Childhood Diabetes Starts Early, New Test Shows

From the WebMD Archives

Feb. 7, 2000 (Atlanta) -- A new test helps predict childhood diabetes. According to studies published in February's Proceedings of the National Academy of Sciences, the test shows that diabetes, caused by immune defects that destroy insulin-producing cells, often begin in the first year of life. This may make it possible in the future to start therapy to prevent the disease before it has a chance to develop.

"I think that childhood diabetes is predictable," lead investigator George S. Eisenbarth, MD, PhD, tells WebMD. "We didn't know how early the immune system had locked in the destructive pathway that leads to diabetes."

Childhood diabetes appears to be linked to specific genetic defects. Children with a diabetic parent or sibling are 25 times more likely to develop diabetes than the average child, Eisenbarth's colleague, Marian Rewers, MD, PhD, tells WebMD. Ten percent of these children inherit a particularly dangerous diabetes gene, and half of them get diabetes by the time they are five years old. But an early warning sign, antibodies that attack a person's own cells or proteins -- called autoantibodies -- appear even earlier.

Tests for two other types of diabetes-related autoantibodies, called GAA and IA-2, have been available for at least seven years, Eisenbarth says. The new test now makes it possible to test for a third type of autoantibody -- called anti-insulin antibodies -- and suggests that these are the first to appear. "In young kids we usually see insulin antibodies first," Rewers says. "It is hard to pinpoint as we don't test every day. But from our data it seems anti-insulin antibodies are very important."

Eisenbarth and co-workers at the Barbara Davis Center for Childhood Diabetes at the University of Colorado in Denver began testing 934 young children at an average age of nine months: 131 close relatives of a type 1 diabetes patient and 803 children from the general population. Type 1 diabetes is the form of the disease that develops most often in children.

Of five children found to have the anti-insulin antibody before their first birthday, four developed diabetes by age three and a half -- and the fifth child is not yet two years old. Only one of the 929 children who initially tested negative for the antibody developed diabetes -- and this child tested positive at his second visit, shortly after reaching age one.

A particularly exciting finding came when Eisenbarth and colleagues used the test in a type of mouse that develops diabetes. Nearly all of the mice with the anti-insulin antibodies rapidly developed diabetes, but this happened in only one mouse without the antibody. "[Most people thought] that mice don't make anti-insulin antibodies," Rewers says. "It is a very important discovery that the very best animal model behaves very similarly to young children who develop diabetes. Now we can use [the mice] to better understand the causes of diabetes in humans and also to test [treatments]."

In an interview to provide objective comment, Jennifer Marks, MD, one of the principal investigators in a large diabetes study, says that earlier tests have established insulin autoantibodies as a marker of childhood diabetes risk. "In young children, it is very predictive of who is going to develop diabetes in the future," Marks, an associate professor at the University of Miami, Fla., tells WebMD.

Manou R. Batstra, PhD, of Erasmus University in the Netherlands, has developed a simple test for the GAA and IA-2 autoantibodies. She says that sometimes, normal children have insulin autoantibodies, and suggests that it would be a bad idea to test only for these antibodies. She tells WebMD that a combination of tests would be more useful.

Eisenbarth and Rewers agree with Batstra that a combination test would be best. However, they say that early detection of anti-insulin antibodies might identify individuals who would most benefit from therapy -- when, and if, such treatments are available.

The large study currently being conducted by Marks and others is still enrolling subjects to test whether small doses of insulin (administered by mouth or injection) can prevent the immune system from attacking insulin-producing cells. U.S. residents interested in more details can call the study's toll-free number, 1-800-HaltDM1. In addition, Eisenbarth says that three private companies now are performing safety trials for various "insulin vaccination" approaches to treating childhood diabetes.

All of the experts interviewed for this article agree that wide-scale screening for childhood diabetes would not be cost effective -- until there is a treatment, at which time the tests might very well become routine.