Obesity-related Comorbidities Research Articles

Updates in Bariatric Surgery.

Bariatric surgery is currently the most effective long-term treatment for morbid obesity as well as type-2 diabetes mellitus. The field of metabolic and bariatric surgery has seen tremendous growth over the past decade with dramatically reduced risks. This article aims to provide an update on bariatric surgery, highlighting the latest outcomes, improvements, and challenges in the field. Recently, the American Society of Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) released a major update to the indications for bariatric surgery at BMI ≥35kg/m2 regardless of co-morbidities and 30-34.9kg/m2 with obesity-related comorbidities. Sleeve gastrectomy has emerged as the most popular bariatric procedure in the last 10years with its remarkable efficacy and safety profile. The implementation of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) and Enhanced Recovery After Surgery (ERAS) protocols have significantly improved the quality of care for all bariatric patients. The recent introduction and FDA approval of Glucagon-Like Peptide-1 (GLP-1) agonists for chronic obesity has garnered significant media coverage and popularity, but no guidelines exist regarding its use in relation to bariatric surgery. This update underscores the need for tailored approaches, ongoing research, and the integration of evidence-based medicine and innovations to enhance patient care.

Mind the gap! Factors that predict progression to bariatric surgery indicate that more psychological treatment may be required.

In the UK, the number of adults living with obesity is increasing. Bariatric surgery is an available treatment for those living with a BMI (kg/m2 ) ≥40 and above, or ≥35 with obesity-related comorbidities. Guidelines highlight the importance of providing psychological support pre- and post-surgery owing to the complex psychopathology present in those living with obesity. There are a lack of studies examining which patients proceed to surgery and the factors that predict progression. Routine patient data were collected within one NHS regional service in the UK, comprising 733 patients between 3 August 2018 and 26 July 2019, aged between 17 and 76 years (M = 43.20, SD = 12.32). The only exclusion criteria were patients still awaiting a final decision for surgical outcome at the point of analysis (N = 29), which resulted in 704 patients included in analysis. Binary Logistic Regression revealed those who were more likely to progress to surgery had a lower-level use of maladaptive external substances; lower level of self-harm and/or suicidality, were older in age; had a lower BMI; and had less comorbidities than those who did not progress. Findings support existing literature in that bariatric patients often present with physical and mental health complexity. Two thirds of patients in this study did not progress to surgery. Service commissioning decisions meant that these patients did not have access to psychology treatment. Consequently, in cases where bariatric surgery is considered, a final treatment option and otherwise clinically appropriate, lack of access to specialist services may result in unmet patient need owing particularly to a lack of psychological treatment provision.

Standardized Assessment of Metabolic Bariatric Surgery Outcomes

A standardized definition and reporting of metabolic bariatric surgery (MBS) outcomes is not available for actual clinical practice and science. To assess the feasibility of using a clinically relevant and feasible MBS outcome score (Swiss-Finnish Bariatric Metabolic Outcome Score [SF-BARI Score]). This assessment of a bariatric surgery outcome score is based on the secondary analysis of merged 5-year individual patient data (N = 457) of 2 large randomized clinical trials (Swiss SM-BOSS [Swiss Multicenter Bypass or Sleeve Study], conducted from January 2007 to November 2011, and Finnish SLEEVEPASS [Laparoscopic Gastric Bypass Vs Sleeve Gastrectomy to Treat Morbid Obesity], conducted from March 2008 until June 2010) that compared laparoscopic sleeve gastrectomy with laparoscopic Roux-en-Y gastric bypass in the treatment of severe obesity. This secondary analysis was performed from January 2022 to January 2023. The main outcome was the feasibility of the SF-BARI Score and the SF-BARI Score QOL (quality of life) as tools to assess MBS outcomes. The score includes percentage of total weight loss (%TWL), 4 obesity-related comorbidities (type 2 diabetes, hypertension, dyslipidemia, and obstructive sleep apnea), complications, and QOL, if available. Among the 457 included patients, 323 (70.7%) were female and 134 (29.3%) were male, and the mean (SD) age was 45.6 (10.7) years. Outcomes for the SF-BARI Score were available for 435 patients (95.2%) at 1 year and 398 patients (87.1%) at 5 years and for SF-BARI Score QOL in 289 (63.2%) patients at 1 year and 318 patients (69.6%) at 5 years. The SF-BARI Score was correlated with both the SF-BARI Score QOL (r = 0.96; 95% CI, 0.95-0.96; P < .001) and %TWL (r = 0.86; 95% CI, 0.84-0.89; P < .001) and with the Bariatric Analysis and Reporting Outcome System (r = 0.59; 95% CI, 0.51-0.65; P < .001). Score outcomes were categorized as excellent, very good, good, fair, and suboptimal response. There was a statistically significant difference in scores at 1 vs 5 years (4.0; 95% CI, 1.4-6.6; P = .003), and the gastric bypass group had a higher score compared with the sleeve gastrectomy group (7.4; 95% CI, 3.4-11.5; P < .001). These findings indicate that this metabolic bariatric surgery outcome score is a simple, relevant, and feasible composite tool to define and measure MBS outcomes, enabling standardized reporting. ClinicalTrials.gov Identifiers: NCT00356213 (SM-BOSS) and NCT00793143 (SLEEVEPASS).

IBC-Oxford University2023_BJSPoster_17Bariatric Surgery on Patients with Epilepsy

Abstract Introduction Obesity is a common comorbid condition in patients with epilepsy, its occurrence is multifactorial and antiepileptic medications may contribute to the development of obesity and metabolic syndrome. Bariatric surgery can be offered to patients with epilepsy and obesity related comorbidities. Currently, there is lack of information regarding bariatric surgery on seizure control and antiepileptic drug concentration/toxicity. Methods A retrospective review of a local database was performed in a tertiary centre for Bariatric Surgery. All consecutive patients with epilepsy referred to the Bariatric MDT since 2010 were identified. Standard clinical data, postoperative complications, seizure frequency, antiepileptic therapy and weight loss were extracted. Results We identified 11 patients with epilepsy who underwent Bariatric Surgery (3 Sleeve gastrectomy, 4 gastric bypass, 4 gastric band). The %TWL 1 year after Bariatric Surgery (BS) was 22.4(20-24)%; 3 years following BS was 19.9(5-25)% and 5 years following BS was 18.9(4-24)%. 7 Patients remained seizure free during 5 year follow up after BS, in 3 people their seizure frequency did not change after BS and one patient had a cluster of dissociative seizures. There were no medication side effects reports due to impact of surgery. Conclusion Bariatric Surgery is a safe treatment option for individuals with epilepsy. The majority of patients with epilepsy who underwent bariatric surgery had no worsening in seizure frequency or experienced any medication side effects due to the impact of surgery on absorption. Individuals with morbid obesity and epilepsy can be considered for bariatric surgery. More research is required to adequately explore the impact of BS on patients with epilepsy.

EE630 The Economic Burden of Obesity in 4 Selected South-Eastern European Countries: Healthcare Resource Use and Costs Associated with Obesity-Related Comorbidities

EE630 The Economic Burden of Obesity in 4 Selected South-Eastern European Countries: Healthcare Resource Use and Costs Associated with Obesity-Related Comorbidities

Recent advances in bariatric surgery: a narrative review of weight loss procedures

Bariatric surgery has emerged as a highly effective option for individuals with obesity, offering significant and sustainable weight loss outcomes. This surgical approach involves various procedures that alter the anatomy of the gastrointestinal tract, leading to reduced food intake and nutrient absorption. Established procedures such as sleeve gastrectomy, gastric bypass, adjustable gastric banding, and biliopancreatic diversion with duodenal switch have proven track records. In contrast, emerging options like intragastric balloons, AspireAssist devices, and endoscopic sleeve gastroplasty show promise but require further investigation. Numerous studies have highlighted the remarkable benefits of bariatric surgery, not only in weight loss but also in the resolution of obesity-related comorbidities and significant improvements in quality of life. However, successful outcomes rely on a multidisciplinary approach, encompassing preoperative evaluation, patient selection, comprehensive postoperative care, nutritional support, and psychological counseling. Regular follow-up and adherence to postsurgical recommendations are crucial for sustained weight loss and positive long-term results. As bariatric surgery continues to evolve, tailored procedures based on individual needs and ongoing research hold the potential for even more refined and effective approaches. Through this ongoing advancement, bariatric surgery is poised to offer improved patient outcomes, transforming lives for those grappling with the challenges of obesity.

High Prevalence of Positive Genetic Obesity Variants in Postoperative Bariatric Surgery Patients with Weight Regain Presenting for Medical Obesity Intervention.

Genetic obesity susceptibility in postoperative bariatric surgery weight regain (PBSWR) remains largely unexplored. A retrospective case series of adult (N = 27) PBSWR patients who had undergone genetic obesity testing was conducted between Sept. 2020 and March 2022. frequency of genetic variants in patients experiencing weight regain following bariatric surgery. prevalence of obesity-related comorbidities, nadir BMI achieved post-bariatric surgery, and percent total body weight loss (%TBWL) achieved with obesity pharmacotherapies. Heterozygous mutations were identified in 22 (81%) patients, with the most prevalent mutations occurring in CEP290, RPGR1P1L, and LEPR genes (3 patients each). Median age was 56years (interquartile range (IQR) 46.8-65.5), 88% female. Types of surgery were 67% RYGB, 19% SG, 4% gastric band, and 13% revisions. Median nadir BMI postoperatively was 34.0kg/m2 (IQR 29.0-38.5). A high prevalence of metabolic derangements was noted; patients presented median 80months (IQR 39-168.5) postoperative for medical weight management with 40% weight regain. BMI at initiation of anti-obesity medication (AOMs) was 41.7kg/m2 (36.8-44.4). All received AOM and required at least 3 AOMs for weight regain. Semaglutide (N = 21), topiramate (N = 14), and metformin (N = 12) were most prescribed. Median %TBWL for the cohort at the first, second, and third visit was 1.7, 5.0, and 6.5 respectively. Fourteen (52%) achieved 5%TBWL, 10 (37%) achieved 10%TBWL, and 4 (15%) achieved 15%TBWL with combination AOMs and supervised medical intervention. An unusually high prevalence of genetic obesity variants in PBSWR was found, warranting further research.

Advances in obesity pharmacotherapy; learning from metabolic surgery and beyond

Currently, metabolic surgery (MS) constitutes the most effective means for durable weight loss of clinically meaningful magnitude, type 2 diabetes remission and resolution of non-alcoholic steatohepatitis, as well as other obesity-related comorbidities. Accumulating evidence on the mechanisms through which MS exerts its actions has highlighted the altered secretion of hormonally active peptides of intestinal origin with biological actions crucial to energy metabolism as key drivers of MS clinical effects. The initial success of glucagon-like peptide-1 (GLP-1) receptor agonists regarding weight loss and metabolic amelioration have been followed by the development of unimolecular dual and triple polyagonists, additionally exploiting the effects of glucagon and/or glucose-dependent insulinotropic polypeptide (GIP) which achieves a magnitude of weight loss approximating that of common MS operations. Through the implementation of such therapies, the feasibility of a “medical bypass”, namely the replication of the clinical effects of MS through non-surgical interventions may be foreseeable in the near future. Apart from weight loss, this approach ought to be put to the test also regarding other clinical outcomes, such as liver steatosis and steatohepatitis, cardiovascular disease, and overall prognosis, on which MS has a robustly demonstrated impact. Besides, a medical bypass as an alternative, salvage, or combination strategy to MS may promote precision medicine in obesity therapeutics.

Roux-en-Y gastric bypass and sleeve gastrectomy as revisional bariatric procedures after adjustable gastric banding: a retrospective cohort study

IntroductionThe frequency of revisional bariatric surgery is increasing, but its effectiveness and safety are not yet fully established. The aim of our study was to compare short-term outcomes of primary (pRYGB and pSG) and revisional bariatric surgeries (rRYGB and rSG).MethodsWe performed a retrospective cohort study assessing all patients submitted to primary and revisional (after a failed AGB) RYGB and SG in 2019. Each patient was followed-up at 6 months and 12 months after surgery. We compared pRYGB vs. rRYGB, pSG vs. rSG and rRYGB vs. rSG on weight loss, surgical complications, and resolution of comorbidities.ResultsWe assessed 494 patients, of which 18.8% had undergone a revisional procedure. Higher weight loss at 6 and 12 months was observed in patients undergoing primary vs. revisional procedures. Patients submitted to rRYGB lost more weight than those with rSG (%EWL 12 months = 82.6% vs. 69.0%, p < 0.001). Regarding the resolution of obesity-related comorbidities, diabetes resolution was more frequent in pRYGB than rRYGB (54.2% vs. 25.0%; p = 0.038). Also, 41.7% of the patients who underwent rRYGB had dyslipidemia resolution vs. 0% from the rSG group (p = 0.035). Dyslipidemia resolution was also more common in pSG vs. rSG (68.6% vs. 0.0%; p = 0.001). No significant differences in surgical complications were found.ConclusionRevisional bariatric surgery is effective and safe treating obesity and related comorbidities after AGB. Primary procedures appear to be associated with better weight loss outcomes. Further prospective studies are needed to better understand the role of revisional bariatric surgery.

The timing of energy intake.

The aim of the paper is to review the current evidence on the impact of 'the timing of energy intake' on the risk of developing obesity and obesity-related metabolic diseases. The prevalence of obesity is currently increasing worldwide thus becoming a severe health burden for most countries. Indeed, obesity represents a risk factor for several non-communicable diseases such as cancer, type 2 diabetes, dyslipidaemia, CVD and overall mortality. In order to treat obesity, several pharmacological approaches have been developed and are indicated for subjects with obesity with a BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 and obesity-related comorbidities. For severe obesity (BMI ≥ 40 kg/m2), bariatric surgery represents a promising approach. The most common bariatric surgical procedures are represented by the Roux-en-Y gastric bypass, laparoscopic adjustable band, laparoscopic gastric sleeve and biliopancreatic diversion with duodenal switch. Both anti-obesity pharmacological and surgical treatments require change in lifestyle. When a nutritional plan is established, attention is usually paid to macronutrient composition and energy intake, while 'the time of food' is not taken into account. Chronotype, which is the attitude of a subject to carry out most of their daily activities in the first (morning chronotype) or second half (evening chronotype) of the day, has been reported to have a role in the pathogenesis of obesity and obesity-related cardiometabolic diseases as well as eating speed. Thus, adopting a physiological timing of energy intake could be an additional strategy to potentiate the current anti-obesity approaches.

Serum apelin-12 and obesity-related markers in Egyptian children with Down syndrome

Children with Down syndrome (DS) exhibit higher overweight/obesity rates than their typically developing peers. Apelin-12 is a bioactive adipokine that exerts vital roles in obesity-related cardiometabolic comorbidities. To date, apelin-12 has not been investigated in obese-DS. This study aimed to explore the possible association between serum apelin-12 and obesity-related markers and to evaluate the efficiency of apelin-12 in the prediction of metabolic syndrome (MetS) in obese-DS compared to BMI Z-score matched obese-control. The cross-sectional study included 150 prepubertal children classified into three groups; obese-DS (n = 50), obese-control (n = 50), and normal-weight-control (n = 50). Anthropometric parameters, body adiposity, fasting serum levels of blood glucose (FBG), insulin, lipid profile, and apelin-12 were evaluated. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from FBG and insulin. MetS was defined using Adult Treatment Panel III criteria modified for the pediatric age group. ROC curves were analyzed to evaluate the efficiency of apelin-12 in predicting MetS in obesity groups. Obese-DS exhibited higher body adiposity with marked central fat distribution, atherogenic lipid profile, and higher HOMA-IR compared to obese-control. Apelin-12 was significantly higher in obese-DS and obese-DS with MetS compared to obese-control and obese-control with MetS respectively (p < 0.001). The increase in apelin-12 with higher obesity grades was pronounced in obese-DS. Apelin-12 strongly correlated with body adiposity, several MetS risk factors, and HOMA-IR in obese-DS. Significantly higher AUC for apelin-12 in the diagnosis of MetS among obese-DS than obese-control (AUC = 0.948 vs. AUC = 0.807; p = 0.04).Conclusions: The current study supports the crucial role of apelin-12 in obesity-related clinical and biochemical markers and in MetS in obese-DS and obese-control. Serum apelin-12 is a potential diagnostic biomarker for MetS with greater performance in obese-DS than obese-control raising its potential for clinical and therapeutic applications.What is Known:• Obese-DS children displayed excess body adiposity, Pronounced central fat distribution, atherogenic lipid profile, higher HOMA-IR, and higher prevalence of MetS than obese-control.What is New:• Higher serum apelin-12 was observed in obese-DS and obese-DS with MetS than obese-control and obese-control with MetS respectively. The increase in apelin-12 level with increasing obesity grades was more pronounced in obese-DS.• Apelin-12 strongly correlated with obesity-related markers and MetS components in obese-DS. Apelin-12 performed better as a diagnostic biomarker for MetS in obese-DS than obese-control.

Inclusion of Subjects who are Obese in Drug Development: Current Status and Opportunities.

The prevalence of obesity has grown tremendously in recent years and this population has an increased risk of disease comorbidities. The presence of disease comorbidities requires treatment interventions and proper dosing guidelines. However, drug development programs often do not have adequate representation of individuals who are obese in clinical trials, leaving gaps in the understanding of treatment response leading to a lack of adequate individualization options. Based on a recent survey of approved drug product package inserts, very few approved products included specific dosing based on obesity, in both adults and pediatrics. Reasons for the limited information on patients who are obese may include the under-reporting of information regarding such patients and a lack of clinical trial diversity in enrolling patient groups in whom obesity or obesity-related comorbidities are more prevalent. An inadvertent impact of the practice of exclusion of subsets of patients with some comorbidities in clinical trials may play a role in the reduced enrollment of individuals who are obese. Recently, regulatory authorities have taken specific initiatives to promote clinical trial diversity, including engaging with stakeholders and publishing regulatory guidance. These guidance documents highlight the need to enroll diverse clinical trial populations and provide recommendations on concepts related to drug development for obese populations. Such efforts will help to address the gap in information regarding drug response and dosing in patients who are obese.

53 Change in Cerebral Metabolite Concentrations Following Bariatric Surgery

Objective:Obesity is associated with adverse effects on brain health, including increased risk for neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined change in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery.Participants and Methods:35 patients with obesity (BMI &gt; 35 kg/m2) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel 1H-proton magnetic resonance spectroscopy at baseline (pre-surgery) and within one year post-surgery. Spectra were obtained from a large medial frontal brain region. Tissue-corrected absolute concentrations for metabolites including choline-containing compounds (Cho), myo-inositol (mI), N-acetylaspartate (NAA), creatine (Cr), and glutamate and glutamine (Glx) were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycemic control.Results:Bariatric surgery was associated with a reduction in cerebral Cho (f[34j = -3.79, p &lt; 0.001, d = -0.64) and mI (f[34] = -2.81, p &lt; 0.01, d = -0.47) concentrations. There were no significant changes in NAA, Glx, or Cr concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p &lt; 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p &lt; 0.05).Conclusions:Participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

LGBTQ-competent obesity prevention and management.

Obesity is a complex and largely preventable disease that is an enormous burden to patient health and to the healthcare system. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) patients and their healthcare providers should be aware of their personal risks and causes of weight gain and obesity. Sensitive, comprehensive, and competent LGBTQ preventive care and treatment are needed to address the needs of this population, improve patient outcomes, and reduce healthcare inequalities. Research is needed to further evaluate the confluence of obesity and metabolic risk factors in LGBTQ patients, and to develop prevention and treatment strategies to reduce the risk for obesity-related comorbidities, chronic disease, and death.

Bariatric surgery provision in response to the COVID-19 pandemic: retrospective cohort study of a national registry.

When surgery resumed following the outbreak of the COVID-19 pandemic, guidelines recommended the prioritization of patients with greater obesity-related co-morbidities and/or higher body mass index. The aim of this study was to record the effect of the pandemic on total number, patient demographics, and perioperative outcomes of elective bariatric surgery patients in the United Kingdom. The United Kingdom National Bariatric Surgical Registry was used to identify patients who underwent elective bariatric surgery during the pandemic (1 yr from April 1, 2020). Characteristics of this group were compared with those of a pre-pandemic cohort. Primary outcomes were case volume, case mix, and providers. National Health Service cases were analyzed for baseline health status and perioperative outcomes. Fisher exact, χ2, and Student t tests were used as appropriate. The total number of cases decreased to one third of pre-pandemic volume (8615 to 2930). The decrease in operating volume varied, with 36 hospitals (45%) experiencing a 75%-100% reduction. Cases performed in the National Health Service fell from 74% to 53% (P < .0001). There was no change in baseline body mass index (45.2 ± 8.3 kg/m2 from 45.5 ± 8.3 kg/m2; P = .23) or prevalence of type 2 diabetes (26% from 26%; P = .99). Length of stay (median 2 d) and surgical complication rate (1.4% from 2.0%; relative risk = .71; 95% CI .45-1.12; P = .13) were unchanged. In the context of a dramatic reduction in elective bariatric surgery due to the COVID-19 pandemic, patients with more severe co-morbidities were not prioritized for surgery. These findings should inform preparation for future crises.

Impact of Bariatric Surgery on Patients' Satisfaction and Quality of Life: A Narrative Review

Context: Obesity is a significant health issue that has been considered an epidemic in the world during the last 20 years and has persistently increased over time. The World Health Organization recently reported that the worldwide prevalence of overweight among adults was more than 1.9 billion, and approximately 650 million adults were obese. Bariatric surgery remains the most successful and effective long-term option for treating morbid obesity and obesity-related co-morbidities due to the significant outcomes in long-term weight loss, resolution of obesity-related co-morbidities, reduction of cardiovascular complications, and the causes of obesity-related mortality.&#x0D; Aim: This review sought to provide a comprehensive and critical summary of existing literature on the impact of bariatric surgery on patients’ satisfaction and quality of life.&#x0D; Methods: A systematic search was undertaken between 2018 and 2022 with specific inclusion criteria. Search terms were determined to select the best relevant studies using a wide search in different databases, including PubMed, Medline, EBSCO, EBMR, and ERIC. The review used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify the literature used in this review. The review identified fifty studies that met the eligibility criteria and were involved in this review.&#x0D; Results: The result indicates that quality of life was improved in most of the studies after the different types of bariatric surgeries. Also, the satisfaction level was high in most of the retrieved studies. Besides, all co-morbidities associated with obesity were reduced significantly.&#x0D; Conclusion: The findings demonstrate that each surgical procedure has negative and positive outcomes. The finding also recognized the impact of bariatric surgery in improving the patients' satisfaction, enhancing their quality of life, and remission of obesity-related co-morbidity diseases. Bariatric surgery is strongly suggested in the treatment of morbidly obese patients.

Liver-Selective Imidazolopyrazine Mitochondrial Uncoupler SHD865 Reverses Adiposity and Glucose Intolerance in Mice.

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation. Herein, we report the in vitro and in vivo characterization of compound SHD865, the first compound to be studied in vivo in a newly discovered class of imidazolopyrazine mitochondrial uncouplers. SHD865 is a derivative of the furazanopyrazine uncoupler BAM15. SHD865 is a milder mitochondrial uncoupler than BAM15 that results in a lower maximal respiration rate. In a mouse model of diet-induced adiposity, six-week treatment with SHD865 completely restored normal body composition and glucose tolerance to levels like those of chow-fed controls without altering food intake. SHD865 treatment also corrected liver steatosis and plasma hyperlipidemia to normal levels comparable with chow-fed controls. SHD865 has maximal oral bioavailability in rats and slow clearance in human microsomes and hepatocytes. Collectively, these data identify the potential of imidazolopyrazine mitochondrial uncouplers as drug candidates for the treatment of obesity-related disorders.

Robotic-assisted Roux-en-Y gastric bypass with the novel platform HugoTM RAS: preliminary experience in 15 patients.

Robotic assisted surgery is a rapidly developing field in bariatric surgery. Its wide diffusion has led to the development and standardisation of robotic assisted approaches for various bariatric operations. However, further application has been limited thus far due to issues of cost-effectiveness and accessibility. The introduction of new robotic platforms may help overcome those obstacles. In this study, we present the first fifteen cases of Roux-en-Y Gastric Bypass (RYGB) operations performed with the new Hugo™ RAS system (Medtronic, Minneapolis, MN, USA). From January to March 2023, consecutive patients scheduled for minimal invasive Roux-en-Y-Bypass were randomly selected and underwent the procedure robotic-assisted with the new platform. No exclusion criteria were applied. Seven female and eight male patients with a median BMI of 42 (range: 36-50) and obesity-related comorbidities in eight cases underwent RYGB. The median docking time was 7min (range: 6-8.5) and the median console time was 100min (range: 70-150). Procedures were performed without intraoperative complications and no conversion to laparoscopy or open surgery was noted. Operative times were indicative of a steep learning curve. No early post-operative complications were observed. Based on our initial experience, RYGB with the Hugo™ RAS system is promising and may be integrated in established robotic programmes without requiring a long adaptation period.

Physical activity in the new era of antiobesity medications.

Contemporary antiobesity medications (AOMs) are highly efficacious for the treatment of obesity and obesity-related comorbidities. Given this effectiveness, lifestyle factors within the context of AOM treatments need to refocus and move away from efforts to enhance weight loss. Rather, lifestyle considerations should pivot to being complementary to the benefits realized with AOM treatment and be redirected to enhancing holistic patient health and well-being. Physical activity is an important lifestyle behavior that contributes to many health benefits both in conjunction with, and in the absence of, weight loss. Physical activity improves cardiorespiratory fitness, muscle strength, and physical function. Physical activity may attenuate the loss of lean mass that is observed with AOM treatments and may enhance the quality and function of muscle. Physical activity is a key behavior for holistic health within this era of contemporary AOMs that warrants appropriate attention within the clinical care of patients.

Weight loss induced alleviation of sleep-disordered breathing is associated with improvement of non-alcoholic fatty liver disease

IntroductionSleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD. MethodsObese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h. Results48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade. ConclusionPreexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.