Dynamics of Islet Autoantibodies During Prospective Follow-Up from Birth up to 15 Years of Age.

CONTEXT We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We assessed also systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. DESIGN HLA-predisposed children (N=1006, 53.0% boys) recruited from the general population in 1994-1997 were observed from birth over a median time of 14.9 (range 1.9-15.5) years for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) autoantibodies, and for T1D. RESULTS By 15.5 years of age, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 (0.3-15.1) years. The ICA seroconversion rate increased towards puberty, but the biochemically defined autoantibodies peaked at a young age. Before the age of 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until the age between 10-15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs. 3.4 years; P=0.01). CONCLUSIONS In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process towards clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.