Diabetes: Contribution Of Toxins In The Body

Unraveling how toxins contribute to disease has long been a murky matter. Now researchers at the Stanford University School of Medicine have developed a quick new method for figuring out which foreign chemicals in the body coincide with complex diseases, and used it to examine the increasingly prevalent type 2 diabetes.

"The whole inspiration was to do for the environment what has been done for genetics," said Atul Butte, pediatrician and computer scientist at Stanford Medical School and an author of the study published online Thursday in the open-access journal PLOS One.

To find potential genetic causes of a disease, researchers typically look for genetic markers common to people with the disease but rare for others. Instead of testing for one genetic marker at a time, they search for any such traits.

The new method, developed by Butte, his graduate student Chirag Patel, and Stanford professor of medicine Jayanta Bhattacharya, mimics that approach for environmental factors.

Using data collected by the Centers for Disease Control and Prevention, the team correlated each anonymous test subject's fasting blood sugar level — a sign of type 2, or adult onset, diabetes — with the levels of 266 chemicals detected in blood and urine. The CDC tested people from different age groups and ethnic backgrounds to gauge the overall health of children and adults.

"The data's just been sitting there, waiting for an analysis like
this," Butte said. "Every day we encounter something new, but we still don't know what this means for our health," Patel said.

Environmental factors

The method has several challenges that genetic testing does not, which makes it difficult to clearly establish cause and effect. For instance, a disease can be the reason certain toxins accumulate in the body instead of those toxins being among the causes of the disease. Also, the CDC tests only for compounds that are stable in blood and urine, but misses thousands of compounds that disintegrate quickly.

Still, using the new method, researchers uncovered several chemicals of interest for type 2 diabetes. Surprisingly, a form of vitamin E found in oil and nuts — gamma tocopherol — was related to elevated fasting blood sugar levels. And higher concentrations of polychlorinated biphenyls, pollutants banned in the United States in 1979, often coincided with higher fasting blood sugar levels. Some PCBs have previously been linked to type 2 diabetes.

"It's reassuring that we found some correlations that we were expecting to find," Butte said. But "there were many more surprises than reassurances."

The method also found similar results for heptachlor epoxide, a chemical that animals and plants derive from an insecticide that was banned in the 1980s.

Heptachlor persists in the water and soil, can accumulate in the tissues of animals, and can be passed from mothers to infants through breast milk.

Much testing remains before the researchers can establish which environmental factors cause or deter type 2 diabetes.

"Before we start telling people what to eat, which plastic bottles to throw away, I would like to see these things replicated," said Mark Cullen, a professor of internal medicine at the medical school who has worked with Patel.

Valuable Approach

Next, the team hopes to reproduce the type 2 diabetes results in another independent population. The next step after that will be to track people with elevated levels of gamma tocopherol and heptachlor epoxide to see whether they develop diabetes. The long-term payoff for the method will one day allow medical science to search for environmental risk factors for other complex diseases, such as obesity, heart disease and cancer.

"This is a very valuable first approach," said Rochelle Long, program director of the National Institute of General Medical Sciences (NIGMS), which supported the research. "It will need to be replicated. One caveat is that you can only discover factors that are present in the data set to begin with."

In addition to NIGMS, the work was funded by the National Library of Medicine, the National Institute on Aging, the Lucile Packard Foundation for Children's Health and the Howard Hughes Medical Institute.

The CDC survey is a laborious task that involves running a battery of tests on each subject. Patel and Butte hope to inspire California biotech companies to develop new chips for quickly testing for hundreds of relevant compounds. Studying environmental factors in disease is a more uplifting task than studying genetic factors, they said.

For instance, the factors most highly linked to type 2 diabetes that their method uncovered have already been banned.

"The public can make a difference," Butte said. "Genes — you can't do anything about those."

Thank you Olga Kuchmen/Mercury News