Diabetes-Associated Autoantibodies and Progression to Clinical Type 1 Diabetes

Type 1 diabetes is a chronic disease caused by immune-mediated destruction of the pancreatic beta-cells. The asymptomatic prediabetic period before onset of the clinical disease and the causes leading to the autoimmune reaction remain poorly characterized.

The objective here is to study the autoimmune process, especially appearance of diabetes-associated autoantibodies, known to be strongly predictive markers of clinical T1D. The measured diabetes-associated autoantibodies include ICA (islet cell antibodies), GADA (antibodies to 65 kilodalton isoform of glutamic acid decarboxylase), IAA (insulin autoantibodies) and IA-2A (antibodies to protein tyrosine phosphatase related IA-2 protein). Autoantibodies are measured in the DIPP and TEDDY studies from blood samples at 3- to 6- month intervals in Turku and 3- to 12- month intervals in Tampere and Oulu. Autoantibody positivity, especially if two or more of the measured autoantibodies are found, increases substantially disease risk. However, children may be autoantibody positive for several years before progressing to clinical diabetes, and some seem to remain healthy at least until adulthood. We aim to find out in which age autoantibodies typically appear, why this happens, for how long time children are autoantibody positive before progressing to diabetes, what is the predictive value of the autoantibody levels. We also study whether it is possible that diabetes-associated autoantibodies disappear spontaneously from some children. In the future, we hope to be able to more accurately predict the risk of diabetes in individual childen and understand the factors which trigger the autoimmune process.