Role of Environmental Chemicals in Diabetes and Obesity
Role of Environmental Chemicals in Diabetes and Obesity
Overall, the workshop review of the existing litera-ture supports the plausibility of the "obeso-gen" hypothesis, as well as linkages between type 2 diabetes and exposures to certain chemical classes. A review of the literature indicates very little research has been directed toward understanding associations between environmental exposures and type 1 diabetes. This was considered a critical data gap. Many research questions remain, and an important goal of this workshop was to identify data gaps to stimulate focused research to move the field forward. The research recommendations included suggestions for the most appropriate end points to evaluate in human, animal, and mechanistic studies of diabetes and obesity (Table 2, Table 3, Table 4). All of the breakout groups highlighted the importance of using clinically accepted measures of diabetes and overweight/obesity in the epidemiological studies (Table 4). Understanding more about the different phenotypes of obesity will require more sophisticated measurement methods because the distribution of adipose tissue can vary among individuals with the same BMI and waist circumference. Another series of recommendations was to elucidate the role(s) of effect modifiers, confounding factors, and specific genetic contributions in humans and animal models used to study these diseases (Table 3).
Many of the research gaps were not unique to the field of diabetes/obesity research. The workshop noted a) deficiencies in data on human exposures to many of the chemicals examined, b) the need for better biomarkers of exposure that may be related mechanistically to the disease end points, c) the need for a better understanding of the basic biology of adipocytes, β cells, and neural circuits that regulate feeding behavior in healthy and disease states, and d) the need for an appreciation of how the biology that controls body weight and metabolic set points changes with life stage. A number of the breakout groups noted the need to consider non-monotonic dose–-response relationships for environmental influences on obesity and diabetes. Also, there is a need to consider coexposures between environmental chemicals and consumption of high-calorie, high-carbohydrate, and/or high-fat diets. Finally, workshop participants found the incorporation of HTS information from the Tox21 program to be an intriguing and useful way of improving our understanding of the similarities and differences in biological actions across classes of chemicals and recommended many specific targets for further assay development to further enhance its utility.
NIEHS has already taken steps to address some of the research needs, recognizing that the work will best be accomplished through the combined efforts of the NTP, the NIEHS Division of Extramural Research and Training (DERT), and the NIEHS Division of Intramural Research. Based on the results of this workshop and the data gaps noted, the DERT released program announcements focused on improving our understanding of the role of environmental exposures in the develop-ment of obesity and diabetes (see NIEHS 2011a, 2011b). The announcements have one receipt date per year for the next 3 years. The NTP is organizing further in vitro targeted testing of some of the predictions of chemical effects from the Tox21 screening program and is specifically developing an analytical method to measure organotins in human blood because the lack of exposure data to these compounds was considered a critical research need.
We hope this workshop will stimulate further research to better understand the public health impacts of environmental influences on the increasing international prevalence of diabetes, obesity, and metabolic syndrome. We acknowledge the dedicated efforts of the workshop participants toward achieving this goal.
Conclusions, Research Recommendations, and Next Steps
Overall, the workshop review of the existing litera-ture supports the plausibility of the "obeso-gen" hypothesis, as well as linkages between type 2 diabetes and exposures to certain chemical classes. A review of the literature indicates very little research has been directed toward understanding associations between environmental exposures and type 1 diabetes. This was considered a critical data gap. Many research questions remain, and an important goal of this workshop was to identify data gaps to stimulate focused research to move the field forward. The research recommendations included suggestions for the most appropriate end points to evaluate in human, animal, and mechanistic studies of diabetes and obesity (Table 2, Table 3, Table 4). All of the breakout groups highlighted the importance of using clinically accepted measures of diabetes and overweight/obesity in the epidemiological studies (Table 4). Understanding more about the different phenotypes of obesity will require more sophisticated measurement methods because the distribution of adipose tissue can vary among individuals with the same BMI and waist circumference. Another series of recommendations was to elucidate the role(s) of effect modifiers, confounding factors, and specific genetic contributions in humans and animal models used to study these diseases (Table 3).
Many of the research gaps were not unique to the field of diabetes/obesity research. The workshop noted a) deficiencies in data on human exposures to many of the chemicals examined, b) the need for better biomarkers of exposure that may be related mechanistically to the disease end points, c) the need for a better understanding of the basic biology of adipocytes, β cells, and neural circuits that regulate feeding behavior in healthy and disease states, and d) the need for an appreciation of how the biology that controls body weight and metabolic set points changes with life stage. A number of the breakout groups noted the need to consider non-monotonic dose–-response relationships for environmental influences on obesity and diabetes. Also, there is a need to consider coexposures between environmental chemicals and consumption of high-calorie, high-carbohydrate, and/or high-fat diets. Finally, workshop participants found the incorporation of HTS information from the Tox21 program to be an intriguing and useful way of improving our understanding of the similarities and differences in biological actions across classes of chemicals and recommended many specific targets for further assay development to further enhance its utility.
NIEHS has already taken steps to address some of the research needs, recognizing that the work will best be accomplished through the combined efforts of the NTP, the NIEHS Division of Extramural Research and Training (DERT), and the NIEHS Division of Intramural Research. Based on the results of this workshop and the data gaps noted, the DERT released program announcements focused on improving our understanding of the role of environmental exposures in the develop-ment of obesity and diabetes (see NIEHS 2011a, 2011b). The announcements have one receipt date per year for the next 3 years. The NTP is organizing further in vitro targeted testing of some of the predictions of chemical effects from the Tox21 screening program and is specifically developing an analytical method to measure organotins in human blood because the lack of exposure data to these compounds was considered a critical research need.
We hope this workshop will stimulate further research to better understand the public health impacts of environmental influences on the increasing international prevalence of diabetes, obesity, and metabolic syndrome. We acknowledge the dedicated efforts of the workshop participants toward achieving this goal.
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