Diabetic autoimmunity in infants and pre‐schoolers with type 1 diabetes

The incidence of type 1 diabetes is increasing most rapidly in children under 5 yrs of age, a group where the disease appears to be more accelerated than traditional type 1 diabetes. Little is known about demographics, and markers of diabetes autoimmunity, in infants and pre-schoolers with type 1 diabetes. We report an analysis of 47 children diagnosed with type 1 diabetes prior to 5 yrs of age compared with a representative cohort (n=49) diagnosed after 5 yrs of age, and all were followed at Loma Linda University (LLU) Children's Hospital. Ethnic, familial, seasonal, and autoimmune marker characteristics are outlined. To determine the prevalence of diabetes autoimmune markers, ICA512, GAD65 and insulin autoantibodies (IAA) antibodies were measured. Children with early-onset diabetes had a significantly higher incidence of viral illness symptoms (p=0.005) and diabetic ketoacidosis (DKA; p=0.017) at the time of diagnosis. However, hemoglobin A1C (HbA1c) levels at diagnosis were significantly higher in the later-onset group (p=0.001). A honeymoon period was reported in 14.8% of children diagnosed before 5 yrs of age compared with 42.1% in those diagnosed over 5 yrs of age (p=0.038). Islet-cell antibodies (ICAs) and glutamic acid decarboxylase (GAD) antibody titers were significantly different between early- and later-onset groups. ICA titers were positive in 35.29%, and GAD in 41.38% of the early-onset group versus 70.83 and 71.74% in children with later-onset disease, (p=0.001 and 0.009, respectively). IAA titers, drawn after instituting insulin therapy, were not significantly different between the two groups. GAD and ICA512 antibody results suggest a relative lack of diabetes immune markers in infants and toddlers with new-onset diabetes. This finding, and the apparent shorter pre-clinical phase reflected in the lower HbA1c values, may indicate age-related differences in type 1 diabetes autoimmunity or the existence of non-autoimmune diabetogenic mechanisms in younger children.