Jeffrey Krischer, PhD
Early findings from the Environmental Determinants of Diabetes in the Young (TEDDY) study, the largest and most comprehensive study of events leading up to diabetes in children, have already changed our understanding of type 1 diabetes in youth. The next analysis of genetic and environmental factors affecting the etiology and pathogenesis of type 1 diabetes will likely shift clinical paradigms once again.
“We are just beginning to evaluate a wide range of potential environmental and genetic factors in autoimmunity leading to type 1 diabetes,” said Jeffrey Krischer, PhD, a TEDDY study coordinator and Professor of Pediatrics and Internal Medicine at the University of South Florida’s College of Medicine. “We will present new findings in Orlando that will change the conversation about type 1 diabetes in youth.”
Dr. Krischer will be the first presenter at a Scientific Sessions symposium on Saturday, June 23, titled Lessons Learned from the Environmental Determinants of Diabetes in the Young (TEDDY) Study—Insights into Early Autoimmune Type 1 Diabetes. The session is supported by a grant from the Leona M. and Harry B. Helmsley Charitable Trust.
TEDDY is following 8,676 children in four countries from birth to 15 years of age who are at elevated risk for type 1 diabetes. The current median age of the study population is nine years and data collection is ongoing.
The study’s goal is to evaluate the contributions of genetics, environment, and gene-environment interactions on the development of the first disease markers through the progression to clinical diagnosis of type 1 diabetes.
The study is amassing a vast collection of data and biosamples to track and assess changes in the microbiome, proteome, diet, toxicants, and infectious agents that could be related to autoimmunity against beta cells and type 1 diabetes, Dr. Krischer explained.
Biosamples are used to trace the appearance and impact of bacterial and viral infections, as well as the immune system response to these exposures. Potential toxicants of interest include trace elements and heavy metals.
Study participants are providing DNA samples along with regular serum, plasma, urine, stool, and cortisol samples during the first 15 years of life. Samples are analyzed using whole genome sequencing, whole exome genotyping, single nucleotide polymorphisms, RNA sequencing, RNA microarrays, and other technologies as they develop and mature.
“We designed TEDDY with the best available knowledge and technology of the time, but we didn’t commit to any specific technology until we had samples in hand and were ready to test,” Dr. Krischer said. “We are collecting samples over the years and deciding later when the most appropriate time for testing might be. We are constantly evaluating technologies and whether they are ready for our kinds of analysis.”
The decision to take advantage of technology and knowledge advances gives researchers considerable flexibility, Dr. Krischer said. Teams looking into genetics, immune markers, infectious diseases, clinical factors, and other areas are able to use the latest study techniques and take advantage of falling prices and increasing sophistication in sequencing technologies.
“We are just now doing whole genome sequencing,” Dr. Krischer said. “Now that we are nine years into the study, the cost has come down incredibly, which finally makes it financially feasible to sequence whole genomes on selected cases and their controls.”
The study population comes from three U.S. clinical centers in Seattle, Denver, and a combined group from the Augusta-Atlanta areas in Georgia and Gainesville, Florida, plus centers in Sweden, Finland, and Germany. All sites have contributed to the enrollment of the study population, which includes first-degree relatives of family members diagnosed with type 1 diabetes and high-risk individuals from the general population.
“We have already shown that that type 1 diabetes, at least in small children, is composed of at least two endotypes—two separate disease processes with distinct risk factors,” Dr. Krischer said. “We are now talking about type 1 diabetes as being a heterogeneous collection of diseases, not a single disease, and have the data to support this concept. We are investigating different etiological factors related to pathogenesis and also how autoimmunity progresses to diabetes. This is brand new information and vitally important for everyone who is dealing with children who show signs of autoimmunity and the initiation of processes leading to clinical diabetes.”
