Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study

Type 1 diabetes, which is the most common metabolic disease in children and
adolescents, begins with a pre-clinical phase which is defined by the
presence of islet autoantibodies. This pre-clinical phase is variable in
duration with onset of clinical diabetes occurring months to decades after
the appearance of islet autoantibodies. In this study, we found that a
genetic risk score that had previously been shown to predict islet
autoimmunity also predicts disease progression. The risk score may therefore
be used to identify subgroups with fast or slow progression in clinical
studies. (By Dr. Andreas Beyerlein, )

Cumulative risks of (A) development of multiple islet autoantibodies after first appearance of any autoantibodies, (B) development of type 1 diabetes after first appearance of any autoantibodies and (C) development of type 1 diabetes after first appearance of multiple autoantibodies, in children with the HLA DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype. P values were calculated using log-rank tests. The groups were defined by quartiles of the genetic risk score (green: lower quartile; blue: two medium quartiles; orange: upper quartile). HLA, human leucocyte antigen.

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