Study Finds Significant Association Between Iron Intake, Slowed T1D Progression

Among children with increased risk of islet autoimmunity (IA) and type 1 diabetes (T1D) progression, higher iron intake at the time of IA seroconversion was found to be associated with a lower risk of progression to T1D, independent of multivitamin supplement use.

These findings were published in Frontiers in Immunology and are based on data from DAISY, a prospective cohort from 1993-2004 that included 2547 children in Colorado at high risk for developing T1D.

“Studies of the role of iron in the risk of type 1 diabetes (T1D) have been inconsistent,” the authors explained. “Given that iron generates reactive oxygen radicals, which can lead to oxidative damage and apoptosis in the beta cells of the pancreas, we examined whether iron intake was associated with the risk of progressing to T1D in individuals with islet autoimmunity (IA), the pre-clinical phase of T1D.”

IA is defined as the presence of 2 or more consecutive serum samples positive for at least 1 autoantibody, such as insulin, GAD, IA-2, or ZnT8. In the study, the authors assessed the dietary intake of 175 children with IA at the time of seroconversion. Of this group, 64 children eventually progressed to T1D.

When analyzing the relationship between energy-adjusted iron intake and the risk of progression to T1D, the authors also accounted for factors such as HLA-DR3/4 genotype, race and ethnicity, age at seroconversion, presence of multiple autoantibodies at seroconversion, and use of multiple vitamins. Children who progressed to T1D were more likely to be non-Hispanic white, have the high-risk HLA genotype, be younger at the time of the seroconversion visit, and have multiple positive autoantibodies at the seroconversion visit, compared with children who did not progress to T1D.

In this study, high iron intake was defined as above the 75th percentile, or >20.3 mg/day, and moderate iron intake was defined as the middle 25-75th percentiles, or 12.7-20.3 mg/day.

The National Institutes of Health’s recommended daily allowance (RDA) for iron consumption through food and supplements is 13.7-16.3 mg per day in children and young adults aged between 2 and 19 years, which falls in the moderate intake category of the study. Children in the high intake category had iron intake just above the RDA levels.

In the United States, iron intake from food alone is 11.5-13.7 mg for children aged between 2 and 11 years, and 15.1 mg for children aged between 12 and 19 years. In this study, the interquartile range of iron intake from foods was 11.8-15.4 mg, suggesting the children in the DAISY study were not consuming a large amount of iron.

The adjusted analysis demonstrated a significant association between high iron intake and decreased risk of progression to T1D, with the risk of progression to T1D being nearly 70% lower in the high iron intake group than in the moderate intake group (HR, 0.31; 95% CI, 0.14-0.72; P = .0065).

Interestingly, this found association opposed the authors’ a priori hypothesis. Because of this, they explored a potential alternate hypothesis that high iron intake may be representing another factor, as the children in the high iron intake category were more likely to use multiple vitamin supplements. In the high iron intake group, 39 (88%) children were taking multiple vitamins compared with 34 (38%) children in the moderate intake group and 14 (33%) children in the low intake group.

According to the authors, this suggested that the association between iron intake and reduced T1D risk could be influenced by the use of multiple vitamin supplements. However, after accounting for multiple vitamin use, high iron intake was still significantly associated with decreased risk of progression to T1D compared with moderate iron intake (adjusted HR, 0.35; 95% CI, 0.15-0.79).

When they tested whether the association between iron intake and T1D progression was influenced by vitamin C or calcium intake, the authors also found that neither of these factors had an effect. A sensitivity analysis also showed that the removal of 6 children from the study who received a celiac disease diagnosis prior to IA seroconversion did not affect this association.

“It is possible that our observation that high iron intake was associated with a decreased risk of progression to T1D might be due to the healthier lifestyle habits of children reporting higher intakes of iron, the authors noted. “Future studies using iron status biomarkers, such as serum ferritin, will be helpful in investigating iron as a risk factor for the progression of T1D and any unknown aspects of this relationship.”

Reference

Elhassan S, Dong F, Buckner T, et al. Investigating iron intake in risk of progression from islet autoimmunity to type 1 diabetes: The diabetes autoimmunity study in the young. Front Immunol. Published online March 28, 2023. doi:10.3389/fimmu.2023.1124370