Adolescent severe obesity is a prevalent, chronic, and serious disease with few effective and safe treatment options. To address this issue, a National Institutes of Health-sponsored workshop entitled “Developing Precision Medicine Approaches to the Treatment of Severe Obesity in Adolescents,” was convened, bringing together a multidisciplinary group of experts to review the current state of the science and identify (1) what is known regarding the epidemiology and biopsychosocial determinants of severe obesity in adolescents, (2) what is known regarding effectiveness of treatments for severe obesity in adolescents and predictors of response, and (3) gaps and opportunities for future research to develop more effective and targeted treatments for adolescents with severe obesity. Major topical areas discussed at the workshop included: appropriate BMI metrics, valid measures of phenotypes and predictors, mechanisms associated with the development of severe obesity, novel treatments informed by biologically and psychosocially plausible mechanisms, biopsychosocial phenotypes predicting treatment response, standardization of outcome measures and results reporting in research, and improving clinical care. Substantial gaps in knowledge were identified regarding the basic behavioral, psychosocial, and biological mechanisms driving the development of severe obesity and the influence of these factors on treatment response. Additional exploratory and observational studies are needed to better understand the heterogeneous etiology of severe obesity and explain the high degree of variability observed with interventions. Tailored treatment strategies that may be developed by achieving a better understanding of individual differences in genetic endowment, clinical, metabolic, psychological, and behavioral phenotypes, and response to environmental exposures need to be tested. It is anticipated that these recommendations for future research, including strategies to enhance methodological rigor, will advance precision medicine approaches to treat severe obesity in adolescents more effectively.
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The concepts and ideas presented in this article were conceived by the organizers and participants in a 2017 NIH-sponsored workshop entitled “Developing Precision Medicine Approaches to the Treatment of Severe Obesity in Adolescents.” The authors are grateful for the commitment and dedication from the organizing committee members and speakers for participating in pre-workshop conversations to develop the individual sessions and overall themes. They would also like to express their gratitude to the workshop speakers, discussants, facilitators, and attendees for providing insightful and interactive discussions and recommendations regarding the treatment of severe obesity in adolescents throughout the workshop. Funding for the workshop described in this article was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Heart, Lung and Blood Institute, Office of Behavioral and Social Sciences Research and Office of Disease Prevention. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the U.S. Public Health Service.
Aaron S. Kelly, Ph.D., Center for Pediatric Obesity Medicine, University of Minnesota Medical School; Marsha D. Marcus, Ph.D., University of Pittsburgh School of Medicine; and Jack A. Yanovski, M.D., Ph.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development.
NIH organizing committee members
National Institutes of Diabetes and Digestive and Kidney Diseases: Andrew Bremer, M.D., Mary Evans, Ph.D., Robert Kuczmarski, Dr.PH, Barbara Linder, M.D., Ph.D., Stavroula K. Osganian, M.D., Sc.D., M.P.H. (chair), Pamela Thornton, Ph.D., and Susan Yanovski, M.D.; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health: Layla Esposito, Ph.D., M.A.; National Heart, Lung, and Blood Institute: Charlotte Pratt, Ph.D., R.D.; Office of Behavioral and Social Sciences Research: Christine Hunter, Ph.D., ABPP and Deborah Young-Hyman, Ph.D.; and Office of Disease Prevention: Rachel Ballard, M.D., M.P.H.
Kerri Boutelle, Ph.D., University of California, San Diego School of Medicine; Molly Bray, Ph.D., R.D., L.D., The University of Texas at Austin; Charles Burant, M.D., Ph.D., University of Michigan; Stephen Cook, M.D., M.P.H., University of Rochester Medical Center; Eli Sadaf Farooqi, MBChB, Ph.D., University of Cambridge; Ania Jastreboff, M.D., Ph.D., Yale University School of Medicine; Elissa Jelalian, Ph.D., Alpert Medical School of Brown University; Lee Kaplan, M.D., Ph.D., Harvard Medical School, Massachusetts General Hospital; Aaron S. Kelly, Ph.D., University of Minnesota Medical School; Shelley Kirk, Ph.D., R.D., L.D., Cincinnati Children’s Hospital Medical Center; Thomas Inge, M.D., Ph.D., Children’s Hospital Colorado; Marsha D. Marcus, Ph.D., University of Pittsburgh School of Medicine; Cynthia Ogden, Ph.D., Centers for Disease Control and Prevention; and Meg Zeller, Ph.D., Cincinnati Children’s Hospital Medical Center.
Conflict of interest
Dr. Kelly receives research support (drug/placebo) from Astra Zeneca Pharmaceuticals and serves as a consultant for Novo Nordisk, Orexigen, and Vivus Pharmaceuticals but does not accept personal or professional income for these activities. Dr. Marcus serves on the Scientific Advisory Board of Weight Watchers International, Inc. Dr. J.A. Yanovski receives current research support from Rhythm Pharmaceuticals, Inc. and past research support from Zafgen Inc. for clinical treatment trials of patients with obesity and does not accept personal or professional income for these activities. The remaining authors declare that they have no conflict of interest.
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