Interference of iron deficiency in glycated hemoglobin testing and its clinical implications

Introduction: Concentration of glycated hemoglobin (HbA1c) may be influenced by different types of anemia. This systematic review and meta-analysis aimed to evaluate the effect of iron deficiency anemia (IDA) and latent iron deficiency (LID) on HbA1c concentrations. Materials and methods: A search was conducted in Medline/PubMed, Web of Science, Embase, and LILACS up to May 2026. Eligible studies included cross-sectional, cohort, case-control, non-randomized intervention studies and clinical trials assessing the impact of IDA or LID on HbA1c concentrations. Methodological quality was evaluated using the ROBINS-I V2 tool for intervention studies and the Newcastle-Ottawa Scale for cross-sectional studies. Meta-analyses were performed using Review Manager 5 (The Cochrane Collaboration, Copenhagen, Denmark). Results: Among 43 studies evaluating IDA, 33 reported falsely elevated HbA1c concentrations. Of six studies assessing LID, two observed increased HbA1c concentrations. All four studies evaluating iron deficiency regardless of anemia status found elevated HbA1c. Among 19 intervention studies, 14 showed a reduction in HbA1c following iron supplementation. Meta-analyses including 30 studies confirmed increased HbA1c concentrations in patients with IDA (0.66% (0.31 to 1.00) or 7.21 mmol/mol (3.39 to 10.93), P < 0.001). Meta-analysis of four studies verified increased HbA1c in individuals with LID (0.66% (0.01 to 1.32) or 7.21 mmol/mol (0.11 to 14.43), P = 0.05). Meta-analysis of 14 intervention studies demonstrated a reduction in HbA1c following iron therapy (- 0.50% (- 0.92 to - 0.09) or 5.46 mmol/mol (- 10.05 to - 0.98), P = 0.02). Heterogeneity was mainly related to HbA1c assay methods and diagnostic criteria for anemia and iron deficiency. Conclusions: Iron deficiency anemia interferes with HbA1c measurement, leading to falsely elevated values, while LID may also increase HbA1c concentrations.