Iron deficiency anemia and sickle cell disease can falsely increase HbA1c in non-diabetics

The researchers found no significant effect in patients with megaloblastic anemia and the β-thalassemia trait. Treatment of iron deficiency anemia significantly reduced the HbA1c level, bringing it back to normal.

Worldwide, diabetes is one of the most common diseases with significant mortality and morbidity. For the disease's diagnosis and monitoring, HbA1c remains one of the most critical methods. Since HbA1c reflects glucose attached to red blood cells, factors affecting the half-life of red blood cells (RBCs) and hemoglobin can influence HbA1c measurements.

Basil A Alzahrani from King Saud Bin Abdulaziz University for Health Sciences in Jeddah, Saudi Arabia, and colleagues aimed to assess the effect of different anemia types, including sickle cell anemia, iron deficiency anemia, megaloblastic anemia, and β -thalassemia trait on HbA1c levels in a tertiary hospital over the past six years (2016-2022).

For this purpose, they conducted a retrospective chart review of 324 patients with one of the four anemia types mentioned above and a control group. The control group comprised healthy adults with normal hemoglobin and HbA1c who were unaware of anemia or diabetes. Patients with prediabetes or diabetes based on elevated fasting or self-reporting, random blood sugar, or 2 hours post-prandial blood glucose were excluded.

The study revealed the following findings:

• The mean HbA1c levels were remarkably higher in iron deficiency anemia at 5.75% and in sickle cell anemia at 5.83% compared to the control group at 5.32%.
• In megaloblastic anemia, the mean HbA1c levels were 5.38% and 5.45% in the beta thalassemia trait, which was not significantly different from the control group.
• HbA1c notably decreased from 5.75 to 5.44% after treatment in the iron-deficient group.
• Higher red cell distribution width and lower hemoglobin corresponded with higher HbA1c levels in patients with sickle cell anemia.

To conclude, sickle cell disease and iron deficiency anemia (IDA) can falsely increase HbA1c and anemia correction in IDA patients can lower the level back to baseline.

"Our study found an inverse relation between hemoglobin level and HbA1c level in sickle cell anemia patients, while high red cell distribution width (RDW) corresponded with high HbA1c levels," the researchers wrote. "When depending on HbA1c for diabetes diagnosis in those with sickle cell disease and IDA, clinicians should use caution."

"We recommend anemia correction in IDA patients before HbA1c use for diagnostic purposes. Further studies on a larger scale are required to assess the effect of sickle cell disease and red cell distribution width on HbA1c."

Reference:

Alzahrani, B.A., Salamatullah, H.K., Alsharm, F.S. et al. The effect of different types of anemia on HbA1c levels in non-diabetics. BMC Endocr Disord 23, 24 (2023). https://doi.org/10.1186/s12902-023-01280-y