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

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          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.

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          Most cited references100

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          2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society.

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            Excess deaths associated with underweight, overweight, and obesity.

            As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. To estimate deaths associated with underweight (body mass index [BMI] or =30) in the United States in 2000. We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. Number of excess deaths in 2000 associated with given BMI levels. Relative to the normal weight category (BMI 18.5 to or =30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight with 33,746 excess deaths (95% CI, 15,726-51,766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.
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              Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial.

              The effectiveness of intentional weight loss in reducing cardiovascular disease (CVD) events in type 2 diabetes is unknown. This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events. This study consisted of a multicentered, randomized, controlled trial of 5,145 individuals with type 2 diabetes, aged 45-74 years, with BMI >25 kg/m2 (>27 kg/m2 if taking insulin). An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition. Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants (all P < 0.01). At 1 year, ILI resulted in clinically significant weight loss in people with type 2 diabetes. This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE. Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                August 2015
                14 July 2015
                : 38
                : 8
                : 1567-1582
                Affiliations
                [1] 1Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
                [2] 2Newcastle University, Newcastle upon Tyne, U.K.
                [3] 3Department of Nutrition Sciences, University of Alabama at Birmingham and Birmingham Veterans Affairs Medical Center, Birmingham, AL
                [4] 4Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO
                [5] 5Obesity Research Center, Department of Medicine, Columbia University, New York, NY
                [6] 6Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
                [7] 7Department of Internal Medicine, Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
                [8] 8Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, Antwerp, Belgium
                [10] 9Department of Surgery, Oregon Health and Science University, Portland, OR
                Author notes
                Corresponding author: William T. Cefalu, william.cefalu@ 123456pbrc.edu .
                Article
                1081
                10.2337/dc15-1081
                4831905
                26421334
                27e06026-ebea-4773-96b6-4a43c30d01f2
                © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
                History
                Page count
                Pages: 16
                Funding
                Funded by: National Institute of General Medical Sciences http://dx.doi.org/10.13039/100000057
                Award ID: 1 U54 GM104940
                Categories
                Diabetes Care Expert Forum

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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