(left to right) David Q. Rich, ScD, assistant professor, Department of Epidemiology, UMDNJ-School of Public Health (SPH); Sampada Gandhi, MD, MPH, research teaching specialist, doctoral student in public health; Howard M. Kipen, MD, MPH, professor of environmental and occupational medicine, UMDNJ-Robert Wood Johnson Medical School and SPH; Jicheng Gong, doctoral student in public health

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iabetes is a leading cause of morbidity and mortality in the developed world, particularly aggravating atherosclerosis and increasing the risk for other acute cardiovascular conditions such as myocardial infarction (MI) and stroke. Of great concern is that Type II diabetes (adult onset) is increasing at alarming rates, particularly in the U.S., which is likely associated with concomitantly increasing rates of overweight and obesity.

Less well-appreciated is that particle air pollution (soot) has been convincingly documented in epidemiology studies to contribute to or cause cardiovascular conditions such as hypertension, MI, arrhythmias, stroke, hypertension, and exacerbations of congestive heart failure. Further, other research has specifically suggested that exposures to air pollution during commuting to and from work may be a trigger of MIs as well. However, validation of specific biological mechanisms to explain how particle air pollution leads to these endpoints is incomplete. Such mechanistic knowledge would strengthen scientific arguments for primary prevention of health effects associated with air pollution. Ideally, mechanistic knowledge may also allow development of methods of secondary prevention (e.g. reduce activities at times when particularly potent types of pollution such as ozone or fine particles are present). Understanding these mechanisms may also suggest the use of specific medications and/or dietary intake of specific nutrients (e.g. omega 3 fatty acids) that can be targeted to interfere with the specific pathophysiologic mechanism(s) of a type of air pollution. This may be particularly effective for those at highest risk by virtue of inheritance or preexisting disease, or for those who live in the most polluted areas, such as Beijing, Mexico City, and other cities in developing countries.

Even less well-appreciated is the epidemiological evidence that diabetics may be more susceptible to the clinical effects of air pollution on the heart. The interaction between diabetes and air pollution means that diabetics may be one of several particularly susceptible groups, along with the elderly, infants, asthmatics, etc., who may benefit most from actions to reduce pollution or ameliorate its impact on the body. The present pilot research, funded by our National Institute of Environmental Health Sciences (NIEHS) Center Grant, aims to explore the biochemical and vascular basis of this increased diabetic susceptibility to air pollution’s effect(s) on cardiovascular health.

Although the acute cardiac events of concern are thankfully rather rare for any individual, we hypothesize that the fundamental electrical and biochemical changes underlying a propensity for blood to clot (as in MIs) or for the heart to have abnormal rhythms will be much more common. By studying specific blood and blood vessel markers and electrocardiograms (EKG) before and after exposure to pollution, these subclinical changes can be observed. If confirmed, we can be more confident of the pathway(s) by which air pollution may cause clinical events.

Because the epidemiologic literature suggests that increases in cardiovascular outcomes (i.e. MI, stroke, arrhythmias, exacerbation of congestive heart failure) may follow increases in particle air pollution over time frames as short as 2-24 hours, we have developed a research paradigm of having subjects breathe increased amounts of pollution for 1-2 hours and then following their biochemical and EKG responses for the next 24 hours, looking for subtle changes in blood clotting, blood vessel function, and heart rhythm, among others. In the present study, rather than use our standard laboratory source of pollution (diluted engine exhaust in a controlled environment facility), we opted for a real-world exposure: the New Jersey Turnpike’s truck lanes during morning rush hour.

Figure 1. The figure shows levels of particulate air pollution mass (PM2.5), ultrafine particle counts (UFP), and carbon monoxide (CO) from 8:45am until 10:10 on one day of our experiment. It demonstrates how air pollution particle mass doubles during the time on the turnpike and the number of ultrafine particles rises to a maximum increase of 8-fold over the baseline at our labs in Piscataway. We do not yet have data on what the effects of these increased pollution levels are on the outcomes we are measuring.

Under the direction of Dr. Junfeng (Jim) Zhang, chair of environmental and occupational health at UMDNJ School of Public Health, we are measuring pollution exposures including the fine particle mass concentration, potentially potent ultrafine particles, as well as pollutant gases such as carbon monoxide and nitrogen dioxide, contrasting the Turnpike to the relatively lower levels in Piscataway. Endpoints measured before and after the drive on each subject are vascular reactivity (endothelial function), blood nitrite and nitrate, the blood coagulation proteins von Willebrand Factor and Endothelin-1, as well as stored specimens to later examine changes in gene expression and the ubiquitin proteasome pathway. Our study subjects include a projected 22 type II diabetics, of whom 14 have completed their 2 hour ride on the Turnpike and provided various specimens.

This project represents translational research at UMDNJ and Rutgers. We have recruited type II diabetic subjects from the clinics of UMDNJ-Robert Wood Johnson Medical School (RWJMS) with the cooperation of endocrinologists Louis Amorosa and Stephen Schneider. Not only are we leveraging our own resources in the EOHSI Clinical Research Division and the UMDNJ-School of Public Health to care for and sample the subjects, but Dr. Robert Laumbach of EOHSI oversees the sophisticated analysis of the EKGs (heart rate variability). We also have available the laboratory resources of: Dr. Andrew Brooks and the EOHSI Biomarker Facility for handling and storing blood samples; Dr. Andrew Gow in the Rutgers School of Pharmacy for performing state of the art blood nitrite assays (a metabolite of the vasodilator nitric oxide which we hypothesize will be decreased by traffic); and Dr. Kiran Madura in the RWJMS Department of Biochemistry for the proteasome assays. Thus, this represents collaboration between many types of scientists, who have identified a public health problem of particular importance in New Jersey, and responded by creating an organized interdisciplinary field study.

We are using similar collaborative models (environmental physician/epidemiologist-exposure scientist-basic science/support laboratory-treating clinician) in various combinations on multiple air pollution projects from Piscataway to Beijing. This is one of two ongoing studies focusing on susceptibility in diabetics, the other being a study of whether pre-existing diabetes and chronic obstructive pulmonary disease may modify the effect of specific types of particulate air pollution on the risk of MI. A new project of particular interest is a study directed by exposure scientist Jim Zhang, which will examine the changes in similar biomarkers in Chinese medical students before, during, and after the 2008 Olympics in Beijing. It is expected that particulate air pollution will be reduced in Beijing by approximately 60-70% for six weeks during the 2008 Olympics, thus providing a rare opportunity to examine the change in these biomarkers following both rapid decreases (from before to during the Olympics) and then rapid increases (from during to after the Olympics) in air pollution. This study will exclude diabetics, but the lessons we are learning in the current study will help to inform our approaches next year in China.

Results from the Turnpike diabetes study are expected early in 2008.

Howard M. Kipen earned an MD in 1979 from the University of California-San Francisco and an MPH in 1983 from Columbia University. He is a professor of environmental and occupational medicine at UMDNJ-Robert Wood Johnson Medical School (RWJMS) and UMDNJ-School of Public Health (SPH), and chief, Clinical Research and Occupational Medicine Division, at the Environmental & Occupational Health Sciences Institute (EOHSI), a collaboration of UMDNJ and Rutgers. His research has focused on controlled exposure studies of air pollutants, inflammation and cardiovascular disease models, biopsychosocial models of disease, World Trade Center symptomology, and Gulf War Syndrome.

David Q. Rich earned an MPH from SPH in 1999 and a Doctor of Science from the Harvard School for Public Health (HSPH) in epidemiology and environmental health in 2004. After post-doctoral fellowships at HSPH and Brigham and Women’s Hospital, he returned to SPH as an assistant professor in the Department of Epidemiology in 2005.