Investigators from The Environmental Determinants of Diabetes in the Young (TEDDY) study presented the latest results from the ongoing study during the Scientific Sessions.
The presentation can be viewed by registered meeting attendees at ADA2020.org through September 10, 2020. If you haven’t registered for the Virtual 80th Scientific Sessions, register today to access all of the valuable meeting content.
TEDDY Co-Chair Marian Rewers, MD, PhD, began by reviewing the background of the study and summarizing its key findings to date.
“One of the initial interesting observations from TEDDY is that islet autoimmunity develops quite early,” said Dr. Rewers, Professor of Pediatrics at the Barbara Davis Center at the University of Colorado School of Medicine. “In many kids, it can be detected in the first three years of life.”
Dr. Rewers said data on insulin autoantibodies (IAA) and glutamic acid decarboxylase autoantibodies (GADA) suggest that there may be two distinct type 1 diabetes endotypes that differ by genetic background and environmental risk factors—an earlier onset “IAA-first” phenotype followed by a later onset “GADA-first” phenotype.
Dr. Rewers reviewed research into genetic and clinical markers that indicates that screening for islet autoimmunity in high-risk youth should start in the first two years of life. He also reviewed data on potential environmental triggers of islet autoimmunity, including viral infections and the gut microbiome.
“TEDDY found respiratory infections within any nine-month period predicted islet autoimmunity in the following three months,” Dr. Rewers said. “Specifically, we found evidence of an association between enterovirus and predictable appearance of islet autoimmunity.”
Subtle associations between microbial taxonomy and development of islet autoimmunity have also been observed in the TEDDY cohort. Dr. Rewers said data show probiotic use in the first few weeks of life may be protective against islet autoimmunity, while antibiotic use in early life was not shown to increase risk of autoimmunity for type 1 diabetes or celiac disease.
Finally, Dr. Rewers reviewed findings about micronutrients and islet autoimmunity.
“We found that high levels of vitamin D and the vitamin D receptor genotype were associated with lower risk of islet autoimmunity. Higher vitamin C levels were also associated with lower risk,” he said. “Free fatty acids in the erythrocyte wall were associated with a protective effect as well. However, I think it’s a little bit too early to recommend infants or young children take more vitamin D or C, or fatty acid supplements. We need randomized controlled trials to show there is efficacy before it becomes a widespread recommendation.”
Following Dr. Rewers’ presentation, three other TEDDY investigators offered further insight from the study.
Biostatistician Qian Li, PhD, Assistant Professor in the Health Informatics Institute at the University of South Florida, provided an in-depth review of metabolome signals in TEDDY.
She said the study aims to identify metabolic biomarkers for islet autoimmunity and determine if there are distinct metabolic biomarkers for GADA-first and IAA-first endotypes. To achieve this, longitudinal lipidome profiles of GADA-first and IAA-first participants were classified into clusters. Associations were found indicating that circulating ascorbic acid and vitamin D may have a protective effect in type 1 diabetes, but Dr. Li said further analysis is needed to confirm this finding.
Kendra Vehik, PhD, MPH, an epidemiologist and Assistant Professor in the Health Informatics Institute at the University of South Florida, reviewed data from TEDDY and other studies looking at the efficacy of A1C as a diagnostic prognosticator of type 1 diabetes onset in patients younger than 21 years of age.
“The take home message from this analysis is that an A1C threshold of greater than 6.5% alone is not a good indicator or diagnostic in a pediatric population,” she said. “However, using a relative measure over two or more serial measures was found to be a good predicator of type 1 diabetes in a pediatric population.”
TEDDY data show that children with a 10% to 20% relative change, or .5% absolute change in A1C from baseline had an increased risk of progression to type 1 diabetes.
“Percent change in A1C is a useful, noninvasive measure to predict likelihood of further progression to type 1,” Dr. Vehik said. “A relative change of 10% or greater from baseline significantly increased the risk of progression to type 1 diabetes in TEDDY children, independent of other known risk factors.”
William Hagopian, MD, PhD, Clinical Associate Professor at Pacific Northwest Research Institute at the University of Washington, shared data from TEDDY that indicate how type 1 diabetes and celiac disease overlap.
“In TEDDY, we have a signal for enterovirus in celiac and a signal for enterovirus in type 1 diabetes,” he said. “The observed overlap between islet autoimmunity and celiac autoimmunity in TEDDY was greater than expected. Islet autoimmunity usually preceded celiac autoimmunity. In addition, islet autoimmunity increased the risk of subsequent celiac autoimmunity.”
Further studies analyzing the stool virome of celiac patients in the TEDDY cohort are underway to explore the effect of gluten intake on autoimmunity.