A Secular Increase in the Incidence of Islet Autoimmunity Among Colorado Children With Moderate-Risk HLA Genotypes
Kirk R. Hohsfield, Fran Dong, Kathleen Waugh, Andrea K. Steck, Teresa Buckner, Randi K. Johnson, Patrick M. Carry, Brigitte Frohnert, Marian Rewers, Jill M. NorrisOBJECTIVE
We investigated islet autoimmunity (IA) incidence trends among Colorado children born 1993–2010 in Diabetes Autoimmunity Study in the Young (DAISY) and The Environmental Determinants of Diabetes in the Young (TEDDY) and whether HLA genotype or early-life environmental exposures contributed to observed increases.
RESEARCH DESIGN AND METHODS
We analyzed the risk of IA among 2,734 Colorado children representing three birth cohorts (BCs): BC1 (1993–1998), BC2 (1999-August 2004), and BC3 (September 2004–2010). Cox models evaluated IA by BC, with time-varying coefficients, BC-HLA interaction, and stratification by type 1 diabetes family history. Mediation analyses examined age at gluten introduction, weight-for-age Z-score, and maternal smoking.
RESULTS
IA increased across BC1–BC3 (7.0%, 10.7%, and 12.7%). At age 1, moderate-risk HLA participants in BC2 and BC3 had, respectively, 2.57 and 6.19 times the IA risk of BC1. By age 5, effects attenuated. No selected environmental exposures mediated the increased incidence.
CONCLUSIONS
IA increased among Colorado children born 1993–2010, with the strongest effects among moderate-risk HLA genotypes in later BCs.