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Expert commentary

by Prof. Tatjana Milenkovic, MD

The updates from the Teddy Study are very interesting and intriguing for every curious clinician or scientist. The Environmental Determinants of Diabetes in the Young – or in short TEDDY – was looking for the causes of type 1, diabetes, because not only the incidence of type 2, but also the incidence of type 1 diabetes is constantly increasing, and it surprisingly doubles every 20 years. The TEDDY Study was designed to follow children with and without a family history of type 1 diabetes, in order to understand which environmental factors contribute to the disease. More than 400,000 newborns were screened, of which about 8000 were successfully recruited in the study and followed very closely from birth to the age of 15.

Participants provided information about diet, illnesses, psychosocial risk factors, and more. Then, they were followed and tested for the presence of autoantibodies - insulin autoantibodies (IAA) and glutamic acid decarboxylase autoantibodies (GADA). Very interestingly, the study has shown that these two autoantibodies represent separate disease processes with distinct risk factors that both result in type 1 diabetes.

Clinical implications of this finding show that the screening for islet autoimmunity should start in the second year of life. A risk score using autoantibodies and genetic markers enables individualized type 1 diabetes prediction up to 8 years. Optimal primary prevention may differ for children at risk with the early ‘IAA-first’ phenotype versus the late ‘GADA-first’ phenotype because of distinct triggers of islet autoimmunity. Some gene-micronutrient interactions may influence this risk, such as vitamin D, vitamin C, and n-3 polyunsaturated fatty acids in the erythrocyte wall, but randomized trials are needed to confirm this observation.

Regarding metabolome signals in TEDDY, four clusters were identified in the children’s lipidome. It was also shown that the ascorbic acid and 25(OH) vitamin D may have a protective effect on progression of type 1 diabetes, following seroconversion.

This study further demonstrated that HbA1c is a good diagnostic predictor of onset of type 1 diabetes in a pediatric population. Higher HbA1c in high-risk non-diabetic individuals with islet autoantibodies will increase the risk of progression to type 1 diabetes in both asymptomatic and symptomatic children. Percent change in HbA1c, but not a rapid change, can be a useful non-invasive measure to predict further progression to type 1 diabetes in children.

Finally, the overlap of type 1 diabetes and Celiac disease in TEDDY was greater than expected. Insulin antibodies IA usually preceded tissue transglutaminase antibody (TGA). Although gluten intake amount was a strong risk factor for TGA, neither intake nor age at gluten introduction were risk factors for either type of autoimmunity. It was shown that entero-viral infection was associated with both IA and TGA.

So far, TEDDY has not pinpointed the conclusive causes of type 1 diabetes, but it has revealed new associations that warrant further exploration.

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