Associations of growth patterns and islet autoimmunity in children with increased risk for type 1 diabetes: a functional analysis approach

Background: Several studies indicate associations between early growth and type 1 diabetes (T1D). However, it remains an open question whether these findings can be translated to typical growth patterns associated with increased risk for T1D-associated islet autoimmunity. Methods: We analyzed pooled data from 2236 children followed up in two large prospective German birth cohorts with a genetically increased risk for T1D including 18 564 measurements of height and weight, which were transformed to sex-and age-specific standard deviation scores (SDS). A total of 191 children developed any islet autoantibodies, 101 multiple islet autoantibodies. We applied a model-based clustering technique to derive typical height and body mass index (BMI) growth patterns, stratified for maternal T1D status. These patterns were used to predict islet autoimmunity in logistic regression models, adjusted for potential confounders. Results: Growth patterns were not associated with islet autoimmunity in the whole dataset and in children of diabetic mothers, respectively. In children of non-diabetic mothers, however, islet autoimmunity was associated with rapidly increasing BMI SDS values until the age of 3 yr [adjusted odds ratio (95% confidence interval): 2.02 (1.03, 3.73) for development of any islet autoantibodies) and with consistently above average height SDS values [odds ratio: 2.21 (1.15, 4.17)]. In contrast, a pattern of high height SDS values at birth followed by a decrease to average values after 3 yr was associated with a reduced rate of islet autoimmunity [odds ratio: 0.16 (0.01, 0.62)]. Conclusion: Early growth patterns may be associated with T1D-related islet autoimmunity risk in children of non-diabetic mothers.