Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study

Diabetes Care. 2023 May 1;46(5):1014-1018. doi: 10.2337/dc22-1359.

Abstract

Objective: To examine whether 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 GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.

Conclusions: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / genetics
  • Autoimmunity / genetics
  • Child
  • Diabetes Mellitus, Type 1*
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Iron
  • Iron Overload* / genetics
  • Iron, Dietary
  • Islets of Langerhans*
  • Risk Factors

Substances

  • Iron, Dietary
  • Iron
  • Autoantibodies