It may also reflect related UVR and vitamin D metabolism genes. We have previously shown that the association between vitamin D receptor gene and T1D onset varies by regional UVR levels [33]. The accelerator hypothesis postulates that the more obese child should develop T1DM at a younger age and that higher insulin levels linked to insulin resistance may underlie the formation of insulin AA [34]. Further, β cell upregulation in response to obesity-linked insulin

resistance may lead to upregulated cellular enzymes and associated antibodies such as GADA [34]. However, here, children under 5 were not heavier than older T1DM children. Also, no link between obesity and autoantibody levels at T1DM diagnosis were observed. One prospective cohort study has demonstrated that mothers who do not take vitamin D supplementation in pregnancy or have lower vitamin D stores in pregnancy Nintedanib have offspring who are more likely to develop AA by age 3 years [35]. However, no associations were observed in the Finnish Diabetes Prediction and Prevention Ipatasertib molecular weight study [36]. In Australia, vitamin D stores are predominantly derived from radiation exposure to the skin. Here, lower sun exposure in the winter prior to presentation

was associated with elevated GAD antibodies at onset. Intriguingly, the association between low early life sun exposure and elevated GADA antibodies was more Cell press evident among children present with T1DM onset at age <5 years, indicating that low early life UVR exposure or low vitamin D stores may play a particular role in the generation of GAD antibodies among children who develop T1DM by age 5 compared to those who present with T1DM at older ages. However, as this is the first report of such an association,

replication of these findings are required. The finding of effect modification by age of onset, together with the findings in the Swedish cohort that maternal vitamin D supplements were associated with GADA at 1 year but not at 2.5 years [35] indicate that further analysis of the Finnish cohort [36] is warranted to examine whether the null findings overall mask a difference in the effect of maternal vitamin D status by age of advanced autoimmunity or T1DM onset. Strengths of this study includes that it is on a well defined population within a specific geographical area. Further this study examined not only phenotype factors but also environmental factors taking into account potential confounding effects of age, sex and family history of diabetes. Limitations of this study include that it is based on cases only, limiting causal inference and data on HLA type, a well- known associate of autoantibody levels, was not available. However, collection of control data is shortly due for completion.