From the Guidelines
Iron deficiency anemia can cause an increase in Hemoglobin A1c (HbA1c) levels, even in patients without diabetes, due to the prolongation of erythrocyte life span and increased exposure to glucose. This occurs because iron deficiency leads to a reduction in the production of new red blood cells, resulting in an older population of circulating red blood cells. Since HbA1c measures the amount of glucose attached to hemoglobin over the lifespan of red blood cells (typically 120 days), older red blood cells have had more time to accumulate glucose, artificially elevating HbA1c values. According to a study published in the Annals of Internal Medicine in 2017 1, iron deficiency anemia is associated with falsely elevated HbA1c levels.
Key points to consider:
- Iron deficiency anemia prolongs erythrocyte life span, exposing the cell to glucose for a longer period, which can result in falsely elevated HbA1c levels 1.
- Conditions that shorten erythrocyte life span, such as hemolytic anemia, may result in falsely low HbA1c levels 1.
- Healthcare providers should consider checking iron studies when interpreting borderline HbA1c results, especially in patients with risk factors for iron deficiency such as menstruating women, pregnant women, or those with gastrointestinal blood loss.
- Treatment of the underlying iron deficiency with iron supplementation (typically ferrous sulfate 325mg daily or alternative iron formulations) for 3-6 months typically normalizes HbA1c levels. As noted in a study published in JAMA in 2006 1, any process that slows erythropoiesis, such as aplastic anemia, will increase HbA1c by causing an older erythrocyte cohort.
From the Research
Iron Deficiency Anemia and HbA1c Levels
- Iron deficiency anemia has been shown to affect Hemoglobin A1c (HbA1c) levels, with some studies indicating an increase in HbA1c levels in individuals with iron deficiency anemia 2, 3, 4, 5.
- A study published in the Annals of laboratory medicine found that treatment of iron deficiency anemia led to a significant increase in HbA1c levels 2.
- Another study published in the Turkish journal of medical sciences found that iron replacement therapy decreased HbA1c levels in anemic patients with type 2 diabetes 6.
- A review published in Diabetes & metabolic syndrome suggested that iron deficiency anemia may shift HbA1c levels slightly upward, although the exact mechanism remains unclear 3.
- A systematic review published in Diabetologia found that iron deficiency anemia led to an increase in HbA1c values compared to controls, with no concomitant rise in glucose indices 4.
Mechanism of Increased HbA1c Levels
- The exact mechanism by which iron deficiency anemia affects HbA1c levels is not fully understood, but it is thought to be related to changes in red blood cell turnover and the quality and heterogeneity of erythrocytes 3, 5.
- Iron deficiency may accelerate glycation by changing the structure of hemoglobin and inducing peroxidation 5.
- Hematological changes, iron metabolism, and study methodology may also affect the results of diagnostic investigations, leading to false results 5.
Clinical Implications
- Iron status should be considered when interpreting HbA1c concentrations in diabetes mellitus 6.
- The association between iron deficiency anemia and increased HbA1c levels may lead to confusion when diagnosing diabetes using HbA1c 4.
- Further studies are needed to fully understand the relationship between iron deficiency anemia and HbA1c levels, and to determine the clinical implications of this association 2, 3, 4, 5.