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OBJECTIVE: To study the interaction among HLA genotype, early probiotic exposure, and timing of complementary foods in relation to risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes. We used a Cox proportional hazards regression model adjusting for potential confounders to study early feeding and the risk of IA in a sample of 7,770 children. RESULTS: Any solid food introduced early (<6 months) was associated with increased risk of IA if the child had the HLA DR3/4 genotype and no probiotic exposure during the 1st year of life. Rice introduced at 4–5.9 months compared with later in the U.S. was associated with an increased risk of IA. CONCLUSIONS: Timing of solid food introduction, including rice, may be associated with IA in children with the HLA DR3/4 genotype not exposed to probiotics. The microbiome composition under these exposure combinations requires further study. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study investigated physical activity and its association with the development of islet autoimmunity and type 1 diabetes in genetically at-risk children aged 5–15 years. RESEARCH DESIGN AND METHODS: As part of the longitudinal Environmental Determinants of Diabetes in the Young (TEDDY) study, annual assessment of activity using accelerometry was conducted from age 5 years. Time-to-event analyses using Cox proportional hazard models were used to assess the association between time spent in moderate to vigorous physical activity per day and the appearance of one or several autoantibodies and progression to type 1 diabetes in three risk groups: 1) 3,869 islet autoantibody (IA)-negative children, of whom 157 became single IA positive; 2) 302 single IA–positive children, of whom 73 became multiple IA positive; and 3) 294 multiple IA–positive children, of whom 148 developed type 1 diabetes. RESULTS: No significant association was found in risk group 1 or risk group 2. A significant association was seen in risk group 3 (hazard ratio 0.920 [95% CI 0.856, 0.988] per 10-min increase; P = 0.021), particularly when glutamate decarboxylase autoantibody was the first autoantibody (hazard ratio 0.883 [95% CI 0.783, 0.996] per 10-min increase; P = 0.043). CONCLUSIONS: More daily minutes spent in moderate to vigorous physical activity was associated with a reduced risk of progression to type 1 diabetes in children aged 5–15 years who had developed multiple IAs. [ABSTRACT FROM AUTHOR]

Objective: Biomarkers predicting risk of type 1 diabetes (stage 3) among children with islet autoantibodies are greatly needed to prevent diabetic ketoacidosis and facilitate prevention therapies.Research Design and Methods: Children in the prospective The Environmental Determinants of Diabetes in the Young (TEDDY) study (n = 707) with confirmed diabetes-associated autoantibodies (GAD antibody, IA-2A, and/or insulin autoantibody) and two or more HbA1c measurements were followed to diabetes or median age 11.1 years. Once confirmed autoantibody positive, HbA1c was measured quarterly. Cox models and receiver operative characteristic curve analyses revealed the prognostic utility for risk of stage 3 on a relative HbA1c increase from the baseline visit or an oral glucose tolerance test (OGTT) 2-h plasma glucose (2-hPG). This HbA1c approach was then validated in the Type 1 Diabetes TrialNet Pathway to Prevention Study (TrialNet) (n = 1,190).Results: A 10% relative HbA1c increase from baseline best marked the increased risk of stage 3 in TEDDY (74% sensitive; 88% specific). Significant predictors of risk for HbA1c change were age and HbA1c at the baseline test, genetic sex, maximum number of autoantibodies, and maximum rate of HbA1c increase by time of change. The multivariable model featuring a HbA1c ≥10% increase and these additional factors revealed increased risk of stage 3 in TEDDY (hazard ratio [HR] 12.74, 95% CI 8.7-18.6, P < 0.0001) and TrialNet (HR 5.09, 95% CI 3.3-7.9, P < 0.0001). Furthermore, the composite model using HbA1c ≥10% increase performed similarly to an OGTT 2-hPG composite model (TEDDY area under the curve [AUC] 0.88 and 0.85, respectively) and to the HbA1c model in TrialNet (AUC 0.82).Conclusions: An increase of ≥10% in HbA1c from baseline is as informative as OGTT 2-hPG in predicting risk of stage 3 in youth with genetic risk and diabetes-associated autoantibodies. [ABSTRACT FROM AUTHOR]