Scientists are casting a wide, tightly woven net with the goal of catching the causes of type 1 diabetes.
In October, study sites worldwide began a four-year process to screen 220,800 healthy babies for genes that put them at risk for type 1 diabetes. They expect to identify the genes in about 13,000 babies, about half of whom will embark with their families on a 15-year journey that may help cure the disease.
“Our hope is to identify environmental factors that determine the risks for type 1 diabetes,” says Dr. Jin-Xiong She, director of the Medical College of Georgia Center for Biotechnology and Genomic Medicine and Georgia Research Alliance Eminent Scholar in Genomic Medicine. “Once you know the risk factors, you can modulate the risk factors to prevent diabetes.”
Five years ago, Dr. She met with other diabetes researchers to discuss such research opportunities. Those conversations led to a request for applications from the National Institutes of Health to investigate environmental triggers of the disease that turn the body’s immune system against the insulin-producing cells of the pancreas.
A few dozen centers applied and the NIH chose six to meet again and devise a comprehensive plan for studying this expansive topic that includes nearly everything in a child’s life, from the water he drinks to when he eats his first cookie.
“Risk factors for type 1 diabetes include two major components: genetic factors and environmental factors. They are about equally important,” says Dr. She. “We have quite a few of the genes identified.” In fact, Dr. She and his colleague, molecular geneticist Cong-Yi Wang, reported in the August 2004 issue of Nature Genetics the discovery of the fourth gene, dubbed SUMO-4. Having these genes increases tenfold the risk of developing type 1 diabetes.
But the environmental factors, which researchers believe are responsible for the increasing incidence of the disease, are still elusive. “There are many suspects, like cow’s milk and the coxsackie viral infection (also known as hand, foot and mouth disease) that have been suggested as triggers for type 1 diabetes. But the literature is very controversial,” says Dr. She.
That’s where TEDDY-- The Environmental Determinants of Diabetes in the Young-- comes in. The study includes newborns in four states and three countries. MCG is the lead site for seven hospitals, including MCG Medical Center, University Hospital and St. Joseph Hospital in Augusta; Northside Hospital in Atlanta; and three hospitals in Gainesville, Fla. Additional lead sites include Barbara Davis Center at the University of Colorado, Pacific Northwest Research Institute in Seattle, the University of Turku in Finland, Lund University in Sweden and the Diabetes Research Institute in Munich, Germany. Moffitt Cancer Center and Research Institute at the University of South Florida is analyzing the data as participants are enrolled over the next four years.
TEDDY is similar to another screening study driven by Dr. She called PANDA--Prospective Assessment in Newborns for Diabetes Autoimmunity--which also uses a drop of blood taken from the umbilical cord or the traditional heel prick to screen newborns for high-risk genes. Older children also are being enrolled in the PANDA study which is following those with the genes for five years.
While
that study continues, the larger study has priority for enrolling newborns, says
Diane Hopkins, research coordinator for the Center for Biotechnology and Genomic
Medicine and multi-site research manager for TEDDY in Georgia and Florida.
“The families make a real commitment to this research,” she says. “We are asking them to record every time the child is sick, every time the child receives medication, whether it’s over-the-counter or prescription. Every time the child goes to a health care provider, even for a well-baby visit, we want to know about it. We are throwing this giant net and reeling in as many answers as we can before we know they are answers.”
“One school of thinking is the triggering of the disease starts in utero, though no one really knows,” says Dr. She. “We need more evidence and we need to know what really triggers the disease.”
They definitely will have plenty of evidence. Project managers will see the study participants every three months for the first four years of life and every six months thereafter to age 15. During that first visit, they will extensively revisit the pregnancy with the mother.
The early years are important because they help shape the immune system, says Dr. She.
As TEDDY follows children through the two age peaks for type 1 diabetes-- 2-4 and 12-15-- researchers will analyze everything from drinking water to nail clippings. Just as water sources differ from one community to another, diabetes triggers may vary geographically. The extensive data will be examined collectively and by individual center to tease out regional differences.
Clearly,
there are regional differences in incidence. Finland and Sweden, for example,
which have largely homogenous populations, have the highest rates of type 1
diabetes in the world, says Dr. She.
No doubt the TEDDY study is a tremendous undertaking for the researchers, as well as the children and parents willing to open up their lives to such scrutiny. But the problem with past studies is they took isolated looks at a very complex disease.
“The bottom line is that it’s not going to be a simple answer,” Mrs. Hopkins says.
- Toni Baker
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An
Eye Toward Prevention