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Pioneering research aims to identify the cause of diabetes: CU Denver's Barbara Davis Center is working to end type 1 diabetes one child at a time.

One of the first things Amy Lyden learned about her son Caleb was that he might develop diabetes. After being told at the hospital that Caleb had a gene marker putting him at a slightly higher risk of contracting the disease, she enrolled the newborn, now 3, in a global study called TEDDY.


Comprised of six groups of research physicians from Germany, Sweden, Finland and the United States, TEDDY (The Environmental Determinants of Diabetes in the Young), has researched the causes of Type 1 diabetes since 2004 by monitoring children who have certain gene markers from birth onward.

Managed locally by the Barbara Davis Center for Childhood Diabetes on the University of Colorado Denver Anschutz Medical Campus, the TEDDY study was piggybacked on pioneering research the center has conducted since 1993. For the past 15 years, the center's DAISY study (Diabetes Autoimmunity Study in the Young) genetically typed more than 30,000 newborns in Colorado; the TEDDY study plans to type 350,000 children worldwide.

The largest diabetes and endocrine care program in Colorado, the Barbara Davis Center treats about 80 percent of the state's children with Type 1 diabetes. With clinical and basic researchers working side-by-side with a large patient population, the center is at the forefront of research designed to predict the disease, identify its causes and understand how to prevent it.

Lyden says she was definitely anxious when she learned Caleb's diagnosis but never had any real fears, a fact she attributes largely to the family's positive experience with the study and the researchers.

"Although Caleb's risk has increased a little bit, that doesn't mean he will develop diabetes," Lyden says. "But if he does, by participating in this study we'll be able to catch it early."

More than 17 million people in the U.S have been diagnosed with diabetes at an estimated cost in 2007 of $174 billion, according to a recent report from the American Diabetes Association. Of those diagnosed, between 5 percent and 10 percent have Type 1 diabetes, the more serious form of the disease. Traditionally referred to as "childhood diabetes," although people of any age are susceptible, Type 1 diabetes is an autoimmune disease that causes pancreatic cells to be destroyed, eliminating the body's ability to make insulin.

By studying gene markers, or autoantibodies, like that found in Caleb's blood, researchers can better predict who will develop the disease and when.

"If we can pinpoint when the baby's switch is turned on and the immune system starts killing insulin cells, then we are in a better position to know what environmental factors could be incriminated as potential triggers," says CU Health Sciences professor Marian Rewers, the center's clinical director and the principal investigator of the DAISY and TEDDY studies.

Rewers says they've discovered if a baby develops just one autoantibody to insulin-making cells, the risk of developing Type 1 diabetes increases about 50 percent; with two autoantibodies, the increase is close to 100 percent.

Three of those autoantibodies have been well-known for more than a decade; a fourth, a zinc transporter called ZnT8, was recently identified by another CU Health Sciences professor, John C. Hutton, who is also the research director for the Barbara Davis Center. The first new autoimmunity target discovered in 10 years, ZnT8 makes up two of three research projects that received $5 million in funding over the next five years from the Juvenile Diabetes Research Foundation.

"That's what's keeping us very busy these days," Hutton says. "The zinc transporter has special importance as it binds to the insulin molecule. By some mechanism we don't understand, the immune system somehow perceives this molecule as being different and destroys the cells which normally would happily produce insulin."

Hutton says the goal is to break the "vicious cycle of autoimmunity and tissue destruction" by identifying a therapy that's specific to Type 1 diabetes and then deliver it to those at high risk. Researchers have already proved they can do this in experimental animals, but Hutton acknowledges it is a long way off for humans.


"Our dream would be to administer a magic bullet of sorts," Hutton says. "If we could identify those at risk and provide some sort of vaccination we can actually prevent it, if we can identify (the diabetes marker) early enough before there's much damage done. By the time patients have clinical manifestations they've lost 90 percent of their cells that produce insulin."

Dr. George Eisenbarth, executive director of the Barbara Davis Center, says a major goal is to change the treatment so that patients can control diabetes without even having to think about it. One new way is via continuous glucose monitors, which free diabetes sufferers from constant needle pricks to check blood sugar levels. Several hundred of the center's patients are testing the monitors, which consist of a tiny needle implanted under the skin that communicates wirelessly to a handheld device that tracks the insulin level.

"One patient testing the sensor plays hockey; his mother monitors him while he's out on the ice," Eisenbarth says. "The technology has changed, and with it came better insulin and better devices."

For children like Owen Woessner those new technologies may allow him to lead a more normal life than ever thought possible. Screened at birth two years ago through TEDDY, Owen was found to have less than a 1 percent chance of developing the disease. Yet just a year later, Owen was rushed to the emergency room with a blood sugar level of 900.

"We didn't think he was going to make it," his father Trey Woessner says. "But he's a tough little guy."

Woessner says it has been hard on Owen since being diagnosed; often he's confused by all the doctors, shots and needles he has to deal with on a constant basis. But his son has the advantage over kids diagnosed in their teens who have to drastically change their lives, he says: Owen will never know anything different.

"It's not the lottery we wanted to win," Woessner says. "Sometimes I am still beside myself, and some days are harder than others. But Owen is such a fantastic, special kid; he can do everything anybody else does."

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Comment:Pioneering research aims to identify the cause of diabetes: CU Denver's Barbara Davis Center is working to end type 1 diabetes one child at a time.
Author:Cole, Rebecca
Geographic Code:1USA
Date:Apr 1, 2008
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