Advances in the Science, Treatment, and Prevention of the Disease of Obesity: Reflections From a Diabetes Care Editors' Expert Forum

William T Cefalu, George A Bray, Philip D Home, W Timothy Garvey, Samuel Klein, F Xavier Pi-Sunyer, Frank B Hu, Itamar Raz, Luc Van Gaal, Bruce M Wolfe, Donna H Ryan, William T Cefalu, George A Bray, Philip D Home, W Timothy Garvey, Samuel Klein, F Xavier Pi-Sunyer, Frank B Hu, Itamar Raz, Luc Van Gaal, Bruce M Wolfe, Donna H Ryan

Abstract

As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors' Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease.

Figures

Figure 1
Figure 1
Food available for consumption, 1900–2000. Reprinted from ref. .
Figure 2
Figure 2
Putative factors involved in the pathogenesis and pathophysiology of metabolic dysfunction associated with obesity. CHO, carbohydrate; ChREBP, carbohydrate response element–binding protein; FAS, fatty acid synthase; FFA, free fatty acid; Glut 4, glucose transporter 4; PPARγ, peroxisome proliferator–activated receptor γ; TG, triglyceride.
Figure 3
Figure 3
Percentage of weight change by subject (n = 245) at week 52 of the NYORC weight-loss program. Courtesy of Richard Weil, MEd, CDE (Columbia University, New York, NY); Betty Kovacs, MS, RD (Columbia University, New York, NY); and F.X.P.-S.
Figure 4
Figure 4
Comparative efficacy of weight-loss medications. All data are placebo-subtracted, maximal dose, 1-year results in intention-to-treat populations using last-observation-carried-forward method unless otherwise indicated (–,–162).
Figure 5
Figure 5
Bariatric surgical options. Image courtesy of Walter Pories, MD (East Carolina University, Greenville, NC).
Figure 6
Figure 6
Spectrum of obesity guidelines.

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