Chronic Disease: The Next Generation of Prevention Research

Winter 2007

While we have made great strides in health, chronic diseases—such as heart disease, cancer, and diabetes— remain the leading cause of death worldwide. In the United States, these diseases account for 7 of every 10 deaths and affect the quality of life of 90 million Americans. According to the World Health Organization (WHO), chronic disease is responsible for 60 percent of all deaths worldwide, and 80 percent of those deaths occur in low- and middle-income countries.

Although chronic diseases are among the most common and costly health problems, they are also among the most preventable. The major risk factors for chronic disease are an unhealthy diet, physical inactivity, and tobacco use. If these risk factors were eliminated, at least 80 percent of heart disease, stroke, and type 2 diabetes would be prevented, and 40 percent of cancer would be prevented, according to the WHO.

Building on Tradition

Experts at the University of Minnesota School of Public Health are building on a rich tradition of innovative, populationfocused research aimed at reducing chronic disease. SPH founding faculty member Ancel Keys was one of the first researchers ever to link behavior and diet to heart health. That work landed him on the cover of Time magazine in 1961. Emeritus professor Henry Blackburn, who studied under Keys, directed the first and formative years of the school's Division of Epidemiology. The division quickly made a name for itself for conducting pioneering work in cardiovascular disease prevention. Today, the SPH is known for leading some of the world's largest and longestrunning epidemiologic studies that have been critical in identifying key risk factors for heart disease, cancer, and other chronic culprits.

The Iowa Women's Health Study is one such project. Led by SPH professor Aaron Folsom, the study started in 1986 with a cohort of 41,836 postmenopausal women aged 55-69. The study goals are to determine how body fat distribution, diet, and other lifestyle factors predict cancer in older women. The research has led to more than 200 published articles. Just a few recent findings indicate the spectrum of information to come out of this one study: hormone replacement therapy does not increase risk of leukemia; magnesium can reduce risk of colon cancer; and, prevention of weight gain before menopause reduces risk of postmenopausal breast cancer. While the findings are vast in scope, the foundation of the Iowa Women's Health Study is that it seeks to understand what leads to cancers and therefore how to prevent them. The project plays a key role in identifying risks of cancer in older women.

Genetic Clues

Genetic research is fast becoming the next frontier for chronic disease prevention. SPH associate professor James Pankow works in the area of molecular and genetic epidemiology to determine the causes of type 2 diabetes and cardiovascular disease. One of his current projects analyzes biomarkers and proteins in the blood of a group of adults, some who have developed diabetes over the course of the study. Pankow and colleagues are able to analyze blood samples taken before the study participants developed diabetes, which helps the researchers to pinpoint the proteins that may lead to disease. His team found proteins related to inflammation in the blood of participants who later developed diabetes. The discovery lends support to a growing hypothesis that links inflammation to diabetes. The researchers also found lower levels of the protein adiponectin, which is produced by fat cells and released into the blood. As body weight goes up, adiponectin levels go down. The protein plays a key role in suppressing metabolic processes that lead to type 2 diabetes. The adiponectin findings strengthen the connection between obesity and diabetes.

"It's unclear why obesity puts you at risk for diabetes," says Pankow. "This protein might help to explain that link."

SPH faculty in the Division of Biostatistics have been teaming up with colleagues across the University to discover the genes behind a host of chronic diseases. SPH assistant professor Tracy Bergemann is working with colleagues in the Medical School on a first-of-a-kind study on osteosarcoma, the most common type of bone cancer. The research team has singled out 30 genes related to bone growth, and Bergemann is using complex statistical models to determine which of them are significant in their connection to osteosarcoma. SPH assistant professor Cavan Reilly has searched for the genetic basis of asthma by analyzing DNA samples from 27 families who each have at least two asthmatic members. Using a statistical model he designed, Reilly has been able to track down a gene that shows strong associations to asthma.

Environmental Culprits

How the environment interacts with genes to lead to chronic disease is the focus of research from faculty in the school's Division of Environmental Health Sciences (EnHS). "We believe in the ‘envirome,'" says EnHS head William Toscano. The concept behind the envirome is that whatever is not genetic is environmental. The envirome includes socioeconomic status, behavior, lifestyle, nutrition, pollutant chemicals, environmental toxicants, and how individuals interact with each other.

Much of this envirome-focused work investigates the effects of POPs (Persistent Organic Pollutants). Two wellknown POPs are dioxins and PCBs (polychlorinated biphenyls). These chemical substances, which typically accumulate up the food chain, may be linked to cancer and other chronic conditions. SPH associate professor Jeff Mandel is investigating the relationship between POPs and diabetes mellitus. Previous studies have indicated the link, but haven't demonstrated whether the relationship is cause and effect or simply coincidental. But some studies have shown that higher exposure to POPs leads to more severe diabetes. "That's the intrigue," says Mandel. He thinks one of the next steps should be to look at POPs in relationship to a lab assessment of the metabolic changes of diabetes in an effort to better understand the biologic impact that these pollutants may have.

Over the past 20 years, rates of asthma have skyrocketed, but researchers still aren't sure why. SPH associate professor John Adgate is working with teachers in the Minneapolis public school system on the Home Allergen Reduction Study. The teachers have acted as liaisons between the researchers and the children's families. Many of the families in the study live in older homes and rental properties, where mold and other contaminants are a concern.

"One of the places where we are most exposed to pollutants is in our own homes," says Adgate. "The levels of certain pollutants are, in some cases, higher in your house than they are elsewhere." Home pollutants are associated with asthma but the nature of the association is, according to Adgate, "one of the unsettled questions related to the great asthma epidemic that we're going through now."

New Methods

SPH professor Brad Carlin is leading an innovative approach to research in which statistical tools are applied to geographically referenced data. The results are "disease maps" that can clarify underlying spatial patterns in disease—a vital tool in planning future public health interventions. Carlin was called in to refine the numbers of people at risk for radon exposure in a project conducted by the Centers for Disease Control and Prevention. The CDC was trying to estimate the number of deaths attributable to lung cancer in families living near a uranium recycling plant in southwestern Ohio. It was easy to determine which people had been exposed to harmful levels of radon some 25 years ago, but it became much more difficult to determine whether that exposure had led to lung cancer.

"We were able to find improved risk estimates but could not get reliable death data," explains Carlin. "So there was an important piece of the puzzle missing." A legal case between a local citizen's group and the federal agency charged with cleaning up the plant was eventually settled out of court.

SPH professor Robert Kane, Minnesota Chair in Long-Term Care and Aging, is heading up a collaboration between the Division of Health Policy and Management (HPM) and the Division of Epidemiology and Community Health (EpiCH). HPM faculty include Rosalie Kane and Karen Kuntz. EpiCH faculty include Deborah Hennrikus, Rhonda Jones-Webb, and Kim Robien. The group's aim is to develop chronic disease prevention strategies that are effective in changing individual behavior and reducing costs in health care delivery. The researchers plan to develop a model that would predict the effectiveness of specific strategies for controlling blood pressure, managing osteoporosis, and addressing other chronic diseases.

While it may seem like common sense that too much fast food is bad for you, there has been surprisingly little scientific evidence linking fast food diets to health status. In the first comprehensive, long-term study of its kind, SPH associate professor Mark Pereira has linked fast food consumption to type 2 diabetes. Researchers tracked the dietary habits of more than 3,000 young people for 15 years. They found that those who ate at fast food restaurants at least twice a week or more and further increased their fast food over time gained about 10 pounds more than those who ate fast food less than once a week and further decreased their fast food over time. They also found that frequent fast food consumption doubled one's increase of a pre-diabetes condition known as insulin resistance.

On the heels of these findings Pereira set out on a pilot study to determine the effects of fast food consumption in the short term. He tracked 15 obese adults for three months. For the first month, the participants ate their usual diet and gained about one third of a pound on average. For the second month, participants ate at restaurants twice a day and gained about two thirds of a pound. For the third month, the group was supplied with groceries that fell within dietary guidelines. They ate every meal at home and gained no weight. Pereira is using the findings to apply for funding to follow 360 people for a year. The study would compare two strategies: counseling frequent restaurant-diners on how to order healthy options and counseling people who would eat only at home. The researchers would also track risk factors for diabetes and heart disease. The project is one of the first to address both the issues of individual responsibility and environmental pressure that surround the obesity crisis.

"Most of the emphasis in research has been on the individual," says Pereira. "But there's a tremendous amount of environmental pressure, with portion sizes and choices at restaurants."

New Populations

As the burden of chronic disease moves to developing countries, SPH experts are forging international partnerships in an effort to improve health. The SPH has signed an agreement with the Indian Council of Medical Research (the equivalent of our National Institutes of Health) to partner on translational and clinical research. The partners are designing a study that will compare bariatric surgery and diet and lifestyle changes as approaches to deal with obesity and type 2 diabetes. The trial includes the University of Minnesota and three clinical sites in India. SPH professor John Connett is the lead biostatistician on the project and will be responsible for collecting and analyzing all data associated with the study.

SPH professor Gurumurthy Ramachandran is in the fifth year of investigating how air quality in India affects the lung health of women and children. Identifying the causes of chronic respiratory illnesses in India isn't difficult. Poorly ventilated homes are filled with dirty fuels for heating and cooking. An explosive growth in industry and streets jammed with vehicles contribute to outdoor air pollution. But alarmingly little research has been done to address the problem. By providing scientifically sound data on exposure and lung health, Ramachandran hopes policies might be crafted that would improve air quality in developing countries like India.

SPH researchers are partnering with community members to reduce exposure to contaminants found in local fish for Minnesota's Dakota and Ojibwe populations. Many of the fish that these populations eat more than once a week are contaminated with mercury, dioxin, and PCBs. Dioxin and PCBs are known to cause cancer. The project team includes environmental health faculty Bruce Alexander, Pat McGovern, and William Toscano, research associate Sara Axtell, pediatrics assistant professor Anne Kelly, and community partner Lea Foushee, co-founder of the North American Water Office. Foushee has put together materials on which Minnesota fish are safe and unsafe to eat, how to clean fish to reduce exposures, and why pregnant women and small children are especially sensitive to exposure. The hope is to distribute the materials to tribal members so that they can reduce their exposure to the contaminants.