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A new blueprint to aid physicians in predicting risk for type 1 diabetes


Undiscovered protein may help identify those whose disease will progress rapidly

Researchers have discovered a combination of tests that can more accurately predict who will develop type 1 diabetes. In the process, they’ve also uncovered signs of a new protein that may forecast a more rapidly developing form of the disease. Together, these findings could help researchers screen patients for clinical trials that eventually may lead to a vaccine or cure for type 1 diabetes.

"We can’t use a vaccine to prevent type 1 diabetes in the general population, like we do for polio, because we don’t know if the vaccine will cause harm or effectively prevent the disease. So we have to identify people at risk first," said Massimo Pietropaolo, MD, a researcher in the Diabetes Institute at Children’s Hospital of Pittsburgh. "Our study and the new research it leads to will help us better predict risk of type 1 diabetes and identify those who can be involved in major trials in the United States and around the world."

Dr. Pietropaolo, who also is an associate professor of pediatrics, medicine and immunology at the University of Pittsburgh School of Medicine as well as an associate professor of epidemiology at the Graduate School of Public Health at the University of Pittsburgh, spoke today at an American Medical Association briefing, Diabetes: Understanding & Advancements, in New York City. He and other researchers from Children’s Hospital of Pittsburgh and the University of Pittsburgh began their study, to be published in the December issue of the journal Pediatric Diabetes, by looking at both older and newer methods of assessing risk for type 1 diabetes in family members of those with the disease.

Older assays, or chemical tests, predict risk for type 1 diabetes by identifying what are called islet cell antibodies. These are produced when the body’s immune system fails to recognize insulin-generating islet cells produced by the pancreas as self, and attacks them as if they were foreign cells. The islet cell antibodies are markers of an attack on the insulin-producing islet cells of the pancreas by the body’s own white cells (T cells) as if the islet cells were outside invaders, thereby decreasing the body’s ability to produce the insulin that helps cells convert sugar into energy.

Newer tests use biochemical markers to detect islet autoantibodies, and these autoantibody responses signify a cause and effect relationship between type 1 diabetes and autoimmune phenomena targeting pancreatic insulin-producing cells. "In the mid 1990s, we found that a combination of autoantibodies could predict type 1 diabetes over time in individuals at risk of developing type 1 diabetes," Dr. Pietropaolo said. "However, there were some patients who were positive for a combination of these biochemical markers but still did not develop type 1 diabetes."

Anytime a marker is used to predict disease, there is some margin of error. But Dr. Pietropaolo and his coauthors wondered if they could do better and if the older assay held the key. In the new study, they looked at both levels of islet cell antibodies and biochemical markers of autoantibodies in 1,484 first-degree relatives of people with type 1 diabetes.

Those who tested positive for the two most commonly recognized autoantibodies had a 14 percent risk of developing type 1 diabetes after 10 years. However, those who displayed those two autoantibodies along with islet cell antibodies had an 80 percent risk after just 6.7 years. "The surprise was that by using these older assays in combination with the newer tests, we were able to more accurately predict type 1 diabetes in the family members of those with type 1 diabetes," Dr. Pietropaolo said.

In addition, family members with a certain subtype of islet cell antibody developed type 1 diabetes after fewer years than others. The study authors suspect that this antibody subtype is recognizing and attacking a previously unknown protein associated with insulin requiring diabetes.

"We now have the tools to predict type 1 diabetes, particularly in relatives of type 1 diabetic patients," said Dr. Pietropaolo. "This paper also opens up a lot of research in the future to identify this new marker associated with rapid progression to type 1 diabetes." Work is now under way in Dr. Pietropaolo’s lab to determine exactly what the new protein is and how it may cause the disease to advance more quickly.

Marc Lukasiak | EurekAlert!
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