Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes

OBJECTIVE - To study the characteristics of type 1 diabetes in very young children. RESEARCH DESIGN AND METHODS - Clinical outcome, islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies against GAD (GADA), IA-2 antibodies (IA-2A), and HLA-DQBI-defined genetic risk were analyzed in 35 children diagnosed with type 1 diabetes before 2 years of age and compared with those in 146 children who were diagnosed between 2.0 and 4.9 years of age and with those in 620 children diagnosed between 5.0 and 14.9 years of age. RESULTS - The youngest age-group had severer metabolic decompensation at clinical onset, and their serum C-peptide levels, compared with those of older children, were lower at the time of diagnosis and during the first 2 years after the diagnosis. The levels of ICA and IAA were highest in children <2 years of age, but there were no differences in GADA levels among the three age-groups. The youngest age-group had the lowest IA-ZA levels. The HLA DQBI*02/*0302 genotype associated with strong genetic susceptibility was more frequent in children diagnosed <5 years of age, whereas the proportion of children carrying a genotype, which includes protective alleles, was higher among those diagnosed at greater than or equal to 5 years of age. CONCLUSIONS - The clinical presentation of type 1 diabetes at a very young age is associated with severe metabolic decompensation, poorly preserved residual beta-cell function, strong humoral autoimmunity against islet cells and insulin, and strong HM-defined disease susceptibility.