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2. TEDDY reveals gene-environment-gene interactions, diet influences progression of T1D

      The Environmental Determinants of Diabetes in the Young (TEDDY) is an international trial designed to identify the environmental factors and gene-environment interactions which causes islet autoimmunity and type 1 diabetes. The analyses show that several environmental factors such as respiratory infections, enteroviruses, and even a diet high in vitamins D or C can probe the progression of the disease. As per the study, islet autoimmunity develops “quite early” for many children who go on to develop the disease and for many, within the first 2 years of life and metabolomic biomarkers may offer clues to the subtypes and whether a child develops type 1 diabetes.

      The analysis of the environmental factors which trigger the progression of the disease in a nested case-control study of TEDDY participants when aged 3 to 48 months, revealed that the microbiota, particularly enterovirus B, predict the appearance of islet autoimmunity. The association was stronger among children with the IAA-first phenotype compared with children with the GADA-first phenotype according to Rewers, a TEDDY researcher. The research also put forth the observation of children who are positive for IAA autoantibodies first, or “IAA-first” children, are prone to have a different disease course compared with “GADA-first” children who develop GADA autoantibodies first. The findings support the emerging concept of the heterogeneity of type 1 diabetes. TEDDY also observed the potentially beneficial effects of vitamin D, vitamin C or a diet rich in polyunsaturated fatty acids, although these observations must be confirmed in randomized clinical trials. But high levels of vitamin D were found to be protective among TEDDY children with the vitamin D receptor (VDR) genotype, whereas higher vitamin C levels were associated with a lower risk for islet autoimmunity, although there was no gene/vitamin D interaction was noticed.

      The researchers also obtained an interesting fact regarding HbA1c that it 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. The findings were presented at the American Diabetes Association’s 80th Scientific sessions.

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