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      Association of bariatric surgery with all-cause mortality and incidence of obesity-related disease at a population level: A systematic review and meta-analysis

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          Abstract

          Background

          Previous clinical trials and institutional studies have demonstrated that surgery for the treatment of obesity (termed bariatric or metabolic surgery) reduces all-cause mortality and the development of obesity-related diseases such as type 2 diabetes mellitus (T2DM), hypertension, and dyslipidaemia. The current study analysed large-scale population studies to assess the association of bariatric surgery with long-term mortality and incidence of new-onset obesity-related disease at a national level.

          Methods and findings

          A systematic literature search of Medline (via PubMed), Embase, and Web of Science was performed. Articles were included if they were national or regional administrative database cohort studies reporting comparative risk of long-term mortality or incident obesity-related diseases for patients who have undergone any form of bariatric surgery compared with an appropriate control group with a minimum follow-up period of 18 months. Meta-analysis of hazard ratios (HRs) was performed for mortality risk, and pooled odds ratios (PORs) were calculated for discrete variables relating to incident disease. Eighteen studies were identified as suitable for inclusion. There were 1,539,904 patients included in the analysis, with 269,818 receiving bariatric surgery and 1,270,086 control patients. Bariatric surgery was associated with a reduced rate of all-cause mortality (POR 0.62, 95% CI 0.55 to 0.69, p < 0.001) and cardiovascular mortality (POR 0.50, 95% CI 0.35 to 0.71, p < 0.001). Bariatric surgery was strongly associated with reduced incidence of T2DM (POR 0.39, 95% CI 0.18 to 0.83, p = 0.010), hypertension (POR 0.36, 95% CI 0.32 to 0.40, p < 0.001), dyslipidaemia (POR 0.33, 95% CI 0.14 to 0.80, p = 0.010), and ischemic heart disease (POR 0.46, 95% CI 0.29 to 0.73, p = 0.001). Limitations of the study include that it was not possible to account for unmeasured variables, which may not have been equally distributed between patient groups given the non-randomised design of the studies included. There was also heterogeneity between studies in the nature of the control group utilised, and potential adverse outcomes related to bariatric surgery were not specifically examined due to a lack of available data.

          Conclusions

          This pooled analysis suggests that bariatric surgery is associated with reduced long-term all-cause mortality and incidence of obesity-related disease in patients with obesity for the whole operated population. The results suggest that broader access to bariatric surgery for people with obesity may reduce the long-term sequelae of this disease and provide population-level benefits.

          Author summary

          Why was this study done?
          • Surgical treatment for obesity (known as bariatric or metabolic surgery) has been suggested to reduce risk of death in people with obesity and decrease development of other medical conditions including diabetes, heart disease, and certain forms of cancer.

          • This study aimed to analyse pooled data from previously published studies utilising data from national or regional administrative databases in order to examine the effect of bariatric surgery at a population level.

          What did the researchers do and find?
          • This study pooled data from published research articles utilising large administrative databases (with information from over 1.5 million patients)

          • The results suggested that bariatric surgery was associated with reduced risk of death, and decreased incidence of new-onset diabetes, high blood pressure, high cholesterol, and heart disease.

          What do these findings mean?
          • These findings suggest that bariatric surgery is associated with reduced risk of premature death or developing other medical conditions in people with obesity at a population level.

          • Increased availability of bariatric surgery may help to improve health outcomes for these individuals.

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          Most cited references40

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          Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women.

          Accumulating evidence indicates that abdominal adiposity is positively related to cardiovascular disease (CVD) risk and some other diseases independently of overall adiposity. However, the association of premature death resulting from these diseases with abdominal adiposity has not been widely studied, and findings are inconsistent. In a prospective cohort study of 44,636 women in the Nurses' Health Study, associations of abdominal adiposity with all-cause and cause-specific mortality were examined. During 16 years of follow-up, 3507 deaths were identified, including 751 cardiovascular deaths and 1748 cancer deaths. After adjustment for body mass index and potential confounders, the relative risks across the lowest to the highest waist circumference quintiles were 1.00, 1.11, 1.17, 1.31, and 1.79 (95% confidence interval [CI], 1.47 to 1.98) for all-cause mortality; 1.00, 1.04, 1.04, 1.28, and 1.99 (95% CI, 1.44 to 2.73) for CVD mortality; and 1.00, 1.18, 1.20, 1.34, and 1.63 (95% CI, 1.32 to 2.01) for cancer mortality (all P or = 88 cm was 3.02 (95% CI, 1.31 to 6.99) and for waist-to-hip ratio > 0.88 was 3.45 (95% CI, 2.02 to 6.92). After adjustment for waist circumference, hip circumference was significantly and inversely associated with CVD mortality. Anthropometric measures of abdominal adiposity were strongly and positively associated with all-cause, CVD, and cancer mortality independently of body mass index. Elevated waist circumference was associated with significantly increased CVD mortality even among normal-weight women.
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            Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial.

            Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years). Bariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.
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              Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study

              This multicenter longitudinal study examines long-term weight change and health status following Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding. Question What are the 7-year weight and comorbid health changes following Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding? Findings In this multicenter longitudinal study, 7-year mean weight loss was 28.4% with weight regain after 3 years of 3.9% for Roux-en-Y gastric bypass and 14.9% with 1.4% weight regain for laparoscopic adjustable gastric banding. The prevalence of dyslipidemia was reduced 7 years following both procedures, and diabetes and hypertension prevalence were reduced following gastric bypass; remission of diabetes at 7 years was 60.2% for Roux-en-Y gastric bypass and 20.3% for laparoscopic adjustable gastric banding. Meaning Most participants maintained much of their weight loss with variable fluctuations over the longer term, and comorbid health improvements were sustained after Roux-en-Y gastric bypass. Importance More information is needed about the durability of weight loss and health improvements after bariatric surgical procedures. Objective To examine long-term weight change and health status following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB). Design, Setting, and Participants The Longitudinal Assessment of Bariatric Surgery (LABS) study is a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers. Adults undergoing bariatric surgical procedures as part of clinical care between 2006 and 2009 were recruited and followed up until January 31, 2015. Participants completed presurgery, 6-month, and annual research assessments for up to 7 years. Main Outcome and Measures Percentage of weight change from baseline, diabetes, dyslipidemia, and hypertension, determined by physical measures, laboratory testing, and medication use. Results Of 2348 participants, 1738 underwent RYGB (74%) and 610 underwent LAGB (26%). For RYBG, the median age was 45 years (range, 19-75 years), the median body mass index (calculated as weight in kilograms divided by height in meters squared) was 47 (range, 34-81), 1389 participants (80%) were women, and 257 participants (15%) were nonwhite. For LAGB, the median age was 48 years (range, 18-78), the body mass index was 44 (range, 33-87), 465 participants (76%) were women, and 63 participants (10%) were nonwhite. Follow-up weights were obtained in 1300 of 1569 (83%) eligible for a year-7 visit. Seven years following RYGB, mean weight loss was 38.2 kg (95% CI, 36.9-39.5), or 28.4% (95% CI, 27.6-29.2) of baseline weight; between years 3 and 7 mean weight regain was 3.9% (95% CI, 3.4-4.4) of baseline weight. Seven years after LAGB, mean weight loss was 18.8 kg (95% CI, 16.3-21.3) or 14.9% (95% CI, 13.1-16.7), with 1.4% (95% CI, 0.4-2.4) regain. Six distinct weight change trajectory patterns for RYGB and 7 for LAGB were identified. Most participants followed trajectories in which weight regain from 3 to 7 years was small relative to year-3 weight loss, but patterns were variable. Compared with baseline, dyslipidemia prevalence was lower 7 years following both procedures; diabetes and hypertension prevalence were lower following RYGB only. Among those with diabetes at baseline (488 of 1723 with RYGB [28%]; 175 of 604 with LAGB [29%]), the proportion in remission at 1, 3, 5, and 7 years were 71.2% (95% CI, 67.0-75.4), 69.4% (95% CI, 65.0-73.8), 64.6% (95% CI, 60.0-69.2), and 60.2% (95% CI, 54.7-65.6), respectively, for RYGB and 30.7% (95% CI, 22.8-38.7), 29.3% (95% CI, 21.6-37.1), 29.2% (95% CI, 21.0-37.4), and 20.3% (95% CI, 9.7-30.9) for LAGB. The incidence of diabetes at all follow-up assessments was less than 1.5% for RYGB. Bariatric reoperations occurred in 14 RYGB and 160 LAGB participants. Conclusions and Relevance Following bariatric surgery, different weight loss patterns were observed, but most participants maintained much of their weight loss with variable fluctuations over the long term. There was some decline in diabetes remission over time, but the incidence of new cases is low following RYGB. Trial Registration clinicaltrials.gov Identifier: NCT00465829
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: InvestigationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                28 July 2020
                July 2020
                : 17
                : 7
                : e1003206
                Affiliations
                [1 ] Department of Surgery and Cancer, Imperial College London, London, United Kingdom
                [2 ] Department of Bariatric Surgery, Musgrove Park Hospital, Taunton, United Kingdom
                [3 ] Department of Molecular Medicine & Surgery, Karolinska Institutet, Stockholm, Sweden
                Chinese University of Hong Kong, CHINA
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7552-2266
                http://orcid.org/0000-0002-8349-4688
                Article
                PMEDICINE-D-20-00372
                10.1371/journal.pmed.1003206
                7386646
                32722673
                a8b8046e-79e0-402a-ab22-1c7e9d0aa3c9
                © 2020 Wiggins et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 February 2020
                : 22 June 2020
                Page count
                Figures: 4, Tables: 3, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100013342, NIHR Imperial Biomedical Research Centre;
                Award ID: NIHR-IAT-EAN/021/00146/C
                Award Recipient :
                SRM - National Institute of Health Research (NIHR) Imperial Biomedical Research Centre grant (Grant number NIHR-IAT-EAN/021/00146/C). Sponsors played no role in study design, data collection or analysis, decision to publish or manuscript preparation.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Digestive System Procedures
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Death Rates
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Body Mass Index
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Vascular Surgery
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                All relevant data are available within the manuscript and its Supporting information files.

                Medicine
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