Chemicals May Increase Diabetes Risk, Not Just Genes, Weight and Exercise

Chemicals in the water, soil, or buildings around you could be upping your risk of developing diabetes, according to new research from Stanford University.

While genetics, diet and weight all feed into one's chances of getting adult-onset (type II) diabetes, these factors can only explain a portion of the risk -- environmental risk factors may offer a deeper understanding of why people develop the disease.

Using a new technique which mimics the way scientists mapped the human genome, researchers were able to identify three environmental elements that are correlated with an increased risk of type II diabetes: a pesticide called heptachlor epoxide; the banned chemical PCBs, used in adhesives and machinery; and -- surprisingly -- a form of vitamin E.

"Since the genome project was finished, a lot of people have been excited about the genetic causes of disease, but I don't think most people realize that the environmental factors for many things are actually stronger," says bioinformatics expert Dr. Atul Butte, a co-author of the study.

Building on the same techniques scientists use to map disease risk over many genes, bioinformatics graduate student Chirag Patel conceived and designed a computer program that could map risk over hundreds of environmental factors, such as chemical toxins found in the soil, water, and industrial products around us.

"We were hoping to find targetable environmental factors for diabetes," Butte says, "and it looks like that's what we've found."

The research is still in its early stages, Butte and Patel caution, and these three chemicals are by no means proven to cause diabetes, but the new technology opens doors for future research in this area.

The study was published Wednesday in the online journal PLoS ONE.

Looking for Chemical Culprits

Linking things in the environment with risk of disease is a common practice for epidemiologists, but it's difficult to run analyses for many factors at once. Patel's new system, called Environment-Wide Association Studies -- EWAS for short -- makes sorting hundreds of environmental elements possible.

"It's clear that type II diabetes has a large environmental component," says Dr. Christopher Saudek, a diabetes specialist and professor of medicine at John's Hopkins University. He says that the studies looking for a genetic link to the disease have been largely disappointing. One gene consistently comes up, but even that explains a relatively small amount of the risk, he says.

Given that the genetic links leave much of diabetes risk unexplained, tools like EWAS may help bridge the gap between the risk explained by genes and behavior and environmental risk, Saudek says.

Banned Toxins Resurface

Drawing from nationally-representative data from the Centers for Disease Control and Prevention, the researchers were able to assess the association between type II diabetes and 266 different environmental factors. After adjusting for age, sex, ethnicity, and body mass index, the three factors still stuck out as strongly correlated with the disease.

Pesticides, toxic chemicals, and a form of vitamin E were associated with a higher likelihood of type II diabetes in Wednesday's study.

Finding an association between an antioxidant like vitamin E and diabetes was unexpected and a bit puzzling, Butte says, but it's not particularly surprising that the chemicals showed up in the analsysis.

The specific pesticide and chemical identified by the study have a long history of toxicity and negative health effects.

Polychlorinated byphenyls, often referred to as PCBs, raised public health suspicions as early as the 1930s. Later research linked PCBS to a number of health risks, including liver cancer, and the production of PCBS was banned in the U.S. in 1979. In certain "closed" applications, PCBS are still used today, however.

Similarly, heptachlor epoxide, the pesticide identified by the study was one that was banned in the 1980s because of its toxic impact on humans, Butte says, but remnants of the chemical remain in the soil on locations where it was used heavily.

Though these two chemicals were not previously associated with diabetes, Dr. Philip Landrigan, professor and chairman of Community and Preventive Medicine at the Mount Sinai School of Medicine, says it may be in line with growing research to think that toxic chemicals like these could affect diabetes.

"The basic notion that certain chemicals can predispose people to obesity is becoming more and more believable as the research progresses," says Landrigan, adding taht given the tight connection between obesity and type II diabetes, these chemicals may be likely suspects for increasing environmental risk.

Hope for Future Risk-Assessment

But Patel cautions that while EWAS is useful for research purposes, the environmental ingredients identified by EWAS do not prove a direct link between diabetes and these chemicals. "These are very strong associations, but they're still just associations," he says, not causal links.

It could be that those who already have type II diabetes are more likely to come into contact with the elements identified, either through medication, diet changes, or supplements (especially in the case of vitamin E), Butte points.

Also, the chemicals identified are all fat-soluble, "meaning that they tend to live in our bodies in fat tissue," Patel says, so it could be that because those with type II diabetes are more likely to be overweight, they are more likely to have stored greater concentrations of these chemicals in their fat.

Nonetheless, these EWAS is a powerful tool for pointing researchers towards possible environmental causes, says Dr. Marcel Casavant, chief of pharmacology and toxicology at Ohio State University.

"This is a whole new way to explore possible environmental factors," he says. "Now we know if we want to look into possible causes of type II diabetes, we need to look at these [three factors]."

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