Correspondence

Genetics of Type 1A Diabetes

N Engl J Med 2009; 361:211July 9, 2009

Article

To the Editor:

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 follow-up 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

Vincenzo Sepe, M.D.
Policlinico San Matteo, 27100 Pavia, Italy
v.sepe@smatteo.pv.it

Andrea Loviselli, M.D.
University of Cagliari, 09124 Cagliari, Italy

Gian Franco Bottazzo, M.D.
Bambino Gesù Scientific Institute, 00165 Rome, Italy

4 References

1. 1

   Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009;360:1646-1654
   Full Text | Web of Science | Medline

2. 2

   Aly TA, Ide A, Jahromi MM, et al. Extreme genetic risk for type 1A diabetes. Proc Natl Acad Sci U S A 2006;103:14074-14079
   CrossRef | Web of Science | Medline

3. 3

   Sepe V, Eldridge S, Loviselli A, Cirillo R, Bottazzo GF. Definition of cut-off points for autoantibody assays in cohorts of healthy individuals. Lancet 1996;347:693-693
   CrossRef | Web of Science | Medline

4. 4

   LaGasse JM, Brantley MS, Leech NJ, et al. Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: an 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care 2002;25:505-511
   CrossRef | Web of Science | Medline