The past two decades have witnessed a dramatic rise of obesity prevalence and a parallel leap of type 2 diabetes (T2D) prevalence. Although there are clear genetic determinants for both conditions, solid evidence proves that both conditions can also be prevented through lifestyle and dietary intervention on modifiable risk factors. Meanwhile, evidence now suggests that some environmental pollutants, especially the persistent organic pollutants (POPs), may also lead to increased risk of both obesity and T2D. Accumulating data from animal studies have linked a few POPs, such as polychlorinated biphenyls (PCBs) and p,p'- dichlorodiphenyldichloethylene (p,p'-DDE), with weight gain and insulin resistance. Human studies are rare in this field and most of the existing studies used a cross-sectional design, which cannot establish causal relationship or timeline between exposures and outcomes. Moreover, our preliminary data from epidemiologic observation and system biology simulation have suggested that hexachlorobenzene (HCB), a POP primarily deemed to be merely a marker of long-term total POP exposure, may be causally associated with risk of diabetes. In addition, new POPs that have entered the environment, such as the perfluorinated compounds (PFCs), have received little attention with respect to their effects on obesity and T2D. To narrow the gap in science in this regard, we aim to evaluate PCBs, DDE, HCB, and PFCs in relation to 1) subsequent weight gain, 2) development of newly diagnosed type 2 diabetes, and 3) markers of insulin resistance/glucose metabolism abnormalities, including fasting insulin, hemoglobin-A1c, and total adiponectin, in young and middle-aged women who participated in a well-characterized prospective cohort: The Nurses'Health Study (NHS) II. We will also explore lifestyle and dietary determinants of the POPs and potential interactions between POPs and other risk factors on obesity and diabetes in this cohort. The NHS II provides a unique and ideal opportunity for us to examine the aims. Since the study baseline in 1991, extremely rich data on lifestyle, diet, medical history have been repeatedly collected every 2 to 4 years. Moreover, in 1994-1995, blood samples were provided by approximately 30,000 NHS II participants, who comprised the study population for the current investigation. Among these participants, we will conduct a nested case-control study of type 2 diabetes, which is expected to include 1,050 incident type 2 diabetes cases at age 45 or older and the equal number of matched controls. Rigorous quality control protocol and processes have been and will be continuously applied in the NHS II cohort to ensure the highest quality of research data. In addition, we have assembled an outstanding research team comprised of well-established researchers in multi-disciplinary fields including environmental health, nutrition, and biostatistics that will ensure the successful implementation of the project. In summary, the current investigation will provide novel and critical evidence that will not only greatly expand ou knowledge of the diabetogenic effects of POPs, but also inform public health policy-making to help prevent obesity and T2D.

Public Health Relevance

While diabetes is a preventable disease, identification of novel modifiable risk factors is necessary. The proposed investigation aims to utilize data from a large prospective cohort of young women to examine whether exposures to environmental pollutants (such as PCBs, DDE, hexachlorobenzene, and perfluorinated compounds) at early adult life will lead to elevated diabetes risk at later ages. The study will shed new light on the causal relationship between the suspected chemical exposures and diabetes risk, and to help shape new public health policies to facilitate diabetes prevention.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Research Project (R01)
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Kidney, Nutrition, Obesity and Diabetes (KNOD)
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Heindel, Jerrold
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Harvard University
Schools of Public Health
United States
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Zong, Geng; Valvi, Damaskini; Coull, Brent et al. (2018) Persistent organic pollutants and risk of type 2 diabetes: A prospective investigation among middle-aged women in Nurses' Health Study II. Environ Int 114:334-342
Sun, Qi; Zong, Geng; Valvi, Damaskini et al. (2018) Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes: A Prospective Investigation among U.S. Women. Environ Health Perspect 126:037001
Chiu, Yu-Han; Williams, Paige L; Mínguez-Alarcón, Lidia et al. (2018) Comparison of questionnaire-based estimation of pesticide residue intake from fruits and vegetables with urinary concentrations of pesticide biomarkers. J Expo Sci Environ Epidemiol 28:31-39
Zong, Geng; Lebwohl, Benjamin; Hu, Frank B et al. (2018) Gluten intake and risk of type 2 diabetes in three large prospective cohort studies of US men and women. Diabetologia 61:2164-2173
Hu, Yang; Zong, Geng; Liu, Gang et al. (2018) Smoking Cessation, Weight Change, Type 2 Diabetes, and Mortality. N Engl J Med 379:623-632
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Liu, Gang; Zong, Geng; Hu, Frank B et al. (2017) Cooking Methods for Red Meats and Risk of Type 2 Diabetes: A Prospective Study of U.S. Women. Diabetes Care 40:1041-1049
Liu, Gang; Sun, Qi (2017) Response by Liu and Sun to Letter Regarding Article, ""Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes: A 22-Year Prospective Study"". Arterioscler Thromb Vasc Biol 37:e57
Juan, Juan; Liu, Gang; Willett, Walter C et al. (2017) Whole Grain Consumption and Risk of Ischemic Stroke: Results From 2 Prospective Cohort Studies. Stroke 48:3203-3209
Liu, Gang; Zong, Geng; Doty, Richard L et al. (2016) Prevalence and risk factors of taste and smell impairment in a nationwide representative sample of the US population: a cross-sectional study. BMJ Open 6:e013246

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