UF Researchers Screen Newborns For Genetic Susceptibility To Diabetes In Effort To Find Causes And Cures

September 16, 1999

GAINESVILLE—Most cases of insulin-dependent diabetes are discovered only when symptoms appear. But through a sophisticated screening program at the University of Florida, a Gainesville family knows their 20-month-old daughter is all but certain to develop the chronic disorder soon.

As a newborn at Shands at AGH hospital, the girl was tested for genetic susceptibility to the disease. Since then, she has developed immune system markers-but no physical symptoms-indicating her body is destroying its own insulin-producing cells, a process expected to lead to diabetes.

Scientists know that genes are not enough to trigger that destruction, but they do not know which of many suggested culprits, including viruses, diet and other environmental factors, are responsible.

To figure that out, UF researchers have embarked on the PANDA project — the Prospective Assessment in Newborns for Diabetes Autoimmunity.

In the past two years, they have screened more than 4,000 babies, with a plan to test 8,000 more to assess their genetic susceptibility to the disease. Fortified by a $2 million grant awarded by the National Institutes of Health this month, they will use the information to track those considered to be at high risk and try to determine what sets off the disorder.

“Whatever it is, we believe it occurs very early in life,” said Dr. Desmond Schatz, a professor of pediatric endocrinology in UF’s College of Medicine and the study’s co-principal investigator. “If we learn what causes the disease, then we can find a better way to stop it in its tracks or prevent it altogether.”

More than 750,000 Americans have insulin-dependent diabetes, which develops after the body’s infection-fighting white blood cells mistakenly destroy the part of the pancreas that produces insulin. The result is an impaired ability to use and store sugar and other nutrients for energy. Complications include heart disease, stroke, blindness, kidney failure and poor circulation.

Families of infants born at the UF-affiliated Shands HealthCare hospitals, the Orlando-based Florida Hospital chain, North Florida Regional Medical Center in Gainesville, Sacred Heart Children’s Hospital in Pensacola and several other sites are offered the chance to participate in the screening. With parental consent, researchers obtain a drop of blood at the same time blood is obtained for the state-mandated newborn screening program that seeks to detect the congenital disease PKU and other disorders.

UF geneticist Jin-Xiong She, the study’s principal investigator, and his team look for the presence of two specific susceptibility genes, known as HLA-DR and HLA-DQ. While many more genes can contribute to risk, they have not all been identified. With these two genes, scientists can identify 70 to 80 percent of the people who have the potential for developing type 1 diabetes.

“People who have a close relative with type 1 diabetes have a higher risk of getting it than the general population — about a 1-in-20 chance compared to 1 in 300,” said She, who is affiliated with UF’s Genetics Institute and is also an associate professor in the departments of pathology, immunology and laboratory medicine, and pediatrics. “But about 90 percent of the people who have the disease do not have a close relative who also has it.”

Based on the genetic information and family history, researchers assign each infant to a risk status, which ranges from a 1-in-4 probability of developing diabetes, to a 1-in-15,000. Those in the 1-in-15,000 category have a gene that appears to offer protection from the disease.

Researchers will ask families of those at high or moderate risk many questions in the coming months and years to try to pinpoint why some of them will develop diabetes but most won’t.

“We’ll ask how long the infants were breast-fed, when they started on solid food, whether the milk they drank was soy or cow’s milk,” said Dr. Andrew Muir, a clinical assistant professor of pathology and pediatrics. “We’ll also look at when they received their immunizations and the viruses they contracted.”

Such environmental factors appear critical, because even in identical twins, diabetes can strike one and not the other. In follow-up visits, participants also will be tested to see if they have developed specific autoantibodies that indicate an attack on their insulin-producing cells has begun.

“By looking at the genetic information, we’re trying to move the entire study of prevention to a much earlier stage, to try to understand who will develop the autoantibodies,” She said.

The mother of the 20-month-old Gainesville girl said she appreciates knowing ahead of time that diabetes appears likely to be in her daughter’s future.

“We’re trying not to eat sweets as much anymore or sodas. That was really hard, but we figured that if the children are used to eating right, it won’t be so hard when they’re teen-agers,” she said.

The family also hopes their participation in the study will contribute to a cure.

“Hopefully, they’ll eventually be able to do some kind of gene therapy or something so that people won’t get it,” the mother said. “Anything that is helpful, I’m willing to be part of it.”