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INTRODUCTION

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Prevalence rates of obesity rates have increased sharply worldwide over the past 30 years.1 Worldwide, the proportion of adults with a body mass index (BMI) of 25 kg/m2 or greater increased between 1980 and 2013 from 28.8% to 36.9% in men, and from 29.8% to 38.0% in women.2 Prevalence has increased substantially in children and adolescents in developed countries to the point where 23.8% of boys and 22.6% of girls were overweight or obese in 2013.2 In the United States, data from the National Health and Nutrition Examination Survey (NHANES) show that roughly two out of three US adults are overweight or obese, more than one-third are obese, and 17% of children are obese.3,4 This has created a global health crisis with a profound impact on morbidity, mortality, and health care costs largely attributable to weight-related complications.

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In recent years, accumulating scientific evidence has confirmed that obesity is a chronic disease with interacting genetic, environmental, and behavioral determinants resulting in serious complications.5,6 In addition, exciting advances have occurred in all three treatment modalities for obesity: lifestyle intervention; pharmacotherapy; and weight-loss procedures, including bariatric surgery.6,7,8,9,10 Clinical trials have established the efficacy of lifestyle and behavioral interventions in the treatment of obesity, and refinements in surgical approaches and improved preoperative and postoperative care have improved outcomes of bariatric surgery. Importantly, there are now five weight-loss medications approved by the US Food and Drug Administration (FDA) for chronic management.6,7,8,9 These new therapeutic tools together with advances in our scientific understanding of obesity have led to the development of rational medical care models and evidence-based therapeutic approaches with the goal of improving patient health.

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PATHOPHYSIOLOGY OF OBESITY: A CHRONIC DISEASE

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Obesity is a Chronic Disease

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The pathophysiology of obesity produces excess adiposity sufficient to impair health and results from an imbalance between caloric intake and energy expenditure in favor of fat accretion. In 2012, the American Association of Clinical Endocrinologists (AACE) published a position statement designating obesity as a disease.5 Subsequently, following a proposition submitted by AACE together with multiple other professional organizations, the American Medical Association (AMA) also recognized obesity as a chronic disease in June, 2013.11 Like many other chronic diseases, genetic factors constitute a substantial component of disease risk12 that can explain 50% to 60% of individual variation in body weight in monozygotic/dizygotic twin studies. Monogenic forms of the disease are rare, such as in families with leptin or leptin receptor mutations or deletion of the SNORD116 gene cluster in patients with Prader-Willi syndrome. Susceptibility to obesity in the majority of individuals results from the inheritance of multiple genes with each allele conferring a very small relative risk for the disease. Genome-wide association studies have identified more than 100 susceptibility ...

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