{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:44:47Z","timestamp":1791326687634,"version":"4.3.1"},"reference-count":46,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":254,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dr. Horber Adipositas Stiftung"},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["GEPIDIAB-294785"],"award-info":[{"award-number":["GEPIDIAB-294785"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,8,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Data on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Between 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>At baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Sequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc16-0115","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T00:29:09Z","timestamp":1464136149000},"page":"1384-1392","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":51,"title":["Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (<i>MC4R<\/i>) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study"],"prefix":"10.2337","volume":"39","author":[{"given":"Am\u00e9lie","family":"Bonnefond","sequence":"first","affiliation":[{"name":"CNRS UMR 8199, Lille Pasteur Institute, Lille, France"},{"name":"Lille University, Lille, France"},{"name":"European Genome Institute for Diabetes, FR 3508, Lille, France"},{"name":"Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, Imperial College London, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramsi","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein"},{"name":"Dr. Horber Adipositas Stiftung, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Meyre","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Stutzmann","sequence":"additional","affiliation":[{"name":"CNRS UMR 8199, Lille Pasteur Institute, Lille, France"},{"name":"Lille University, Lille, France"},{"name":"European Genome Institute for Diabetes, FR 3508, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doroth\u00e9e","family":"Thuillier","sequence":"additional","affiliation":[{"name":"CNRS UMR 8199, Lille Pasteur Institute, Lille, France"},{"name":"Lille University, Lille, France"},{"name":"European Genome Institute for Diabetes, FR 3508, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitre G.","family":"Stefanov","sequence":"additional","affiliation":[{"name":"Scientific Computing Center and Departments of Surgery, Medicine, and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Froguel","sequence":"additional","affiliation":[{"name":"CNRS UMR 8199, Lille Pasteur Institute, Lille, France"},{"name":"Lille University, Lille, France"},{"name":"European Genome Institute for Diabetes, FR 3508, Lille, France"},{"name":"Department of Genomics of Common Disease, School of Public Health, Hammersmith Hospital, Imperial College London, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz F.","family":"Horber","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Landesspital Liechtenstein, Vaduz, Liechtenstein"},{"name":"Dr. Horber Adipositas Stiftung, Zurich, Switzerland"},{"name":"University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Kral","sequence":"additional","affiliation":[{"name":"Scientific Computing Center and Departments of Surgery, Medicine, and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2016,5,23]]},"reference":[{"key":"2022031301025373000_B1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1056\/NEJMoa066254","article-title":"Effects of bariatric surgery on mortality in Swedish obese subjects","volume":"357","author":"Sj\u00f6str\u00f6m","year":"2007","journal-title":"N Engl J Med"},{"key":"2022031301025373000_B2","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1001\/2012.jama.11164","article-title":"Health benefits of gastric bypass surgery after 6 years","volume":"308","author":"Adams","year":"2012","journal-title":"JAMA"},{"key":"2022031301025373000_B3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.maturitas.2013.12.004","article-title":"Diabesity: palliating, curing or preventing the dysmetabolic diathesis","volume":"77","author":"Kral","year":"2014","journal-title":"Maturitas"},{"key":"2022031301025373000_B4","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1056\/NEJMoa0901836","article-title":"Perioperative safety in the longitudinal assessment of bariatric surgery","volume":"361","author":"Flum","year":"2009","journal-title":"N Engl J Med"},{"key":"2022031301025373000_B5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jamasurg.2013.3654","article-title":"The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012","volume":"149","author":"Chang","year":"2014","journal-title":"JAMA Surg"},{"key":"2022031301025373000_B6","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1007\/s00464-007-9536-x","article-title":"Reoperative bariatric surgery","volume":"21","author":"Sarr","year":"2007","journal-title":"Surg Endosc"},{"key":"2022031301025373000_B7","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.soard.2007.10.004","article-title":"Revisional bariatric surgery for failed restrictive procedures","volume":"4","author":"Coakley","year":"2008","journal-title":"Surg Obes Relat Dis"},{"key":"2022031301025373000_B8","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1056\/NEJMoa021971","article-title":"Binge eating as a major phenotype of melanocortin 4 receptor gene mutations","volume":"348","author":"Branson","year":"2003","journal-title":"N Engl J Med"},{"key":"2022031301025373000_B9","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1056\/NEJMoa022050","article-title":"Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene","volume":"348","author":"Farooqi","year":"2003","journal-title":"N Engl J Med"},{"key":"2022031301025373000_B10"},{"key":"2022031301025373000_B11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1381\/096089206775565113","article-title":"Melanocortin-4 receptor gene and complications after gastric banding","volume":"16","author":"Peterli","year":"2006","journal-title":"Obes Surg"},{"issue":"2","key":"2022031301025373000_B12","first-page":"7","article-title":"Influence of obesity-susceptibility loci (MC4R and INSIG2) on the outcome of weight loss and amelioration of co-morbidity in obese patients treated by a gastric-bypass","author":"Goergen","year":"2011","journal-title":"Bull Soc Sci Med Grand Duche Luxemb"},{"key":"2022031301025373000_B13","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1007\/s11695-010-0295-8","article-title":"Weight loss after Roux-en-Y gastric bypass in obese patients heterozygous for MC4R mutations","volume":"21","author":"Aslan","year":"2011","journal-title":"Obes Surg"},{"key":"2022031301025373000_B14"},{"key":"2022031301025373000_B15","doi-asserted-by":"crossref","first-page":"E1630","DOI":"10.1210\/jc.2011-1130","article-title":"Heritability of the weight loss response to gastric bypass surgery","volume":"96","author":"Hatoum","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031301025373000_B16","doi-asserted-by":"crossref","first-page":"e48221","DOI":"10.1371\/journal.pone.0048221","article-title":"Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery","volume":"7","author":"Valette","year":"2012","journal-title":"PLoS One"},{"key":"2022031301025373000_B17","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/oby.20511","article-title":"Weight loss after bariatric surgery in morbidly obese adolescents with MC4R mutations","volume":"22","author":"Censani","year":"2014","journal-title":"Obesity (Silver Spring)"},{"key":"2022031301025373000_B18","doi-asserted-by":"crossref","first-page":"e93629","DOI":"10.1371\/journal.pone.0093629","article-title":"Long-term weight-loss in gastric bypass patients carrying melanocortin 4 receptor variants","volume":"9","author":"Moore","year":"2014","journal-title":"PLoS One"},{"key":"2022031301025373000_B19","doi-asserted-by":"crossref","first-page":"e93324","DOI":"10.1371\/journal.pone.0093324","article-title":"Comment on: Valette et al. Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery. PLOS ONE 2012; 7(11):E48221","volume":"9","author":"Meyre","year":"2014","journal-title":"PLoS One"},{"key":"2022031301025373000_B20","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/sj.mp.4001491","article-title":"Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations","volume":"9","author":"Hebebrand","year":"2004","journal-title":"Mol Psychiatry"},{"key":"2022031301025373000_B21","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1210\/jc.2005-1411","article-title":"Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating","volume":"91","author":"Lubrano-Berthelier","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031301025373000_B22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11695-008-9675-8","article-title":"Successful multi-intervention treatment of severe obesity: a 7-year prospective study with 96% follow-up","volume":"19","author":"Steffen","year":"2009","journal-title":"Obes Surg"},{"key":"2022031301025373000_B23","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1381\/096089203765887813","article-title":"Laparoscopic adjustable gastric banding with duodenal switch for morbid obesity: technique and preliminary results","volume":"13","author":"Gagner","year":"2003","journal-title":"Obes Surg"},{"key":"2022031301025373000_B24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.surg.2004.06.007","article-title":"Management of failed adjustable gastric banding","volume":"137","author":"Biertho","year":"2005","journal-title":"Surgery"},{"key":"2022031301025373000_B25","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/(SICI)1098-108X(199911)26:3<231::AID-EAT1>3.0.CO;2-6","article-title":"Imipramine and diet counseling with psychological support in the treatment of obese binge eaters: a randomized, placebo-controlled double-blind study","volume":"26","author":"Laederach-Hofmann","year":"1999","journal-title":"Int J Eat Disord"},{"key":"2022031301025373000_B26","unstructured":"American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Available from http:\/\/psychiatryonline.org\/doi\/book\/10.1176\/appi.books.9780890425596. Accessed 6 July 2015"},{"key":"2022031301025373000_B27","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.jneb.2010.02.015","article-title":"Under- and over-reporting of energy intake in Slovenian adolescents","volume":"44","author":"Kobe","year":"2012","journal-title":"J Nutr Educ Behav"},{"key":"2022031301025373000_B28"},{"key":"2022031301025373000_B29","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/oby.2007.99","article-title":"Loss of control is central to psychological disturbance associated with binge eating disorder","volume":"16","author":"Colles","year":"2008","journal-title":"Obesity (Silver Spring)"},{"key":"2022031301025373000_B30","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.2337\/db08-0153","article-title":"Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees","volume":"57","author":"Stutzmann","year":"2008","journal-title":"Diabetes"},{"key":"2022031301025373000_B31","doi-asserted-by":"crossref","first-page":"e26953","DOI":"10.1371\/journal.pone.0026953","article-title":"Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population","volume":"6","author":"Wang","year":"2011","journal-title":"PLoS One"},{"key":"2022031301025373000_B32","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1021\/bi0600300","article-title":"Pharmacological characterization of 40 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists and the agouti-related protein (AGRP) antagonist","volume":"45","author":"Xiang","year":"2006","journal-title":"Biochemistry"},{"key":"2022031301025373000_B33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.gene.2010.03.001","article-title":"Functional analysis of melanocortin-4-receptor mutants identified in severely obese subjects living in Southern Italy","volume":"457","author":"Alfieri","year":"2010","journal-title":"Gene"},{"key":"2022031301025373000_B34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1471-2350-10-25","article-title":"Prevalence of pathogenetic MC4R mutations in Italian children with early onset obesity, tall stature and familial history of obesity","volume":"10","author":"Santoro","year":"2009","journal-title":"BMC Med Genet"},{"key":"2022031301025373000_B35","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"2022031301025373000_B36","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1056\/NEJM200308073490615","article-title":"Binge eating as a phenotype of melanocortin 4 receptor gene mutations (Letter)","volume":"349","author":"Gotoda","year":"2003","journal-title":"N Engl J Med"},{"key":"2022031301025373000_B37","doi-asserted-by":"crossref","first-page":"E2101","DOI":"10.1210\/jc.2014-1651","article-title":"Obesity-associated melanocortin-4 receptor mutations are associated with changes in the brain response to food cues","volume":"99","author":"van der Klaauw","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031301025373000_B38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1056\/NEJMoa0803085","article-title":"Modulation of blood pressure by central melanocortinergic pathways","volume":"360","author":"Greenfield","year":"2009","journal-title":"N Engl J Med"},{"key":"2022031301025373000_B39","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1210\/jc.2009-2297","article-title":"Sympathetic function in human carriers of melanocortin-4 receptor gene mutations","volume":"95","author":"Sayk","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031301025373000_B40","doi-asserted-by":"crossref","first-page":"R695","DOI":"10.1152\/ajpregu.2000.279.2.R695","article-title":"Effect of intracerebroventricular alpha-MSH on food intake, adiposity, c-Fos induction, and neuropeptide expression","volume":"279","author":"McMinn","year":"2000","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2022031301025373000_B41","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1126\/science.100883","article-title":"Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone","volume":"202","author":"Belchetz","year":"1978","journal-title":"Science"},{"key":"2022031301025373000_B42","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1093\/ajcn\/88.3.797","article-title":"Association of the melanocortin-4 receptor V103I polymorphism with dietary intake in severely obese persons","volume":"88","author":"Pichler","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"2022031301025373000_B43","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1136\/jmg.2004.018614","article-title":"Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index","volume":"41","author":"Dempfle","year":"2004","journal-title":"J Med Genet"},{"key":"2022031301025373000_B44","doi-asserted-by":"crossref","first-page":"R1215","DOI":"10.1152\/ajpregu.00446.2012","article-title":"Sex differences in the physiology of eating","volume":"305","author":"Asarian","year":"2013","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"2022031301025373000_B45"},{"key":"2022031301025373000_B46","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1172\/JCI76305","article-title":"Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms","volume":"125","author":"Manning","year":"2015","journal-title":"J Clin Invest"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/care.diabetesjournals.org\/syndication\/doi\/10.2337\/dc16-0115","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/39\/8\/1384\/626259\/dc160115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/39\/8\/1384\/626259\/dc160115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T04:38:30Z","timestamp":1647146310000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/39\/8\/1384\/37120\/Eating-Behavior-Low-Frequency-Functional-Mutations"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,23]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2016,5,23]]},"published-print":{"date-parts":[[2016,8,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc16-0115","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,23]]}}}