Genetics of Type 1A Diabetes

In their review article on the genetics of type 1A diabetes, Concannon et al. (April 16 issue),1 citing Aly et al.,2 state that the disorder develops in approximately 1 of 20 persons with high-risk HLA haplotypes. Such data refer to siblings of persons with type 1A diabetes. The real challenge is to identify the development of type 1A diabetes in the general population. A study involving 1031 healthy Sardinian schoolchildren (age range, 10 to 16 years)3 showed that after a followup period of 2.7 to 8.2 years, type 1A diabetes developed in 1 of 8 children who were positive for islet-related autoantibodies. Another study, involving 3000 schoolchildren,4 showed that type 1A diabetes developed within 10 years in children with two or more autoantibodies to distinct islet antigens, with a positive predictive value of 50%. We believe that only persons with islet autoantibodies would benefit from genotyping when “true risk variants for type 1 diabetes are fine mapped, identified, and characterized.”1