Iron Deficiency, Iron Deficiency Anemia, and HbA1c Levels in Nondiabetic Adults: A Systematic Review and Meta-Analysis.

Iron deficiency refers to depleted body iron stores, while iron deficiency anemia (IDA) develops when iron depletion becomes sufficient to impair hemoglobin production. Both conditions may influence glycated hemoglobin (HbA1c) independently of circulating glucose and may therefore affect glycemic classification in adults without diabetes. This systematic review and meta-analysis evaluated the association of iron deficiency and IDA with HbA1c levels, while also examining anemia severity, iron-status markers, the effects of iron replacement, and the potential for HbA1c-based glycemic misclassification. PubMed/MEDLINE and Scopus were searched from inception to the final search, supplemented by Google Scholar and citation tracking. Eligible observational and before-and-after studies included adults without established diabetes and reported HbA1c in relation to iron status. Two reviewers independently performed study screening and data extraction. Risk of bias was assessed using Joanna Briggs Institute tools appropriate to each analytical component. Twenty-five reports were included, representing 24 independent populations. The primary meta-analysis did not establish a conclusive overall difference in HbA1c between participants with IDA and non-anemic controls, while the expanded sensitivity analysis suggested higher HbA1c in IDA but remained affected by substantial heterogeneity and methodological limitations. Individual studies reported inconsistent relationships between HbA1c, anemia severity, and iron-status markers. Most iron-treatment studies reported reductions in HbA1c after treatment, although some reported increases, and incomplete paired-data reporting prevented valid pooling. Evidence also suggested that IDA may contribute to HbA1c-based glycemic misclassification, particularly near diagnostic thresholds. Overall, the available evidence indicates that iron deficiency and IDA may affect HbA1c in adults without diabetes, although the direction and magnitude of this effect remain inconsistent. Accordingly, HbA1c warrants cautious interpretation when iron deficiency or anemia is present, especially when it is discordant with glucose-based testing.

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