Early Appearance of Diabetes-Associated Autoantibodies in Prepubertal Children Progressing to Clinical Type 1 Diabetes.

The ongoing type I Diabetes Prediction and Prevention project (DIPP) aims at studying processes leading to type 1 diabetes (TID). The study starts with screening of newborn babies for HLA class II conferred risk for T1D. Those at risk are recruited to frequent follow-up, and autoantibodies against β-cell antigens (ICA, IAA, GADA, IA-2A) are measured at 3-month intervals until two years of age, and then half-yearly. Children who develop signs of β-cell autoimmunity are invited to a separate prevention trial comparing efficacy of daily nasal insulin administration to that of placebo. In Turku, 54 DIPP children followed since birth have progressed to T1D. They all had diabetes-related autoantibodies in at least one sample before reaching the diagnosis of T1D. 73% of the children had developed at least one autoantibody before the age of 2 years, and 88% before the age of 3 years. The first autoantibody was most often IAA either alone (22 children; 41%) or together with other antibodies (18 children; 33%). In 26% of children another type of antibody was the first to appear. Before development of T1D 93% of the children were positive for ICA, 94% for IAA, 76% for IA-2A and 80% for GADA. Time from seroconversion to multiple autoantibody positivity was only 0.4±0.8 years (mean±SD). Time from seroconversion to diabetes varied from 0.1 to 7.3 years (mean 2.8). The age at diabetes diagnosis varied from 0.8 to 10.3 years (mean 4.5). 33 children (61%) participated in the prevention trial. To conclude, our sample series reaching from birth to clinical T1D show that almost all children progressing to T1D are multiple autoantibody positive before the disease develops. In almost all cases seroconversion happens at an early age, years before the clinical disease, underlining the importance of life events during the first two to three years of life on development of T1D. [ABSTRACT FROM AUTHOR]