Interaction between dietary iron intake and genetically determined iron overload: risk of islet autoimmunity and progression to type 1 diabetes in the TEDDY study

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posted on 2023-03-03, 16:38 authored by Steffen U. Thorsen, Xiang Liu, Yachana Kataria, Thomas Mandrup-Poulsen, Simranjeet Kaur, Ulla Uusitalo, Suvi M. Virtanen, Jill M. Norris, Marian Rewers, William Hagopian, Jimin Yang, Jin-Xiong She, Beena Akolkar, Stephen Rich, Carin Andrén Aronsson, Åke Lernmark, Anette-Gabriele Ziegler, Jorma Toppari, Jeffrey Krischer, Hemang M. Parikh, Christina Ellervik, Jannet Svensson, the TEDDY Study Group

Objective

To examine if iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).

Research Design and Methods

In “The Environmental Determinants of Diabetes in the Young” (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.

Results

We found a U-shaped association between iron intake and risk of GADA as first autoantibody. In subjects with GRS>=2 iron risk alleles, high iron intake was associated with increased risk of IA with insulin as first autoantibody [adjusted hazard ratio (HR, 95% CI): 1.71 (1.14; 2.58), as compared to moderate iron intake.

Conclusions

Iron intake may alter the risk of islet autoimmunity in children with high-risk HLA haplogenotypes.