Type 1 Diabetes Triggered First Two Years of Life, Research Says

New data from the Environmental Determinants of Diabetes in the Young (TEDDY) study illuminate the environmental triggers that are thought to cause the autoimmune response leading to type 1 diabetes(T1D) and celiac disease. The data was presented in a symposium at the American Diabetes Association meeting.

TEDDY is an international multi-center trial researching the potential causes T1D in children. The study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).It has been collecting prospective data since 2004, researching the link between genetic and environmental factors in the autoimmune destruction of the beta islet cells of the pancreas.

Although many children are genetically predisposed to T1D, not all children develop it, resulting in the conclusion that an environmental trigger is required. The study enrolls infants identified as “at-risk” for developing T1D and follows them for 15 years to look for the appearance of various beta-cell autoantibodies and diabetes. TEDDY has also studied biomarkers that can predict faster or slower progression to diabetes after the autoimmune destruction has begun.

An update of the results presented at the ADA meeting this week showed that the destruction of beta islet cells begins in the first two years of life, and that there are two clearly different genetic subtypes of T1D.

“There appear to be two subtypes of T1D that differ by genetic factors and immune phenotypes,” said study TEDDY co-chair Marian Rewers, MD, PhD, a professor of pediatrics and medicine and executive director of the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine. “Metabolomic biomarkers may offer clues to the subtypes and whether a child develops T1D. Interestingly, HbA1c has very different predictive characteristics for progression to clinical diabetes in children with islet autoantibodies, compared to adults with risk factors for type 1 diabetes.”

Research also showed that the persistent presence of enterovirus B species in a child’s stool predicts development of islet autoimmunity, especially the earlier subtype characterized by the presence of autoantibodies to insulin.

Researchers say there are also subtle differences in the composition and function of gut microbiome in children who develop islet autoantibodies, compared to controls, and data show that the early use of probiotics may decrease the risk, while use of antibiotics was not related to islet or celiac autoimmunity.

The study has also found potentially beneficial effects of vitamin D, vitamin C, or a diet rich in polyunsaturated fatty acids, though these observations need to be confirmed in randomized clinical trials.

Celiac disease shares many genetic factors with T1D, noted Dr. Rewers. For this reason, TEDDY investigators follow study participants for both T1D and celiac disease in an attempt to determine why some children with high-risk genes develop T1D or celiac disease, while most remain disease-free. Recently reported TEDDY research showed an association between gluten consumption in the early years of childhood and an increased risk of celiac disease among genetically predisposed children.

“While T1D and celiac disease share a lot of genetic characteristics, there are intriguing differences in the ways these diseases develop and progress,” added Dr. Rewers. “TEDDY is contributing exciting clues for design of future trials to prevent both T1D and celiac disease.”

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Andrén Aronsson C, Lee HS, Hård Af Segerstad EM, et al. Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk. JAMA. 2019;322(6):514-523. doi:10.1001/jama.2019.10329