Ghusn, Wissam

Metabolic and bariatric surgery is widely recognized as the most effective and durable treatment for the disease of obesity and its associated comorbidities. In recent years, the field has seen significant advancements, introducing numerous innovative surgical options. This review aims to comprehensively examine these emerging surgical techniques, which have recently received endorsement from the American Society for Metabolic and Bariatric Surgery (ASMBS). Additionally, we will explore new technologies and methodologies supported by the latest scientific evidence. Our analysis will include a critical evaluation of the efficacy, safety, and long-term outcomes of these novel approaches, providing a detailed update on the current state of metabolic and bariatric surgery, highlighting key developments and their potential implications for clinical practice.

Background Obesity is intricately associated with type-2 diabetes (T2D) and other cardiovascular conditions, increasing morbidity, mortality, and health care costs. Metabolic and bariatric surgeries (MBS) have shown promising results in significant weight loss and T2D remission, but existing predictive scores for post-MBS diabetes remission do not consider insulin dosage, potentially overlooking a critical factor. Methods A retrospective analysis of patients with T2D who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). The study focused on insulin dosage impact, divided into quartiles, on remission rates post-MBS. The effectiveness of RYGB vs SG was compared within insulin dose quartiles with up to 5 years of follow up. Results A total of 508 patients (64% female, 94.9% White, mean age 53.5 ± 10.5 years, BMI (46.0 ± 8.3 kg/m 2 ) were included in the analysis. This study demonstrates a profound association between insulin dosage quartiles and T2D remission after MBS. Patients with lower insulin requirements showed superior remission rates; those in the lowest quartile had remission rates of 73%, 70%, and 62% at 1, 3, and 5 years, respectively, compared to 34%, 37%, and 36% in the highest quartile ( P < 0.001 across all intervals). RYGB surgery showed a significantly better remission in the second and third insulin quartiles, suggesting its effectiveness over SG for patients with mid-range insulin requirements. Conclusion This study underscores the importance of considering insulin dosage when predicting T2D remission post-MBS. The findings advocate for a more nuanced selection of MBS procedures based on individual insulin profiles, potentially enhancing diabetes remission outcomes.

Abstract Satiation is the physiologic process that regulates meal size and termination, and it is quantified by the calories consumed to reach satiation. Given its role in energy intake, changes in satiation contribute to obesity's pathogenesis. Our study employed a protocolized approach to study the components of food intake regulation including a standardized breakfast, a gastric emptying study, appetite sensation testing, and a satiation measurement by an ad libitummeal test. These studies revealed that satiation is highly variable among individuals, and while baseline characteristics, anthropometrics, body composition and hormones, contribute to this variability, these factors do not fully account for it. To address this gap, we explored the role of a germline polygenic risk score, which demonstrated a robust association with satiation. Furthermore, we developed a machine-learning-assisted gene risk score to predict satiation and leveraged this prediction to anticipate responses to anti-obesity medications. Our findings underscore the significance of satiation, its inherent variability, and the potential of a genetic risk score to forecast it, ultimately allowing us to predict responses to different anti-obesity interventions.

Background: Endoscopic sleeve gastroplasty (ESG) is a safe and effective obesity treatment. The individualized metabolic score (IMS) is a validated score that uses preoperative variables predicting T2D remission (DR) in bariatric surgery. Objectives: We evaluated the applicability of using the IMS score to predict DR in patients after ESG. Design/Methods: We performed a retrospective review of patients with obesity and T2D who underwent ESG. We calculated DR, IMS score, and severity, and divided patients based on IMS category. Results: The cohort comprised 20 patients: 25% (5) mild, 55% (11) moderate, and 20% (4) severe IMS stages. DR was achieved in 60%, 45.5%, and 0% of patients with mild, moderate, and severe IMS scores ( p = 0.08), respectively. IMS score was significantly associated with DR ( p = 0.03), with the area under the curve of the receiver operating characteristic for predicting DR 0.85. Conclusion: These pilot data demonstrate that the IMS score appears to be useful in predicting DR after ESG.

Purpose of review This review examines the complex relationship between obesity and inflammatory bowel disease (IBD), encompassing their potentially shared pathogenesis, the impact of obesity on the natural history and treatment outcomes of IBD, and the management of obesity in the patient with IBD. Recent findings Obesity represents a state of chronic inflammation that may not only contribute to IBD pathogenesis, but also influence disease progression, complications, and response to treatment. Increased visceral adiposity may carry negative prognostic implications for disease and treatment-specific outcomes. Antiobesity medications, endoscopic bariatric therapies, and even bariatric surgery may be effective and well tolerated in selected patients with IBD. Summary The intersection of obesity and IBD presents a significant clinical challenge, with obesity influencing the natural history of IBD and potentially affecting treatment efficacy. As obesity prevalence among IBD patients rises, a tailored approach to management is crucial, taking into account the individualized risks and benefits of various treatment strategies, including lifestyle interventions, pharmacotherapy, endoscopic procedures, and bariatric surgery.

Purpose of review Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility. Recent findings Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility. Summary Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.

Abstract Aims To compare weight loss outcomes between patients starting semaglutide who had previously been on another anti‐obesity medication (AOM) compared to those who were AOM‐naïve. Materials and Methods We performed a retrospective study in patients with overweight or obesity taking semaglutide for weight loss for a duration of 3 to 12 months. Our primary endpoint was assessment of percentage of total body weight loss (TBWL) in patients who started semaglutide as their first AOM (AOM‐naïve) compared to those who started semaglutide and had previously taken another AOM (non‐AOM‐naïve). The secondary outcome was a comparison of the proportions of patients achieving ≥5%, ≥10%, ≥15% and ≥20% TBWL between the groups. Our endpoints were analysed using independent t ‐tests and ANOVA/ANCOVA for continuous variables and Pearson's test for categorical variables. Results This study included 305 patients. Outcomes of semaglutide treatment were superior in AOM‐naïve patients ( n = 231) compared to non‐AOM‐naïve patients ( n = 74) at 3 (6.3% vs. 3.8%), 6 (10.6% vs. 6.7%), 9 (14.0% vs. 9.1%) and 12 months (14.3% vs. 10.6%; p < 0.0001 at 3, 6 and 9 months, and p = 0.01 at 12 months). A greater proportion of patients in the AOM‐naïve group achieved a TBWL ≥ 15% (48% vs 21%; p = 0.02) and ≥20% (27% vs 4% p < 0.01) at 12 months. Conclusion The use of semaglutide in patients with previous intake of other AOMs was associated with inferior weight loss outcomes in comparison to patients who were AOM‐naïve.

Abstract Objective To compare weight loss response and changes in cardiometabolic risk markers in postmenopausal women using semaglutide with and without menopause hormone therapy (HT) use. Methods Retrospective cohort study of postmenopausal women treated with semaglutide for overweight or obesity for ≥3 months. Endpoints: total body weight loss percentage (TBWL%) at 3, 6, 9, and 12 months after semaglutide initiation; and percentage of women achieving ≥5% and ≥10% TBWL and changes in cardiometabolic risk markers (glucose, blood pressure, and lipids) at 12 months. Results There were 16 women on HT and 90 on no-HT; mean age 56 ± 8 vs 59 ± 8 yr, P = 0.2 and mean BMI 36 ± 5 vs 39 ± 8 kg/m2, P = 0.1; respectively. Among women on no-HT, White race, dyslipidemia, and depression were more prevalent. Women on HT had a higher TBWL% at 3, 6, 9, and 12 months: 7 ± 3% vs 5 ± 4%, P = 0.01; 13 ± 6% vs 9 ± 5%, P = 0.01; 15 ± 6% vs 10 ± 6%, P = 0.02; and 16 ± 6% vs 12 ± 8%, P = 0.04; respectively. After adjusting for potential confounders, this association remained significant across time. At 12 months, a greater percentage of women on HT achieved ≥5% and ≥10% TBWL. Both groups experienced an improvement in cardiometabolic risk markers. Conclusion In postmenopausal women with overweight or obesity treated with semaglutide, HT use was associated with an improved weight loss response. This association was maintained when adjusted for confounders. Larger studies should be conducted to confirm these results.

AbstractBackgroundAccelerated gastric emptying (GE) is a trait seen in obesity. Mutations in the hypothalamic leptin‐melanocortin 4 receptor (Leptin‐MC4R) pathway have been associated with obesity. We sought to investigate the association of leptin‐MC4R pathway variants and GE in patients with obesity.MethodsThis is a cross‐sectional study of patients with a history of severe obesity that were genotyped and completed a GE test by scintigraphy. We evaluated the percentage of GE (GE %) at 2 and 4 h between both groups using ANCOVA with weight and sex as covariates. We subdivide patients into carriers based on the location of the identified variants (i.e., upstream or downstream of the Leptin‐MC4R pathway) and compared them with noncarriers using ANOVA. Results are presented as mean and standard deviation (± SD).Key ResultsA total of 95 patients; nine carriers (67% females; 39.78 ± 12.33 years; BMI: 49.14 ± 12.96 kg/m2) and 86 noncarriers (87% female; 49.98 ± 13.74 years; BMI: 40.75 ± 6.29 kg/m2) were included. At 2 and 4 h, carriers had a delayed GE when compared noncarriers (p = 0.03 and p = 0.005, respectively). In carriers, when compared upstream carriers vs. downstream carriers vs. noncarriers by location there was a significant difference in GE among groups at 2 h and at 4 h (p = 0.02 and p = 0.01, respectively).Conclusions & InferencesCarriers of heterozygous variants in the Leptin‐MC4R pathway had a delayed GE compared to noncarriers. These findings point the important relationship between the Leptin‐MC4R pathway and gastric motility.