Is Supersize More than Just Too Much Food?

Diabetes and obesity are two of the most significant public health issues of our day, and both are major epidemics in the United States and abroad. These conditions are interrelated; obesity has been long recognized as a common precursor to adult-onset (type 2) diabetes, although “adult-onset” is becoming an outdated term. In the United States, the prevalence of obesity among children and adolescents has almost tripled since 1980, and an estimated 12.5 million children and adolescents (16.9%) are considered obese (Ogden and Carroll 2010). This trend is also apparent in preschool children 2–5 years of age, a group in which obesity increased from 5% in 1976–1980 to 10.4% in 2007–2008 (Ogden and Carroll 2010). One report based on well-child visits at a health maintenance organization in Massachusetts was particularly disturbing: The prevalence of overweight in infants 0–6 months of age almost doubled between 1980 and 2001, from 3.4% to 5.9% (Kim et al. 2006). This finding suggests that factors other than changes in physical activity or diet are contributing to these trends, pointing to possible changes in fetal programming. 
 
The most recent estimates of diabetes prevalence in the United States are equally staggering. Based on data from 2005 through 2008, 25.6 million (11.3%) of all people in the United States ≥ 20 years of age have diagnosed or undiagnosed diabetes (Centers for Disease Control and Prevention 2011). Another 35% have prediabetes, a condition in which blood glucose is higher than normal but not high enough to be classified as diabetes. People with prediabetes have an increased risk of developing type 2 diabetes, heart disease, and stroke. 
 
Being overweight or obese has been estimated to account for approximately 70% of the cases of type 2 diabetes (Eyre et al. 2004). However, the etiology of the remaining 30% is unknown. Given the sheer numbers of people with the disease—now estimated globally at 220 million and expected to grow to 366 million by 2030 (World Health Organization 2011)—it is easy to understand the growing consideration of “nontraditional” risk factors (e.g., environmental chemicals, stress, microbiome) as contributors to these diseases. A growing scientific literature implicating a role for environmental chemical exposures has been developed largely through the funding of the National Institute of Environmental Health Sciences (NIEHS) as part of the institute’s broader interest in understanding endocrine-related disorders and the developmental origins of adult disease. Endocrine-disrupting chemicals alter control of adipose tissue development and function, control of food intake, insulin sensitivity, glucose homeostasis, and lipid metabolism (Janesick and Blumberg 2011; Nadal et al. 2009; Thayer et al. 2012). If the exposure occurs during development, the result could possibly be an altered “set point” or sensitivity for developing obesity or diabetes later in life. 
 
Research addressing the role of environmental chemicals in diabetes and obesity has rapidly expanded in the past several years. Both the May 2010 White House Task Force on Childhood Obesity (2010) and the 31 March 2011 Strategic Plan for NIH Obesity Research [NIH (National Institutes of Health) Obesity Research Task Force 2011] acknowledge the growing science base in this area and cite the need to understand more about the role of environmental exposures as part of future research and prevention strategies. 
 
To help develop such a research strategy, the National Toxicology Program (NTP), with collaboration from the NIEHS intramural and extramural program scientists, organized a state-of-the-science workshop in January 2011 titled “Role of Environmental Chemicals in the Development of Diabetes and Obesity.” The technical background documents assembled for this workshop were extensive, totaling > 500 pages and spanning the range from epidemiological data to high throughput screening results. As an additional scientific resource, approximately 800 main findings from the epidemiological studies of diabetes and childhood obesity have been compiled into a searchable graphing software program. A diverse group of > 150 scientists, including toxicologists, epidemiologists, and bioinformaticists, as well as experts in the pathobiology of diabetes and obesity, attended the meeting to review the existing literature and shape a research strategy. 
 
The review of the collected literature supported the plausibility of certain environmental chemicals acting as “obesogens” or diabetogenic agents. In some cases, the conclusions were based on surprisingly consistent epidemiological associations. With other chemicals or chemical classes, consistency was found in mechanisms of action. We have little appreciation for the extent to which environmental chemical exposures may be influencing obesity and diabetes rates, but it is becoming increasingly clear that overnutrition and a lack of exercise are not the entire story. 
 
The first of a series of articles stemming from the January 2011 workshop appears in this issue of Environmental Health Perspectives (Thayer et al. 2012). Kristina Thayer, director of the NTP Office of Health Assessment and Translation, other NIEHS staff, and the workshop chair, Michael Gallo (University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School) provide an introduction to the topic and an orientation to the workshop and key outcomes. Upcoming reports will examine the influence of smoking during pregnancy, as well as nicotine and arsenic exposures, on diabetes and obesity outcomes and mechanisms.

Diabetes and obesity are two of the most significant public health issues of our day, and both are major epidemics in the United States and abroad. These conditions are inter related; obesity has been long recognized as a common precursor to adult-onset (type 2) diabetes, although "adult-onset" is becoming an outdated term. In the United States, the prevalence of obesity among children and adolescents has almost tripled since 1980, and an estimated 12.5 million children and adolescents (16.9%) are considered obese (Ogden and Carroll 2010). This trend is also apparent in preschool children 2-5 years of age, a group in which obesity increased from 5% in 1976-1980to 10.4% in 2007-2008(Ogden and Carroll 2010. One report based on wellchild visits at a health maintenance organization in Massachusetts was particularly disturbing: The prevalence of over weight in infants 0-6 months of age almost doubled between 1980 and 2001, from 3.4% to 5.9% (Kim et al. 2006). This finding suggests that factors other than changes in physical activity or diet are contributing to these trends, pointing to possible changes in fetal programming.
The most recent estimates of diabetes prevalence in the United States are equally staggering. Based on data from 2005 through 2008, 25.6 million (11.3%) of all people in the United States ≥ 20 years of age have diagnosed or undiagnosed diabetes (Centers for Disease Control and Prevention 2011). Another 35% have pre diabetes, a condition in which blood glucose is higher than normal but not high enough to be classified as diabetes. People with pre diabetes have an increased risk of developing type 2 diabetes, heart disease, and stroke.
Being overweight or obese has been estimated to account for approximately 70% of the cases of type 2 diabetes (Eyre et al. 2004). However, the etiology of the remaining 30% is unknown. Given the sheer numbers of people with the disease-now estimated globally at 220 million and expected to grow to 366 million by 2030 (World Health Organization 2011)-it is easy to understand the growing consideration of "non traditional" risk factors (e.g., environ mental chemicals, stress, micro biome) as contributors to these diseases. A growing scientific literature implicating a role for environmental chemical exposures has been developed largely through the funding of the National Institute of Environmental Health Sciences (NIEHS) as part of the institute's broader interest in understanding endocrinerelated disorders and the develop mental origins of adult disease. Endocrine-disrupting chemicals alter control of adipose tissue development and function, control of food intake, insulin sensitivity, glucose homeo stasis, and lipid metabolism (Janesick and Blumberg 2011;Nadal et al. 2009;Thayer et al. 2012). If the exposure occurs during develop ment, the result could possibly be an altered "set point" or sensitivity for developing obesity or diabetes later in life.
Research addressing the role of environmental chemicals in diabetes and obesity has rapidly expanded in the past several years. To help develop such a research strategy, the National Toxicology Program (NTP), with collaboration from the NIEHS intramural and extramural program scientists, organized a state-of-the-science workshop in January 2011 titled "Role of Environmental Chemicals in the Development of Diabetes and Obesity." The technical background documents assembled for this workshop were extensive, totaling > 500 pages and spanning the range from epidemiological data to high throughput screening results. As an additional scientific resource, approximately 800 main findings from the epidemiological studies of diabetes and childhood obesity have been compiled into a searchable graphing software program. A diverse group of > 150 scientists, including toxicologists, epidemiologists, and bioinformaticists, as well as experts in the pathobiology of diabetes and obesity, attended the meeting to review the existing literature and shape a research strategy.
The review of the collected literature supported the plausibility of certain environmental chemicals acting as "obesogens" or diabeto genic agents. In some cases, the conclusions were based on surprisingly consistent epidemiological associations. With other chemicals or chemical classes, consistency was found in mechanisms of action. We have little appreciation for the extent to which environ mental chemi cal exposures may be influencing obesity and diabetes rates, but it is becoming increasingly clear that over nutrition and a lack of exercise are not the entire story.
The first of a series of articles stemming from the January 2011 workshop appears in this issue of Environmental Health Perspectives (Thayer et al. 2012). Kristina Thayer, director of the NTP Office of Health Assessment and Translation, other NIEHS staff, and the workshop chair, Michael Gallo (University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School) provide an introduction to the topic and an orientation to the workshop and key outcomes. Upcoming reports will examine the influence of smoking during pregnancy, as well as nicotine and arsenic exposures, on diabetes and obesity outcomes and mechanisms.
The author declares she has no actual or potential competing financial interests.  brought together a group of 50 scientists and stake holders to work jointly to gather and analyze existing data and to publish synthesis papers on the fate of mercury from its environmental sources to seafood consumersissues of critical importance for informing public policy.

Linda S. Birnbaum
Mercury, particularly its organic form (MeHg), is a global contaminant and toxicant of major concern for humans and wildlife (Driscoll et al. 2007;Fitzgerald et al. 2007;Grandjean et al. 2005;Mahaffey et al. 2009). Mercury is third (after arsenic and lead) on the 2011 Agency for Toxic Substances and Disease Registry (ATSDR) priority list of 275 hazardous substances (ATSDR 2011), which includes substances that present the most significant potential threats to human health in the United States. MeHg has long been known as a potent neuro toxicant, particularly due to incidents of acute and high-level exposures (e.g., Minimata, Japan; Iraq), but neurological effects have been documented in island populations that consume large quantities of marine mammals or seafood (Axelrad et al. 2007;Cohen et al. 2005;Rice 2004). Moreover, recent epidemiologic studies have revealed evidence of a range of health effects in adults and children at MeHg exposure levels lower than previously observed (Lynch et al. 2010;Mergler et al. 2007;Oken et al. 2008). In this issue of EHP, Karagas et al. (2012) provide a comprehensive review of the current scientific evidence for effects of low-level exposures to MeHg on birth outcomes, neuro cognitive outcomes, the cardio vascular system, and immune function. The authors recommend that future studies investigate sex-specific effects and genetic susceptibility, and that they include more precise exposure indicators, outcome measures with mechanistic bases, and consideration of non linear dose-response relation ships. Their review helps to set the stage for future research on the human effects of low-level MeHg exposure. Fish are the most important agents of MeHg exposure for humans, and consumption of contaminated fish is a serious public health concern (Mahaffey et al. 2009;Oken et al. 2005;Sunderland 2007 (2012) discuss the wide range of trade-offs facing fish consumers and the difficulties in evaluating current fish consumption advice. Consumers need to consider not only the contaminant concentrations in fish but also their nutritional value, the sustainability of the fishery, and the cost of different fish choices. Moreover, there is little guidance for specific sub populations with different exposure risks due to factors such as age or baseline intake of fish. The authors recommend that fish consumption advice address these multiple perspectives and provide a clear and simple message. Ultimately, fish consumption advice should protect public health on a global scale and promote sustainability of the world's fisheries as a critical source of human nutrition.
Currently, important national and international policy decisions are being made concerning the environmental impacts of mercury. The widespread threat to human health posed by MeHg has prompted the United States to pass a mercury rule for controlling atmospheric emissions (U.S. EPA 2011) and the UNEP to forge a broad consensus