Our Response to the Obesity Crisis Reflects Our Bias as a Society

Abstract

This month's issue of Clinical Therapeutics highlights the topic of obesity as a public health issue to which we, as a medical community and society, need to dramatically change our approach. We have curated a collection of commentaries and conversations with several experts in the field of obesity treatment, prevention, and advocacy. The guest contributors make a compelling argument for the classification of obesity as a disease. I offer reasons as to why obesity constitutes a public health emergency and how the current response is woefully insufficient compared to the magnitude of the problem.The burden of obesity in the United States is staggering. In 2018, the prevalence of obesity (defined as a body mass index [BMI] of >30 kg/m2) in the US adult population (aged >18 years) was 42.4%, with almost 10% of cases classified as severe (BMI >40 kg/m2).1Centers for Disease Control and Prevention (CDC). Adult Obesity Facts [CDC website]. Updated February 11, 2021. Available at: https://www.cdc.gov/obesity/data/adult. June 1, 2021.Google Scholar With a US adult population of ~270 million in 2020, these statistics translate to >100 million with obesity and 25 million with severe obesity.2US Census Bureau. Quick Facts—United States 2021 [US Census Bureau website]. Available at: https://www.census.gov/quickfacts/fact/table. June 1, 2021.Google Scholar This prevalence contrasts with those of some other common diseases about which our public health response and attitudes are vastly different: cancer, 1.7 million new cases in 2017; myocardial infarction, 805,000; and coronary artery disease, 6.7% of the adult population.3Centers for Disease Control and Prevention (CDC). Heart Disease Facts [CDC website]. Updated September 8, 2020. Available at: https://www.cdc.gov/heartdisease/facts. June 1, 2021.Google Scholar,4Centers for Disease Control and Prevention (CDC). United States Cancer Statistics: Data Visualizations [CDC website]. 2021. Available at: https://gis.cdc.gov/Cancer/USCS/DataViz. June 1, 2021.Google Scholar In 2019, the National Institutes of Health (NIH) spent $6 billion in annual funding to support research on the treatment and prevention of cancer and $1.4 billion on cardiovascular disease; obesity funding was only $1.1 billion.5National Institutes of Health (NIH)Estimates of Funding for Various Research, Condition, and Disease Categories.February 24, 2020Google Scholar There is a dedicated institute at the NIH for cancer, and cardiovascular disease is a major pillar of another. There is no institute for obesity research; there is not even an office for obesity within the NIH. There is an NIH Obesity Research Task Force, which issued a report in 2011, affirmed in 2019, outlining challenges and opportunities in guiding obesity research.6National Institutes of Health, Obesity Research Task Force. NIH-Supported Obesity Research [NIH website]. 2021. Available at: https://www.obesityresearch.nih.gov. June 1, 2021.Google Scholar Given the complexity of obesity as a disease and the prevalence across the population when compared to other conditions, this response seems grievously inadequate.A core feature of the obesity disease process is chronic inflammation. Among other chemokines, adipocytes secrete interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α, which promote chronic inflammation and metabolic dysfunction.7Maratos-Flier E. Obesity.in: Melmed S. Auchus R.J. Goldfine A.B. Koenig R.J. Rosen C.J. Williams Textbook of Endocrinology. 1. Elsevier, Philadelphia, Pa2020: 1567-1580Google Scholar With the expansion of adipose tissue, immune cells infiltrate the fat and further mediate the inflammatory process.7Maratos-Flier E. Obesity.in: Melmed S. Auchus R.J. Goldfine A.B. Koenig R.J. Rosen C.J. Williams Textbook of Endocrinology. 1. Elsevier, Philadelphia, Pa2020: 1567-1580Google Scholar Why some patients experience poor outcomes of obesity while others seem to be protected is poorly understood. With the onset of the 2009 influenza H1N1 pandemic, obesity gained national attention as a major co-factor of severe disease and mortality.8Webb S.A. Pettila V. Seppelt I. Bellomo R. Bailey M. et al.ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand.N Engl J Med. 2009; 361: 1925-1934Crossref PubMed Scopus (854) Google Scholar,9Morgan O.W. Bramley A. Fowlkes A. Freedman D.S. Taylor T.H. Gargiullo P. et al.Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease.PLoS One. 2010; 5: e9694Crossref PubMed Scopus (323) Google Scholar These observations spawned further study of the dysregulated response to not only influenza infection but also influenza vaccine in patients with obesity.10Paich H.A. Sheridan P.A. Handy J. Karlsson E.A. Schultz-Cherry S. Hudgens M.G. et al.Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus.Obesity (Silver Spring). 2013; 21: 2377-2386Crossref PubMed Scopus (114) Google Scholar, 11Honce R. Karlsson E.A. Wohlgemuth N. Estrada L.D. Meliopoulos V.A. Yao J. et al.Obesity-related microenvironment promotes emergence of virulent influenza virus strains.mBio. 2020; 11 (-19): e03341Crossref PubMed Scopus (68) Google Scholar, 12Sheridan P.A. Paich H.A. Handy J. Karlsson E.A. Hudgens M.G. Sammon A.B. et al.Obesity is associated with impaired immune response to influenza vaccination in humans.Int J Obes (Lond). 2012; 36: 1072-1077Crossref PubMed Scopus (374) Google Scholar These phenomena were replicated with the onset of the coronavirus disease 2019 (COVID-19) pandemic, with similarly high rates of hospitalization and death in patients with obesity.13Goyal P. Choi J.J. Pinheiro L.C. Schenck E.J. Chen R. Jabri A. et al.Clinical characteristics of Covid-19 in New York City.N Engl J Med. 2020; 382: 2372-2374Crossref PubMed Scopus (1315) Google Scholar, 14Goyal P. Ringel J.B. Rajan M. Choi J.J. Pinheiro L.C. Li H.A. et al.Obesity and COVID-19 in New York City: a retrospective cohort study.Ann Intern Med. 2020; 173: 855-858Crossref PubMed Scopus (53) Google Scholar, 15Lighter J. Phillips M. Hochman S. Sterling S. Johnson D. Francois F. et al.Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission.Clin Infect Dis. 2020; 71: 896-897Crossref PubMed Scopus (707) Google Scholar, 16Otto W.R. Geoghegan S. Posch L.C. Bell L.M. Coffin S.E. Sammons J.S. et al.The epidemiology of severe acute respiratory syndrome coronavirus 2 in a pediatric healthcare network in the United States.J Pediatric Infect Dis Soc. 2020; 9: 523-529Crossref PubMed Scopus (0) Google Scholar, 17Foster C.E. Marquez L. Davis A.L. Tocco E. Koy T.H. Dunn J. et al.A surge in pediatric coronavirus disease 2019 cases: the experience of Texas Children's Hospital from March to June 2020.J Pediatric Infect Dis Soc. 2021; 10: 593-598Crossref PubMed Scopus (6) Google Scholar In my practice, virtually all of the children with severe COVID-19 symptoms and hospital admission were adolescents with severe obesity. Similar to the blunted response to influenza vaccine, the findings from an early study suggested that patients with central adiposity who received a COVID-19 mRNA vaccine had a neutralizing antibody level lower than that in patients without central adiposity.18Watanabe M. Balena A. Tuccinardi D. Tozzi R. Risi R. Masi D. et al.Central obesity, smoking habit, and hypertension are associated with lower antibody titres in response to COVID-19 mRNA vaccine.Diabetes Metab Res Rev. 2021 May 6; ([Epub ahead of print])Crossref PubMed Scopus (85) Google Scholar The findings from that immunogenicity study need to be duplicated in larger-scale, population-wide studies, but they raise a concern that patients with obesity may need additional measures for COVID-19 prevention.The experts who contributed to this issue make the point that more options for the treatment of obesity are available than ever before. Six medications have been approved by the US Food and Drug Administration, and a variety of surgical options facilitate weight loss. However, the medications are viewed by insurance payors as "lifestyle medications," similar to agents used for treating nicotine addiction or hair loss, and as a result their costs are not covered by most health insurance plans.19Cohen J. Newly Approved Obesity Drug Wegovy Holds Promise, But Faces Reimbursement Challenges.June 5, 2021https://www.forbes.com/sites/joshuacohen/2021/06/05/obesity-drug-wegovy-holds-promise-but-faces-reimbursement-challenges/?sh=558ecdc04bd5Google Scholar A study authored by Dr. Fatima Stanford, one of the experts contributing to this issue, demonstrated that most public insurance plans in the United States offer no coverage at all for the costs of anti-obesity medications.20Gomez G. Stanford F.C. US health policy and prescription drug coverage of FDA-approved medications for the treatment of obesity.Int J Obes (Lond). 2018; 42: 495-500Crossref PubMed Scopus (38) Google Scholar The ones that cover medication costs do so only for patients who pay the highest premiums, or they cover the costs of the medications that appear to be least effective. This lack of coverage extends to diet counseling for patients and their families, which costs a fraction of the costs of medical and surgical treatment options. In a modeling study in Medicare recipients, a combination of cognitive–behavioral therapy and medication was cost-saving over a 10-year period.21Chen F. Su W. Ramasamy A. Zvenyach T. Kahan S. Kyle T. et al.Ten-year Medicare budget impact of increased coverage for anti-obesity intervention.J Med Econ. 2019; 22: 1096-1104Crossref PubMed Scopus (5) Google Scholar As the US health care system slowly transitions to a value-based payment model, it is hoped that these coverage trends will improve.Given the prevalences of obesity and severe obesity, clinicians need to carefully consider how to dose medications in patients with obesity. The presence of obesity in any adult or child can dramatically change drug metabolism, and the dose recommended for nonobese adults may be insufficient for treating diseases in patients with obesity.22Brill M.J. Diepstraten J. van Rongen A. van Kralingen S. van den Anker J.N. Knibbe C.A. Impact of obesity on drug metabolism and elimination in adults and children.Clin Pharmacokinet. 2012; 51: 277-304Crossref PubMed Scopus (239) Google Scholar While the earlier-mentioned mortality rate in patients with severe infection may be entirely attributable to obesity-related immune dysregulation, it is worth considering that suboptimal dosing of medications needed for supportive care may also play a role. We at Clinical Therapeutics are proud to be a forum for publishing research on this topic. A search of the term obesity on our website yielded 770 articles, and we have organized several prior Topic Updates on various aspects of obesity that are freely available to all (https://www.clinicaltherapeutics.com/content/specialfocus). We continue to welcome studies that advance our understanding of how to best treat patients with obesity.We sincerely thank the experts who contributed to this Update. Their continued advocacy of their patients should be an example for all of us. We hope that the articles encourage you as clinicians and researchers to reflect on ways to help advance the care of patients with obesity. The first steps may be to look in the mirror and determine whether you harbor the most common biases and assumptions about patients with obesity, and then to make changes to counter those biases. This month's issue of Clinical Therapeutics highlights the topic of obesity as a public health issue to which we, as a medical community and society, need to dramatically change our approach. We have curated a collection of commentaries and conversations with several experts in the field of obesity treatment, prevention, and advocacy. The guest contributors make a compelling argument for the classification of obesity as a disease. I offer reasons as to why obesity constitutes a public health emergency and how the current response is woefully insufficient compared to the magnitude of the problem. The burden of obesity in the United States is staggering. In 2018, the prevalence of obesity (defined as a body mass index [BMI] of >30 kg/m2) in the US adult population (aged >18 years) was 42.4%, with almost 10% of cases classified as severe (BMI >40 kg/m2).1Centers for Disease Control and Prevention (CDC). Adult Obesity Facts [CDC website]. Updated February 11, 2021. Available at: https://www.cdc.gov/obesity/data/adult. June 1, 2021.Google Scholar With a US adult population of ~270 million in 2020, these statistics translate to >100 million with obesity and 25 million with severe obesity.2US Census Bureau. Quick Facts—United States 2021 [US Census Bureau website]. Available at: https://www.census.gov/quickfacts/fact/table. June 1, 2021.Google Scholar This prevalence contrasts with those of some other common diseases about which our public health response and attitudes are vastly different: cancer, 1.7 million new cases in 2017; myocardial infarction, 805,000; and coronary artery disease, 6.7% of the adult population.3Centers for Disease Control and Prevention (CDC). Heart Disease Facts [CDC website]. Updated September 8, 2020. Available at: https://www.cdc.gov/heartdisease/facts. June 1, 2021.Google Scholar,4Centers for Disease Control and Prevention (CDC). United States Cancer Statistics: Data Visualizations [CDC website]. 2021. Available at: https://gis.cdc.gov/Cancer/USCS/DataViz. June 1, 2021.Google Scholar In 2019, the National Institutes of Health (NIH) spent $6 billion in annual funding to support research on the treatment and prevention of cancer and $1.4 billion on cardiovascular disease; obesity funding was only $1.1 billion.5National Institutes of Health (NIH)Estimates of Funding for Various Research, Condition, and Disease Categories.February 24, 2020Google Scholar There is a dedicated institute at the NIH for cancer, and cardiovascular disease is a major pillar of another. There is no institute for obesity research; there is not even an office for obesity within the NIH. There is an NIH Obesity Research Task Force, which issued a report in 2011, affirmed in 2019, outlining challenges and opportunities in guiding obesity research.6National Institutes of Health, Obesity Research Task Force. NIH-Supported Obesity Research [NIH website]. 2021. Available at: https://www.obesityresearch.nih.gov. June 1, 2021.Google Scholar Given the complexity of obesity as a disease and the prevalence across the population when compared to other conditions, this response seems grievously inadequate. A core feature of the obesity disease process is chronic inflammation. Among other chemokines, adipocytes secrete interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α, which promote chronic inflammation and metabolic dysfunction.7Maratos-Flier E. Obesity.in: Melmed S. Auchus R.J. Goldfine A.B. Koenig R.J. Rosen C.J. Williams Textbook of Endocrinology. 1. Elsevier, Philadelphia, Pa2020: 1567-1580Google Scholar With the expansion of adipose tissue, immune cells infiltrate the fat and further mediate the inflammatory process.7Maratos-Flier E. Obesity.in: Melmed S. Auchus R.J. Goldfine A.B. Koenig R.J. Rosen C.J. Williams Textbook of Endocrinology. 1. Elsevier, Philadelphia, Pa2020: 1567-1580Google Scholar Why some patients experience poor outcomes of obesity while others seem to be protected is poorly understood. With the onset of the 2009 influenza H1N1 pandemic, obesity gained national attention as a major co-factor of severe disease and mortality.8Webb S.A. Pettila V. Seppelt I. Bellomo R. Bailey M. et al.ANZIC Influenza Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand.N Engl J Med. 2009; 361: 1925-1934Crossref PubMed Scopus (854) Google Scholar,9Morgan O.W. Bramley A. Fowlkes A. Freedman D.S. Taylor T.H. Gargiullo P. et al.Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza A(H1N1) disease.PLoS One. 2010; 5: e9694Crossref PubMed Scopus (323) Google Scholar These observations spawned further study of the dysregulated response to not only influenza infection but also influenza vaccine in patients with obesity.10Paich H.A. Sheridan P.A. Handy J. Karlsson E.A. Schultz-Cherry S. Hudgens M.G. et al.Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus.Obesity (Silver Spring). 2013; 21: 2377-2386Crossref PubMed Scopus (114) Google Scholar, 11Honce R. Karlsson E.A. Wohlgemuth N. Estrada L.D. Meliopoulos V.A. Yao J. et al.Obesity-related microenvironment promotes emergence of virulent influenza virus strains.mBio. 2020; 11 (-19): e03341Crossref PubMed Scopus (68) Google Scholar, 12Sheridan P.A. Paich H.A. Handy J. Karlsson E.A. Hudgens M.G. Sammon A.B. et al.Obesity is associated with impaired immune response to influenza vaccination in humans.Int J Obes (Lond). 2012; 36: 1072-1077Crossref PubMed Scopus (374) Google Scholar These phenomena were replicated with the onset of the coronavirus disease 2019 (COVID-19) pandemic, with similarly high rates of hospitalization and death in patients with obesity.13Goyal P. Choi J.J. Pinheiro L.C. Schenck E.J. Chen R. Jabri A. et al.Clinical characteristics of Covid-19 in New York City.N Engl J Med. 2020; 382: 2372-2374Crossref PubMed Scopus (1315) Google Scholar, 14Goyal P. Ringel J.B. Rajan M. Choi J.J. Pinheiro L.C. Li H.A. et al.Obesity and COVID-19 in New York City: a retrospective cohort study.Ann Intern Med. 2020; 173: 855-858Crossref PubMed Scopus (53) Google Scholar, 15Lighter J. Phillips M. Hochman S. Sterling S. Johnson D. Francois F. et al.Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission.Clin Infect Dis. 2020; 71: 896-897Crossref PubMed Scopus (707) Google Scholar, 16Otto W.R. Geoghegan S. Posch L.C. Bell L.M. Coffin S.E. Sammons J.S. et al.The epidemiology of severe acute respiratory syndrome coronavirus 2 in a pediatric healthcare network in the United States.J Pediatric Infect Dis Soc. 2020; 9: 523-529Crossref PubMed Scopus (0) Google Scholar, 17Foster C.E. Marquez L. Davis A.L. Tocco E. Koy T.H. Dunn J. et al.A surge in pediatric coronavirus disease 2019 cases: the experience of Texas Children's Hospital from March to June 2020.J Pediatric Infect Dis Soc. 2021; 10: 593-598Crossref PubMed Scopus (6) Google Scholar In my practice, virtually all of the children with severe COVID-19 symptoms and hospital admission were adolescents with severe obesity. Similar to the blunted response to influenza vaccine, the findings from an early study suggested that patients with central adiposity who received a COVID-19 mRNA vaccine had a neutralizing antibody level lower than that in patients without central adiposity.18Watanabe M. Balena A. Tuccinardi D. Tozzi R. Risi R. Masi D. et al.Central obesity, smoking habit, and hypertension are associated with lower antibody titres in response to COVID-19 mRNA vaccine.Diabetes Metab Res Rev. 2021 May 6; ([Epub ahead of print])Crossref PubMed Scopus (85) Google Scholar The findings from that immunogenicity study need to be duplicated in larger-scale, population-wide studies, but they raise a concern that patients with obesity may need additional measures for COVID-19 prevention. The experts who contributed to this issue make the point that more options for the treatment of obesity are available than ever before. Six medications have been approved by the US Food and Drug Administration, and a variety of surgical options facilitate weight loss. However, the medications are viewed by insurance payors as "lifestyle medications," similar to agents used for treating nicotine addiction or hair loss, and as a result their costs are not covered by most health insurance plans.19Cohen J. Newly Approved Obesity Drug Wegovy Holds Promise, But Faces Reimbursement Challenges.June 5, 2021https://www.forbes.com/sites/joshuacohen/2021/06/05/obesity-drug-wegovy-holds-promise-but-faces-reimbursement-challenges/?sh=558ecdc04bd5Google Scholar A study authored by Dr. Fatima Stanford, one of the experts contributing to this issue, demonstrated that most public insurance plans in the United States offer no coverage at all for the costs of anti-obesity medications.20Gomez G. Stanford F.C. US health policy and prescription drug coverage of FDA-approved medications for the treatment of obesity.Int J Obes (Lond). 2018; 42: 495-500Crossref PubMed Scopus (38) Google Scholar The ones that cover medication costs do so only for patients who pay the highest premiums, or they cover the costs of the medications that appear to be least effective. This lack of coverage extends to diet counseling for patients and their families, which costs a fraction of the costs of medical and surgical treatment options. In a modeling study in Medicare recipients, a combination of cognitive–behavioral therapy and medication was cost-saving over a 10-year period.21Chen F. Su W. Ramasamy A. Zvenyach T. Kahan S. Kyle T. et al.Ten-year Medicare budget impact of increased coverage for anti-obesity intervention.J Med Econ. 2019; 22: 1096-1104Crossref PubMed Scopus (5) Google Scholar As the US health care system slowly transitions to a value-based payment model, it is hoped that these coverage trends will improve. Given the prevalences of obesity and severe obesity, clinicians need to carefully consider how to dose medications in patients with obesity. The presence of obesity in any adult or child can dramatically change drug metabolism, and the dose recommended for nonobese adults may be insufficient for treating diseases in patients with obesity.22Brill M.J. Diepstraten J. van Rongen A. van Kralingen S. van den Anker J.N. Knibbe C.A. Impact of obesity on drug metabolism and elimination in adults and children.Clin Pharmacokinet. 2012; 51: 277-304Crossref PubMed Scopus (239) Google Scholar While the earlier-mentioned mortality rate in patients with severe infection may be entirely attributable to obesity-related immune dysregulation, it is worth considering that suboptimal dosing of medications needed for supportive care may also play a role. We at Clinical Therapeutics are proud to be a forum for publishing research on this topic. A search of the term obesity on our website yielded 770 articles, and we have organized several prior Topic Updates on various aspects of obesity that are freely available to all (https://www.clinicaltherapeutics.com/content/specialfocus). We continue to welcome studies that advance our understanding of how to best treat patients with obesity. We sincerely thank the experts who contributed to this Update. Their continued advocacy of their patients should be an example for all of us. We hope that the articles encourage you as clinicians and researchers to reflect on ways to help advance the care of patients with obesity. The first steps may be to look in the mirror and determine whether you harbor the most common biases and assumptions about patients with obesity, and then to make changes to counter those biases. I thank Dr. Caren Mangarelli for her input on the style and content of this editorial. Appendix. 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