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Friday, March 7, 2003

Seattle researcher examines environmental causes for juvenile diabetes

By CAROL SMITH
SEATTLE POST-INTELLIGENCER REPORTER

The trend is disturbing: Juvenile diabetes, a disease that can cost people their kidneys, their eyesight, even their limbs later in life, has been steadily claiming more victims during the past few decades.

And no one knows why.

While the rate of adult-onset diabetes has also been going up, that's easier to figure out. Our super-sized, couch-potato culture is making people heavier, a known risk factor for diabetes in adulthood.

But juvenile diabetes is a different story. Although scientists have sorted out a number of the genetic factors responsible for putting kids at risk, they believe at least half the chance of getting diabetes is related to the child's environment.

		Paul Joseph Brown / P-I
	Dr. Bill Hagopian of the Pacific Northwest Research Foundation received a $5 million grant to study environmental factors causing juvenile diabetes.

"It can't just be genes," said Dr. Bill Hagopian, a researcher with the Pacific Northwest Research Foundation in Seattle. The number of children diagnosed with the disease has been increasing about 3 percent a year since 1980, he said.

Hagopian recently received a five-year, $5 million grant from the National Institutes of Health to help conduct the first large-scale attempt to discern the environmental factors that cause one kid to get juvenile diabetes, and another to grow up unscathed.

If successful, it could lead to potential ways to prevent or cut down on the disease, which affects about 1 in 300 children, and costs billions in U.S. health dollars every year.

It could also serve as a model approach for unraveling the intricacies of genetic-environmental interactions in many other chronic diseases.

"Cancer is a great example of a disease where there is clearly genetic predisposition . . . but also many environmental causes," Hagopian said.

But environmental contribution to disease is notoriously difficult to study, in part because it relies on study participants keeping laborious, detail-oriented diaries. And until recently, it was impossible to separate the contribution of underlying genetic differences.

Hagopian, however, had an idea for a way to get around that problem.

He went to a vast, untapped database locked away in state Health Department file cabinets. That data, based on "blood spots" banked from newborn heel sticks, contains the genetic codes of all the babies born in Washington since the 1960s. The blood samples were initially taken to screen for metabolic disorders, such as sickle-cell anemia.

Two years ago, Hagopian contacted a half-million Washington families to ask whether he could test their children's blood spots for the genes thought to contribute to diabetes. That study, which ended up testing about 32,500 samples, proved the feasibility of identifying high-risk kids using blood spots. He hopes to use a similar approach to identify a new group of about 300 high-risk babies to follow for the long-term study.

As many as 20 genes are linked to juvenile, or Type 1, diabetes, although two in particular seem most strongly linked. The combination of genes you wind up with in the genetic lottery determines your risk.

But it's a sliding scale.

Even having the riskiest assortment of genes -- a combination that affects about 17 percent of the population -- is no guarantee of getting the disease. Only one in 80 of these children will come down with the disease. The question is which ones.

Once Hagopian identifies a group of high-risk children, he hopes to follow them for at least five years, and hopefully longer, to see which develop the disease. The highest incidence of juvenile diabetes occurs around age 12, so the researchers hope to follow the kids that long.

They are still designing the research parameters and don't expect to begin recruiting families to participate in the study until the fall. Families would keep food diaries and children would have to provide periodic blood and stool samples to track various exposures.

In addition to Seattle, the study will involve children in five other clinical centers in the United States, Germany, Sweden and Finland.

The overall goal is to identify strategies to keep children from getting diabetes.

"What if you could, say, avoid rutabagas and coxsackieviruses," Hagopian said. "What if those two things alone reduced disease by 80 percent?"

Researchers are still deciding which environmental factors to track, but they have some leads.

"We think early exposure to non-breast milk proteins, especially those in cow's milk, may play a role," he said. "And gluten (a protein found in wheat). It's very clear if babies are exposed to gluten in the first three months, you have a much higher risk." Infants could be exposed to gluten in formula.

Some preliminary studies indicate the risk increases five-fold.

In addition, there is some evidence that exposure to Vitamin D, certain fatty acids, and some common gastrointestinal viruses, such as the coxsackievirus, may be linked to development of diabetes.

Scientists believe it's something about early exposure that conditions the body to get the disease. For example, about one-third of children born to mothers who had German measles while pregnant end up with diabetes.

"That tells you an exposure even as early as the womb can predispose to diabetes," Hagopian said.

Jamie Harmon of Seattle, mother of a 4-year-old who had his blood spot tested, is hoping the information will eventually lead to better treatment for diabetes, or prevent it altogether.

She doesn't know her son's results yet, but said she would be more likely to catch early signs of the disease if she knew her son was genetically predisposed to getting diabetes.

Although there's no history of juvenile diabetes in her family, she has a Scandinavian heritage, and Scandinavian countries have a higher incidence of Type 1 diabetes.

"The more information you have about it, the sooner you can take action," she said.

Harmon, a diabetes researcher herself, has seen the ravaging effect the disease can have.

"A lot of people think you just take some insulin and you're fine," she said. "But it's a nasty disease."

P-I reporter Carol Smith can be reached at 206-448-8070 or carolsmith@seattlepi.com

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