Thousands of blood, saliva, urine, mucus and stool samples contributed by “TEDDY” kids from around the world are finally starting to bear fruit.
The 8,676 children from the United States, Finland, Sweden and Germany, now ages eight to 13, began contributing to “The Environmental Determinants of Diabetes in the Young” study when they were just three months to a year old. The study is searching for the causes of type 1 diabetes, and researchers hope to discover how genetic and environmental factors—like childhood infections, or diet—collude to cause the disease.
The study follows children through age 15, and is unique in its long-term, frequent monitoring of at-risk children from an early age. Researchers began collecting samples over a decade ago, but analyses have escalated only recently as technologies such as genome sequencing have become more widely available and more affordable.
The ultimate goal: to understand why and how type 1 diabetes develops in some genetically susceptible children, but not in others, and to develop new strategies to prevent, delay or even reverse the disease.
“We have already shown that type 1 diabetes, at least in small children, is composed of at least two endotypes—two separate disease processes with distinct risk factors,” Jeffrey Krischer, PhD, said in a American Diabetes Association article.
Krischer, a TEDDY study coordinator and Professor of Pediatrics and Internal Medicine at the University of South Florida’s College of Medicine, presented this past weekend in Orlando at an ADA Scientific Sessions symposium.
Most recently, TEDDY has found clear differences in how autoimmunity—when the body attacks itself—is triggered based on genetic factors and environmental exposures. In type 1 diabetes, the body’s infection fighting cells, called immune cells, attack the pancreas.
TEDDY has found that genetics and environmental factors determine which autoantibodies a child develops first, IAA—an antibody that directly attacks insulin—or GADA, one that destroys the enzyme glutamate decarboxylase, which regulates the insulin-producing beta cells in the pancreas. Autoantibodies are immune proteins that mistakenly target and seek to destroy a person’s own tissues or organs.
Around 90 percent of those with type 1 diabetes develop one autoantibody first. Many end up with both autoantibodies days or even years later, Dr. Jin-Xiong She, principal investigator of TEDDY’s Georgia/Florida site, told Science Daily. She is also director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Augusta University.
A study utilizing TEDDY data in the September 2017 issue of the Diabetes Care Journal looked at the progression of infants with high-risk genotypes for type 1 diabetes to age six. Results showed IAA occurred earlier in the children than GADA, and then declined, while GADA rose and remained constant. Furthermore, researchers were able to identify genes that demonstrated increased risk to both autoantibodies, another gene that was protective of IAA, as well as one that demonstrated an increased risk of GADA.
For environmental risks, the study found that factors including being male, having a father or sibling with diabetes, getting probiotics under 28 days of age, and increased weight at age 12 months were associated with IAA only. Having a father with diabetes and weight at 12 months were associated with GADA only. Having a mother with diabetes, however, was not a significant risk factor.
In an analysis of 7,479 TEDDY children as of January 2016, Riitta Veijola, MD, PhD, professor of pediatrics at University of Oulu, Finland, also found that TEDDY children with a second-degree relative with type 2 diabetes showed a much slower progression from the development of autoantibodies against the pancreas to clinical type 1 diabetes versus children without such relatives.
This was a finding consistently observed in TEDDY children across Finland, Germany, Sweden and the United States, Veijola said in an Endocrinetoday article. “We believe this is a true phenomenon that needs to be studied further,” Veijola said.
The finding, she added, suggests type 2 diabetes-susceptibility genes might affect the progression of type 1 diabetes, and that families who have second-degree relatives with type 2 diabetes might be able to modify their lifestyle to stave off type 1 diabetes.
Research is ongoing, and TEDDY coordinators hope to uncover an abundance of data that will help shape how physicians treat, and work to prevent, the disease.
“Unfortunately, at this stage, the ability to predict which individuals will actually develop autoimmunity or diabetes is still very limited in TEDDY,” Krischer said in the Endocrinetoday article. “We still have to work harder. But, TEDDY has a wealth of new data — metabolomics, genomics, proteomics and microbiome data are coming online that may improve prediction.”