From the Guidelines
A1C levels can be significantly affected by low hemoglobin, leading to potentially inaccurate results. When hemoglobin is low (anemia), A1C results may be falsely elevated or decreased depending on the specific cause of anemia, as noted in 1. In iron deficiency anemia, A1C tends to be falsely elevated, while in hemolytic anemia or conditions with increased red blood cell turnover, A1C may be falsely lowered. This happens because A1C measures the percentage of hemoglobin that has glucose attached to it over the previous 2-3 months. Some key points to consider include:
- Conditions that affect red blood cell turnover, such as hemolytic and other anemias, can result in discrepancies between the A1C result and the patient’s true mean glycemia, as discussed in 1.
- Hemoglobin variants must be considered, particularly when the A1C result does not correlate with the patient’s CGM or SMBG levels, as mentioned in 1.
- For patients with anemia, alternative methods to monitor blood glucose may be more accurate, such as fructosamine tests, glycated albumin, or more frequent blood glucose monitoring.
- If you have both low hemoglobin and diabetes, it's essential to treat the underlying cause of anemia while continuing to monitor your diabetes through multiple methods, as suggested in 1. Your healthcare provider may need to interpret your A1C results with caution and consider your hemoglobin levels when making treatment decisions, taking into account the limitations of A1C measurements, as highlighted in 1.
From the Research
Effect of Low Hemoglobin on A1c
- Low hemoglobin levels can affect A1c measurements, as A1c is a measure of the average blood glucose levels over the past 2-3 months, and hemoglobin is the protein in red blood cells that carries oxygen 2.
- Studies have shown that hemolysis, or the breakdown of red blood cells, can cause a decrease in A1c levels, but not in glycated albumin or 1,5-anhydroglucitol levels 2.
- Iron deficiency anemia, which can cause low hemoglobin levels, has also been shown to affect A1c levels, and treatment of iron deficiency anemia can decrease A1c levels in anemic patients with type 2 diabetes 3.
Mechanisms of A1c Measurement
- A1c measurements can be affected by the lifespan of red blood cells, as well as the rate of glucose uptake by red blood cells 4.
- A kinetic model of glucose levels and hemoglobin A1c has been developed, which takes into account red blood cell turnover, cross-membrane glucose transport, and hemoglobin glycation processes 4.
- This model has been shown to provide a more accurate estimation of laboratory A1c levels than estimated A1c from continuous glucose monitoring 4.
Clinical Implications
- HbA1c may not accurately reflect mean glucose levels in patients with certain conditions, such as hemolysis or iron deficiency anemia [(2,3)].
- Fructosamine, a measure of glycated albumin, may be a more accurate reflection of glycemic status in patients with these conditions 5.
- Continuous glucose monitoring or fructosamine may be used to complement HbA1c measurements and increase the accuracy of glycemic monitoring in certain patient populations 5.