Determinants of islet autoimmunity and clinical implications

• More than 7000 newborns carrying HLA antigen genotypes associated with T1D were enrolled.
• A risk score using autoantibodies, and genetic and clinical markers was found that can aid in predicting the risk of T1D over horizons of up to 8 years.
• Autoimmune phenotypes point to distinct etiologic endotypes.
• Early ‘IAA-first’ phenotype and later a ‘GADA-first’ phenotype may mark distinct triggers of islet autoimmunity.
• Prolonged shedding of enteroviruses predicts development of islet autoimmunity across all TEDDY centers and may be associated with ‘IAA-first’.
• Subtle associations between microbiome taxonomy/function and islet autoimmunity exist, and may also be involved with diet-microbiome interactions.
• Furthermore, gene-micronutrient interactions may influence the risk.

Metabolome signals in the TEDDY study

• Metabolics data profiling was carried out using samples obtained in the TEDDY study.
• Four clusters were identified in the children’s lipidome.
• Autoantibody clusters were also found that showed stratified seroconversion to T1D.
• Erythrocyte omega-3 fatty acids showed a positive interaction with cholesterol esters, but negative correlation with ascorbic acid and 25(OH) vitamin D.
• Ascorbic acid and 25(OH) vitamin D may have a protective effect on T1D progression following seroconversion.

HbA_1c - Is it a good diagnostic predictor of type 1 onset in a pediatric population?

• Risk factors associated with a change in HbA_1c was examined, and identified number of antibodies at HbA_1c change, age at baseline, and HbA_1c at baseline.
• The change in HbA_1c was found to predict T1D in children.
• A rapid change in HbA_1c did not predict T1D.
• Change in HbA_1c was a good diagnostic measure in the young population, and was as reliable as a single oral glucose tolerance test for T1D.

Dissecting the type 1 diabetes and celiac disease overlap in the TEDDY study

• Extensive overlap was found between celiac autoimmunity (TGA, transglutaminase autoantibodies) and T1D in the TEDDY cohort.
• Islet autoimmunity usually preceded TGA, and islet autoimmunity increased the risk of subsequent TGA.
• While gluten intake was a strong risk factor for TGA, neither intake nor age at gluten introduction were consistent risk factors for both types of autoimmunity.
• Enteroviral infection was associated with both islet autoimmunity and TGA, the latter when stratified by gluten intake, and may explain some of the overlap.