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Introduction: Pathogenic heterozygous MC4R variants are associated with hyperphagia and variable degrees of obesity. Several research groups have reported short-term weight loss outcomes after bariatric surgery in a few patients with MC4R variants, but lack of longer-term data prevents evidence-based clinical decision-making., Materials and Methods: Bariatric surgery patients with heterozygous (likely) pathogenic MC4R variants, from three collaborating centers in the Netherlands, France, and the UK, were compared to matched controls (matched 2:1 for age, sex, preoperative BMI, surgical procedure, and diabetes mellitus, but without MC4R mutations). Weight loss and regain outcomes up to 6 years of follow-up were compared., Results: At 60 months of follow-up after RYGB, cases with MC4R variants showed weight regain with a mean of 12.8% (± 10.4 SD) total weight loss (TWL) from nadir, compared to 7.9% (± 10.5 SD) in the controls (p = 0.062). Among patients receiving SG, the cases with MC4R variants experienced inferior weight loss (22.6% TWL) during the first year of follow-up compared to the controls (29.9% TWL) (p = 0.010)., Conclusions: This multicenter study reveals inferior mid-term weight outcomes of cases with MC4R variants after SG, compared to RYGB. Since adequate weight loss outcomes were observed after RYGB, this procedure would appear to be an appropriate surgical approach for this group. However, the pattern of weight regain seen in cases with MC4R variants after both RYGB and SG highlights the need for pro-active lifelong management to prevent relapse, as well as careful expectation management., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Micronutrient deficiencies are frequently reported after sleeve gastrectomy (SG), and therefore lifelong daily multivitamin supplementation is highly recommended. Based on literature and the results of a previous randomized controlled trial, a specialized multivitamin supplement for SG patients was further optimized (WLS Optimum 2.0, FitForMe). The present study reports on its short-term effectiveness., Materials and Methods: An open-label study was performed in which 76 patients were included to receive WLS Optimum 2.0 for 12 months (Opt 2.0 group). This group was compared with a group of 75 patients that had received WLS Optimum 1.0 for 12 months during a previous study (Opt 1.0 group)., Results: Intention-to-treat analysis (Opt 1.0, n = 69; Opt 2.0, n = 75) showed higher serum levels of vitamin B12, vitamin B6, and zinc, and a lower prevalence of deficiencies for vitamin B12 and phosphate in the Opt 2.0 group. MCV and serum folic acid levels were higher in the Opt 1.0 group. Over the 12-month study period, mean increase in serum levels of phosphate, vitamin B6, and zinc was higher in the Opt 2.0 group, and MCV and serum vitamin D levels increased more in the Opt 1.0 group., Conclusion: The present study showed that the use of a specialized multivitamin supplement for SG patients is effective at preventing deficiencies for most vitamins and minerals, specifically in compliant patients. However, a strict follow-up regime remains necessary to monitor nutritional status and to improve patient compliance.

Purpose of Review: The global prevalence of obesity has increased rapidly over the last decades, posing a severe threat to human health. Currently, bariatric surgery is the most effective therapy for patients with morbid obesity. It is unknown whether this treatment is also suitable for patients with obesity due to a confirmed genetic defect (genetic obesity disorders). Therefore, this review aims to elucidate the role of bariatric surgery in the treatment of genetic obesity., Recent Findings: In monogenic non-syndromic obesity, an underlying genetic defect seems to be the most important factor determining the efficacy of bariatric surgery. In syndromic obesity, bariatric surgery result data are scarce, and even though some promising follow-up results have been reported, caution is required as patients with more severe behavioral and developmental disorders might have poorer outcomes. There is limited evidence in support of bariatric surgery as a treatment option for genetic obesity disorders; hence, no strong statements can be made regarding the efficacy and safety of these procedures for these patients. However, considering that patients with genetic obesity often present with life-threatening obesity-related comorbidities, we believe that bariatric surgery could be considered a last-resort treatment option in selected patients.

Background: Mutations in the leptin-melanocortin pathway genes are known to cause monogenic obesity. The prevalence of these gene mutations and their effect on weight loss response after bariatric surgery are still largely unknown., Objective: To determine the prevalence of genetic obesity in a large bariatric cohort and evaluate their response to bariatric surgery., Methods: Mutation analysis of 52 obesity-associated genes. Patient inclusion criteria were a BMI > 50 kg/m 2 , an indication for revisional surgery or an early onset of obesity (< 10 years of age)., Results: A total of 1014 patients were included, of whom 30 (3%) were diagnosed with genetic obesity, caused by pathogenic heterozygous mutations in either MC4R, POMC, PCSK1, SIM1, or PTEN. The percentage total body weight loss (%TBWL) after Roux-en-Y gastric bypass (RYGB) surgery was not significantly different for patients with a mutation in MC4R, POMC, and PCSK1 compared with patients lacking a molecular diagnosis. Of the confirmed genetic obesity cases, only patients with MC4R mutations receiving a sleeve gastrectomy (SG) showed significantly lower %TBWL compared with patients lacking a molecular diagnosis, during 2 years of follow-up., Conclusions: In this cohort of morbid obese bariatric patients, an estimated prevalence of monogenic obesity of 3% is reported. Among these patients, the clinical effects of heterozygous mutations in POMC and PCSK1 do not interfere with the effectiveness of most commonly performed bariatric procedures within the first 2 years of follow-up. Patients with MC4R mutations achieved superior weight loss after primary RYGB compared with SG.

Background: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device designed to induce weight loss and improve glycemic control. The liner is licensed for a maximum implant duration of 12 months. It might be hypothesized that extension of the dwelling time results in added value. The goals of our study were to determine weight change, change in glycemic control, and safety in patients with an intended 24 months of DJBL dwelling time., Methods: Patients were initially selected for a 12-month implantation period. When no physical complaints or adverse events (AEs) occurred, motivated patients who responded well were selected for extension of dwelling time to 24 months. Patients underwent a control endoscopy 12 months after implantation and visited the out-patient clinic every 3 months up to explantation. Patients agreed to remove the DJBL when complaints or AEs occurred that could not be treated conservatively., Results: Implantation was extended in 44 patients, and 24 (55%) patients completed the full 24 months. Twenty patients required early removal due to AEs. During dwelling time, body weight decreased significantly (15.9 kg; TBWL 14.6%). HbA1c decreased non-significantly (4.9 mmol/mol). The number of insulin users and daily dose of insulin both decreased significantly. At 24 months after removal, glycemic control had worsened, while body weight was still significantly lower compared to baseline. In total, 68% of the patients experienced at least one AE. Two patients developed a hepatic abscess., Conclusions: DJBL treatment results in significant weight loss and improves glycemic control during implantation. The largest beneficial effects occur during the first 9-12 months after implantation. Extension of dwelling time to 24 months results only in stabilization of body weight and glycemic control. After explantation, weight improvements are maintained, but glycemic control worsens. As the cumulative risk of AEs increases with time, a maximal dwelling time of 12 months is advisable.

Background: Pathogenic PTEN gene mutations are known to cause PTEN tumor hamartoma syndrome. Recent studies also suggest a role for PTEN mutations in the pathogenesis of obesity. No PTEN mutations have been reported among bariatric surgery patients and obesity treatment results are unknown. Since preventive screening for associated tumors is offered to patients with molecular proven PTEN hamartoma tumor syndrome, recognition of this condition in the bariatric surgery clinic is important., Method: We present a patient with morbid obesity who carries a known pathogenic PTEN mutation, identified at the bariatric surgery clinic using an obesity gene panel consisting of 52 obesity-associated genes. We analyzed the weight loss response during the first 3 years after Sleeve Gastrectomy., Results: At 1, 2 and 3 years after surgery, the patient achieved a Total Body Weight Loss of 39.4%, 48.8% and 44.9%, respectively. This corresponds to the results of a control group of 18 female patients with normal genetic test results., Conclusion: Our patient illustrates the importance of recognizing this serious genetic condition for which preventive cancer screening options are available. The positive weight loss results after Sleeve Gastrectomy suggest that this could be a successful treatment option for obesity patients with PTEN mutations., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Introduction: One of the current criteria for bariatric surgery is to be of an age between 18 and 65 years. In all the available literature, there is a lack of studies focusing on the results of bariatric surgery in younger patient. This could be of great interest because the weight loss response can be altered by differences in metabolism or compliance rate. In recent years, a high amount of patients between 18 and 25 years of age have undergone bariatric surgery in our center, and it is our aim to evaluate the weight loss results in this youngest patient group., Methods: All preoperative and perioperative data from patients aged 18-25 and 35-55 years (control group) were collected retrospectively. Bariatric procedures took place between 2011 and 2014. Follow-up data were gathered prospectively by collecting (laboratory) measurements and questionnaires., Results: In total, 103 young adults (mean age 22.5) were matched to 103 adult control patients (mean age 42.6) on BMI and date of surgery. Of the young adults' group, 75 patients underwent a Roux-en-Y gastric bypass (RYGB) compared with 80 patients in the control group. Three years after RYGB, mean %total body weight loss (%TBWL) was 34 (± 9) and 30.3 (± 9) (p = 0.03), respectively., Conclusion: Bariatric surgery is effective in young adults, and results after RYGB are even better compared with age groups in which bariatric surgery is most often performed. The high remission rate of comorbidities shows the importance of effective treatment options at a young age and preventing damaging effects in the long term.

Body fat mass increases when energy intake exceeds energy expenditure. In the long term, a positive energy balance will result in obesity. The worldwide prevalence of obesity has increased dramatically, posing a serious threat to human health. Therefore, insight in the pathogenesis of obesity is important to identify novel prevention and treatment strategies. This review describes the physiology of energy expenditure and energy intake in the context of body weight gain in humans. We focus on the components of energy expenditure and the regulation of energy intake. Finally, we describe rare monogenetic causes leading to an impairment in central regulation of food intake and obesity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Obesity is a global and severe health problem. Due to genetic heterogeneity, the identification of genetic defects in patients with obesity can be time consuming and costly. Therefore, we developed a custom diagnostic targeted next-generation sequencing (NGS)-based analysis to simultaneously identify mutations in 52 obesity-related genes. The aim of this study was to assess the diagnostic yield of this approach in patients with suspected genetic obesity., Methods: DNA of 1230 patients with obesity (median BMI adults 43.6 kg/m 2 ; median body mass index-SD children +3.4 SD) was analysed in the genome diagnostics section of the Department of Genetics of the UMC Utrecht (The Netherlands) by targeted analysis of 52 obesity-related genes., Results: In 48 patients pathogenic mutations confirming the clinical diagnosis were detected. The majority of these were observed in the MC4R gene (18/48). In an additional 67 patients a probable pathogenic mutation was identified, necessitating further analysis to confirm the clinical relevance., Conclusions: NGS-based gene panel analysis in patients with obesity led to a definitive diagnosis of a genetic obesity disorder in 3.9% of obese probands, and a possible diagnosis in an additional 5.4% of obese probands. The highest yield was achieved in a selected paediatric subgroup, establishing a definitive diagnosis in 12 out of 164 children with severe early onset obesity (7.3%). These findings give a realistic insight in the diagnostic yield of genetic testing for patients with obesity and could help these patients to receive (future) personalised treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: After Roux-en-Y gastric bypass (RYGB), approximately 10% of patients have insufficient weight loss (excess body mass index loss<50%). Gastric pouch emptying may have a role in weight loss., Objectives: To compare pouch emptying of patients with poor weight loss and patients with successful weight loss after RYGB., Setting: A research-intensive nonacademic hospital and center of expertise in bariatric surgery in the Netherlands METHODS: Female patients were included from among patients with the least (poor weight loss group [P-WL]) and the most weight loss (successful weight loss group [S-WL]) in our center 2 years after RYGB. Pouch emptying scintigraphy was performed after ingestion of a radiolabeled solid meal. Emptying curves, intestinal content (IC) at meal completion and after 15, 30, 45, and 60 minutes, half emptying time, and maximal pouch emptying rate were compared., Results: Five individuals were included in P-WL and 5 in S-WL, on average 2.5 ± .3 years after RYGB. Total weight loss was 18 ± 4.1% in P-WL and 44 ± 5.7% in S-WL (P<.001). In P-WL, a fast initial pouch emptying and exponential emptying curve was observed, compared with a slower initial emptying and more linear curve in S-WL. Faster emptying in P-WL was also shown by a larger IC meal (42 ± 18% versus 4.0 ± 3.3%,), IC 15 (76 ± 15% versus 35 ± 22%), and IC 30 (85 ± 12% versus 54 ± 25%), and a greater maximal pouch emptying rate (17 ± 4.7 versus 5.6 ± 3.4%/min) compared with S-WL (P<.05). A linear correlation was found between total weight loss and maximal pouch emptying rate (Pearson R = .82, P = .004)., Conclusions: Pouch emptying for solid food was faster in patients with the least weight loss compared with patients with the most weight loss after RYGB. If pouch emptying is an important mechanism in weight loss, altering the pouch outlet may improve poor weight loss management., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)