Browsing by Subject "GAD antibodies"

Aims/hypothesis To characterise rapid progressors to type 1 diabetes among children recruited from the general population based on HLA-conferred disease susceptibility. Methods We observed 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study from birth for development of beta cell autoimmunity and type 1 diabetes over a median follow-up time of 16.2 (range 0.9-21.1) years. Islet cell antibodies, and autoantibodies to insulin (IAA), GAD (GADA), and islet antigen 2 (IA-2A) were analysed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years after autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers including 25 non-HLA single nucleotide polymorphisms (SNPs) predisposing to type 1 diabetes. Results Altogether 1645 children (22%) tested positive for at least one diabetes-associated autoantibody, and 248 (15%) of the seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n=42, 17%), and 5.4 years in slower progressors. Rapid progression was observed both among young and early pubertal children. Compared to slower progressors, rapid progressors had higher frequency of multipositivity, higher titres of ICA, IAA, and IA-2A at seroconversion, and higher prevalence of the secretor genotype in the FUT2 gene. Compared to autoantibody-positive non-progressors, rapid progressors were younger, carried more often the high-risk HLA genotype, the FUT2 secretor genotype, and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA, IA-2A, and multipositivity, and higher titres of all four autoantibodies at seroconversion. Conclusions At seroconversion, individuals with rapid progression to type 1 diabetes are characterised by young age, higher autoantibody titres, positivity for multiple autoantibodies, and higher prevalence of a FUT2 SNP. The double-peak profile of seroconversion age among the rapid progressors demonstrates for the first time that rapid progression may take place not only in young children, but also in children in early puberty. Rapid progressors might benefit from careful clinical follow-up and early preventive measures.