LA-ERCP procedure, following RYGB, and outcomes of patients. RESULTS: 27 unique studies met the inclusion criteria with 1283 patients undergoing 1303 LA-ERCP procedures. 81.9% of the patients were female and the mean age was 52.18 ± 13.38 years. The rate of concurrent cholecystectomy was 33.6%. 90.9% of procedures were undertaken for a biliary indication. The mean time between RYGB and LA-ERCP was 89.19 months. The most common intervention performed during the LA-ERCP was a sphincterotomy (94.3%). Mean total operative time was 130.48 min. Mean hospital length of stay was 2.697 days. Technical success was 95.3%, while clinical success was 93.8%. 294 complications were recorded with a 20.6% complication rate. The most frequent complications encountered were pancreatitis (6.8%), infection (6.1%), bleeding (3.4%), and perforation (2.5%). Rate of conversion to open laparotomy was 7%. CONCLUSION: This meta-analysis presents preliminary evidence to suggest the safety and efficacy of LA-ERCP procedure following RYGB. Further investigations are warranted to evaluate the long-term efficacy of this procedure using studies with long-term patient follow-up.

Frequency of cholelithiasis in need of surgical or endoscopic treatment a decade or more after Roux-en-Y gastric bypass.

BACKGROUND: Symptomatic cholelithiasis requiring treatment is a known side effect after Roux-en-Y gastric bypass (RYGB), but reported rates vary greatly. The objectives for this study were to evaluate the long-term frequency of surgical or endoscopic treatment for symptomatic cholelithiasis 10-15 years after RYGB and its relation to self-reported abdominal pain. METHODS: Observational data from 546 patients who underwent RYGB at public hospitals in Central Norway between March 2003 and December 2009 were analyzed. RESULTS: Median follow-up was 11.5 (range 9.1-16.8) years. Sixty-five (11.9%) patients had undergone cholecystectomy prior to RYGB. Out of the 481 patients with intact gallbladder, 77 (16.0%) patients underwent cholecystectomy and six (1.2%) patients had treatment for choledocholithiasis during the observation period. Median time from RYGB to cholecystectomy or treatment of choledocholithiasis was 51 (range 1-160) and 109 (range 10-151) months, respectively. Female sex was associated with an increased risk of subsequent cholecystectomy [OR (95% CI) 2.88 (1.31-7.15)], p < 0.05. There was a higher frequency of self-reported abdominal pain at follow-up [OR (95% CI) 1.92 (1.25-2.93)] among patients who underwent cholecystectomy before or after RYGB. CONCLUSION: With a median follow-up of more than 11 years after RYGB, one in six patients with an intact gallbladder at time of RYGB underwent cholecystectomy, and 1.1% of the patients needed surgical or endoscopic treatment for choledocholithiasis. Patients with a history of cholecystectomy reported a higher frequency of abdominal pain.

Concurrent paraesophageal hernia repair in revisional/conversional laparoscopic Roux-en-Y gastric bypass: propensity score-matched analysis of the MBSAQIP database.

BACKGROUND: Patients requiring concurrent paraesophageal hernia repair (CPHR) have been shown to have favorable outcomes in primary bariatric surgery. However, patients requiring revisional or conversional surgery represent a group of patients with higher perioperative risk. Currently, few reports on concurrent paraesophageal hernia repair utilizing the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database are available. The primary aim of this study was to determine perioperative complications associated with CPHR and the Roux-en-Y gastric bypass (RYGB) as a revisional/conversional operation. METHODS: In this study, patients undergoing revisional/conversional RYGB between 2015 and 2020 were accessed via the MBSAQIP database. Patients were categorized based on the presence of a paraesophageal hernia as a concurrent procedure. Patients who underwent revisional/conversional surgery without additional procedures were utilized for controls. A propensity score-matched cohort was generated and E-analysis utilized to assess unmeasured confounding. RESULTS: After exclusions, 35,698 patients were available. Patients receiving CPHR were more likely to be female (90.79% vs 87.37%; p < 0.001) and have increased frequency of gastroesophageal reflux disease (69.20% vs 51.69%; p < 0.001). However, these patients had lower frequencies of sleep apnea (24.12% vs 30.13%; p < 0.001), hypertension requiring medication (38.51% vs 42.59%; p < 0.001), and decreased frequency of hyperlipidemia (19.44% vs 21.60%;p < 0.001). After matching, 6,231 patient pairs were developed and showed that patients undergoing CPHR were at increased risk of readmission (9.44% vs 7.58%; p < 0.001), intervention (3.56% vs 2.79%; p = 0.018), increased requirement for outpatient dehydration treatment (5.87% vs 4.67%;p = 0.004), and overall increased operation time (169.3 min ± 76.0 vs 153.5 ± 73.3; p < 0.001). However, there were no significant increases in the rates of reoperation, death, postoperative leak complications, or bleeding complications after CPHR. CONCLUSION: Patients undergoing revisional/conversional RYGB with CPHR may be at higher risk for a small number of rare postoperative complications. CPHR is a safe procedure in patients undergoing revisional/conversional RYGB in the short-term postoperative period.

Severity of post-Roux-en-Y gastric bypass dumping syndrome and weight loss outcomes: is there any correlation?

PURPOSE: The present research was conducted to evaluate the effect of the severity of dumping syndrome (DS) on weight loss outcomes after Roux-en-Y gastric bypass (RYGB) in patients with class III obesity. METHODS: The present retrospective cohort study used the dumping symptom rating scale (DSRS) to evaluate the severity of DS and its correlation with weight loss outcomes in 207 patients 1 year after their RYGB. The patients were assigned to group A with mild-to-moderate DS or group B with severe DS. RESULTS: The mean age of the patients was 42.18 ± 10.46 years and their mean preoperative BMI 42.74 ± 5.59 kg/m2. The total weight loss percentage (%TWL) in group B was insignificantly higher than that in group A, but besides that was not significantly different in the two groups. CONCLUSION: The present findings suggested insignificant relationships between the presence and severity of DS after RYGB and adequate postoperative weight loss.

One anastomosis gastric bypass versus Roux-en-Y gastric bypass: a 30-day follow-up review.

BACKGROUND: One anastomosis gastric bypass (OAGB) type procedures have been widely adopted outside the United States. International experience of OAGB commonly suggests improved early postoperative safety with OAGB over Roux-en-Y gastric bypass (RYGB). This study aims to report on the early experience with OAGB in Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) accredited centers, and compare with RYGB in terms of complication rates. METHODS: The MBSAQIP public use files from 2015 to 2018 were used to identify adult patients who underwent primary OAGB and RYGB. Propensity score analysis was used to estimate the marginal population-average differences between OAGB and RYGB patients. Based on the matched samples, McNemar's tests and Wilcoxon signed rank test were carried out for binary and continuous outcomes. P-value < 0.05 was considered statistically significant. RESULTS: Propensity score matching analysis resulted in 279 matched pairs for OAGB and RYGB. Twelve OAGB patients (4.3%) experienced a complication; 3 of them (1.1%) were diagnosed with anastomotic leaks. Compared to 14 (5%) of RYGB patients experiencing a complication; 5 (1.8%) were diagnosed with anastomotic leaks. Reintervention, reoperation and readmission rates for OAGB were 2.5%, 3.2% and 5%, compared to 1.8%, 1.8%, and 3.2% for RYGB. DISCUSSION: Our study supports previous data that suggests OAGB has a similar early safety profile compared to RYGB and perioperative risks of OAGB should not be of a concern regarding its adoption. Conversely, OAGB does not seem to be associated with an improved safety profile over RYGB.

Safety and efficacy of laparoscopic sleeve gastrectomy in patients with portal hypertension with liver function of Childs A.

INTRODUCTION: Advanced liver disease and portal hypertension (PH) are seen as a relative contraindication for bariatric and metabolic surgery. Several studies have shown significant improvement in liver function and liver histology after bariatric surgery. There are very few studies describing bariatric surgery in patients with PH. The purpose of this retrospective study is to evaluate the feasibility and results of laparoscopic sleeve gastrectomy (SG) in patients with PH. MATERIAL AND METHODS: We present our experience of performing laparoscopic SG in 15 patients with evidence of PH. All the patients were Childs Pugh Criteria A. PH was confirmed by the presence of dilated esophageal varices on endoscopy. RESULTS: The mean operative time was 77.33 ± 15.22 min and mean blood loss was 80.67 ± 37.12 ml. The mean length of stay was 2.73 ± 0.59 days. There were no intraoperative or immediate postoperative complications. None of the patients required blood transfusion in the postoperative period. The weight, BMI, Excess body weight loss% (EBWL%), Total weight loss (TWL) and TWL% at 1 year were 86.05 ± 14.40 kg, 31.16 kg/m2 ± 3.82, 63.84% ± 15.24, 31.49 ± 9.54 kg and 26.50 ± 5.42%, respectively. Diabetes and hypertension resolution at 1 year was 80% and 72.72%, respectively. All the patients were followed up for mean 3 ± 1.5 years. There were no immediate or long-term morbidity and mortality noted. CONCLUSION: SG is a feasible and safe option for the treatment of obesity in carefully selected patients with PH with good weight loss and comorbidity resolution.

On measurements of glucagon secretion in healthy, obese, and Roux-en-Y gastric bypass operated individuals using sandwich ELISA.

Glucagon is a key regulator of metabolism and is used in the diagnostic of neuroendocrine tumors. Accurate measurement of glucagon requires both extreme sensitivity and specificity since several peptides are derived from the same proglucagon precursor encoding part of the glucagon sequence and given that glucagon circulates in picomolar concentrations. A sandwich ELISA was recently developed and extensively evaluated; however, this method may not be accurate when measuring glucagon in patients with an enhanced production of proglucagon-derived peptides as seen after Roux-en-Y gastric bypass (RYGB). To overcome this, a modified version of the ELISA was developed. In this study, we evaluate an unmodified and a modified version of the ELISA in healthy individuals, individuals with obesity, and finally in two cohorts of patients following RYGB surgery using different nutrient stimuli to assess glucagon dynamics. Finally, in vitro spike-in recoveries using native glucagon and proglucagon-derived peptides were performed in buffer and in plasma. Our data support that both versions of the ELISA accurately capture endogenous and exogenous glucagon in healthy individuals and in individuals with obesity. However, the unmodified version of the assay may overestimate glucagon levels in patients following RYGB in line with minimal but consistent cross-reactivity to oxyntomodulin and glicentin that both are 50-fold increased after RYGB. Importantly, we did not find any changes between the two protocols at fasted conditions and therefore diagnostics of glucagonomas is not affected by the choice of assay procedure nor the surgical history of the patient (RYGB).

GLP-1: 10-year follow-up after Roux-en-Y gastric bypass.

PURPOSE: Glucagon-like peptide-1 (GLP-1) is a hormone widely studied in the short-term postoperative follow-up of Roux-en-Y gastric bypass due to its elevation and association with improvement of the glucose metabolism, but there are few studies in 10 years after RYGB follow-up with the same patient. METHODS: Twenty morbidity obesity patients were submitted to RYGB; these patients were divided into two groups: normal glucose-tolerant morbidly obese patients (NGT) 11 patients and abnormal glucose metabolism morbidly obese patients (AGM) 9 patients. Oral glucose tolerance test (OGTT) was done during four different periods: T1 (first evaluation), T2 (pre-surgery), T3 (9 months after surgery) and T4 (10 years after surgery). RESULTS: Groups were matched for age and gender, and as NGT and AGM had BMI of 46.31 ± 5.03 kg/m2 and 50.87 ± 10.31 kg/m2. After 10 years of RYGB, they were obesity grade I with BMI for NGT 32.45 ± 4.99 kg/m2 and AGM 34.85 ± 4.46 kg/m2. Plasma glucose levels decreased NGT group at T4 period had a significant reduction at 120 min after OGTT for NGT 55.49 ± 17.15 mg/dL (p˂0.001). Insulin levels changed from T1 to T4 for the NGT group. GLP-1 curves were statistically different between the NGT and AGM groups. The AGM group had a higher mean for GLP-1 secretion at T4 period and at 30 min of OGTT 63.85 ± 37.98 pmol/L when compared to NGT 50.73 ± 24.82 pmol/L with AGM > NGT with p˂0.001. CONCLUSION: Evaluation of the same patient during 4 different periods shows that, even with weight regain, after 10-years of RYGB high levels of GLP-1 remained which can be associated with metabolic improvement especially at the NGT group.

Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations.

Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.

Circulating Adipokines and Hepatokines Serve as Diagnostic Markers during Obesity Therapy.

Allocation of morbidly obese patients to either conservative therapy options-such as lifestyle intervention and/or low-calorie diet (LCD)-or to bariatric surgery-preferably sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB)-represents a crucial decision in order to obtain sustainable metabolic improvement and weight loss. The present study encompasses 160 severely obese patients, 81 of whom participated in an LCD program, whereas 79 underwent RYGB surgery. The post-interventional dynamics of physiologically relevant adipokines and hepatokines (ANGPTL4, CCL5, GDF15, GPNMB, IGFBP6), as well as their correlation with fat mass reduction and improvement of liver fibrosis, were analyzed. Systemic GDF15 was characterized as an excellent predictive marker for hepatic fibrosis as well as type 2 diabetes mellitus. Of note, baseline GDF15 serum concentrations were positively correlated with NFS and HbA1c levels after correction for BMI, suggesting GDF15 as a BMI-independent marker of hepatic fibrosis and T2D in obese individuals. Specific GDF15 cut-off values for both diseases were calculated. Overall, the present data demonstrate that circulating levels of specific adipokines and hepatokines are regulated with therapy-induced fat loss and metabolic improvement and might, therefore, serve as biomarkers for the success of obesity therapy strategies.

Technical aspects and standardization of the totally robotic Roux-en-Y gastric bypass. Results of a single surgeon experience with a 5-year follow-up.

INTRODUCTION: The use of robotics in bariatric surgery is increasing worldwide, with as main objective reducing complications and optimising surgical outcome. This study presents the results of a single surgeon 8-year experience with a totally robotic Roux-en-Y gastric bypass (RYGB). METHODS: A total of 183 consecutive patients underwent a robotic bariatric procedure. A retrospective analysis was performed of all patient files to obtain patient characteristics, weight loss results and per- and postoperative morbidity. For long-term follow-up all patients were contacted one by one. RESULTS: In 155/183 patients, a primary RYGB was performed, 23 procedures were revisional cases and in 5 other procedures were performed. Mean initial weight was 112.07 (±20.5) kg, mean start BMI was 40.8 (±5.36) kg/m2. There were no conversions and no major intraoperative complications. In the early postoperative period we note two revisions; one postoperative bleeding and one missed iatrogenic enterotomy. Mean length of stay in the hospital was 3.50 (±1.20) days. After a mean follow-up of 62.06 (±32.76) months, mean BMI was 28.07 (±4.88) kg/m2 with an % excess body mass index loss of 84.02 (±31.64) %. Patient satisfaction was high, with 95.1% of the patients being happy. The main complaint in the remaining patients was weight regain. CONCLUSION: The robotic RYGB is a safe and reproducible approach to treat morbid obesity. A secure hand-sewn gastrojejunal anastomosis, quick recovery and better ergonomics are the main advantages of this technique.

FXR-mediated epigenetic regulation of GLP-1R expression contributes to enhanced incretin effect in diabetes after RYGB.

In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling and GLP-1R-linked signalling in ß-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP-1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp-1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus increasing histone H3 acetylation at the promoter. These coordinated events bring about increased GLP-1R expression, resulting in greater GLP-1 response in ß-cells. Moreover, ablation of FXR suppressed the stimulatory effects of GLP-1. Thus, this study unravels the crucial role of the BAs/FXR/SRC1 axis-controlled GLP-1R expression in ß-cells, which results in enhanced incretin effect and normalized blood glucose of GK rats after RYGB.

Comparative Effectiveness of Roux-en Y Gastric Bypass Versus Vertical Sleeve Gastrectomy for Sustained Remission of Type 2 Diabetes Mellitus.

BACKGROUND: Bariatric surgery results in rapid weight loss and resolution of comorbidities such as type 2 diabetes mellitus (T2DM). We aimed to determine whether the type of surgical procedure-vertical sleeve gastrectomy (VSG) versus Roux-en-Y gastric bypass (RYGB)-was associated with sustained remission from T2DM, and to identify other independent predictors of sustained remission. METHODS: Using the IBM MarketScan database of privately insured patients in the United States, we performed a retrospective cohort study on individuals aged 18-65 y with T2DM on hypoglycemic medication, who underwent either VSG or RYGB from 2010 to 2016. Remission was defined as no refill of antidiabetic medication 180 d after a patient's medication was expected to run out and recurrence as medication refill after at least 180 d of remission. RESULTS: Of 5119 patients in our cohort, 4127 (81%) experienced remission of T2DM, and 816 (19.8%) of the 4127 patients experienced recurrence. Patients who underwent RYGB had a 24% (HR = 1.24, 95% CI: 1.16, 1.32) increased probability of achieving remission compared with VSG. RYGB had a 36% (HR = 0.64, 95% CI: 0.55, 0.74) decreased risk of recurrence compared with VSG. A higher number of diabetic medications at the time of surgery and a higher Charlson index score were associated with decreased probability of remission and an increased risk of recurrence of T2DM. CONCLUSIONS: While both procedures are initially effective, RYGB may be better than VSG at providing lasting remission of T2DM.