How long after initiating or adjusting treatments that affect red blood cell (RBC) turnover, such as iron supplements or erythropoiesis-stimulating agents, should a patient with diabetes or at risk for diabetes wait before rechecking Hemoglobin A1c (HbA1c) levels for an accurate reflection of their average blood glucose levels?

How Long to Wait Before Rechecking HbA1c After Treatments Affecting Red Blood Cell Turnover

Wait 2-3 months before rechecking HbA1c after initiating treatments that affect red blood cell turnover, as this is the timeframe required for HbA1c to accurately reflect average glycemia once red blood cell populations have normalized. 1

Understanding the HbA1c Timeframe

• HbA1c reflects average glycemia over approximately 2-3 months, which corresponds to the lifespan of red blood cells 1
• The American Diabetes Association specifically recommends measuring HbA1c every 3 months for patients whose therapy has changed or who are not meeting glycemic goals 1, 2
• This 3-month interval allows sufficient time for medication titration, dose optimization, assessment of patient adherence, and evaluation of lifestyle modifications 2

Impact of Treatments Affecting Red Blood Cell Turnover

Iron Supplementation and Erythropoiesis-Stimulating Agents

• Conditions that affect red blood cell turnover—including use of drugs that stimulate erythropoiesis, recent blood transfusion, hemolytic anemia, and other anemias—can interfere with the accuracy of HbA1c 1
• Research demonstrates that HbA1c falls following treatment with both parenteral iron (from 57 mmol/mol to 53 mmol/mol) and erythropoiesis-stimulating agents (from 56 mmol/mol to 49 mmol/mol) despite mean blood glucose remaining unchanged 3
• Iron deficiency anemia itself can elevate HbA1c concentrations independent of glycemia, with one study showing elevated HbA1c (6.8 ± 1.4%) in iron-deficient individuals compared to controls 4

Red Blood Cell Lifespan Variability

• Normal red blood cell lifespan ranges from 55-67 days, but can extend to 72-100 days in certain conditions, which directly impacts HbA1c accuracy 5, 6
• Research shows that the absolute difference between adjusted HbA1c (accounting for RBC lifespan) and laboratory HbA1c can be 3.9-5.3 mmol/mol [0.4-0.5%], which is clinically significant 6

Practical Recommendations for Timing

Standard Approach

• Recheck HbA1c 3 months after initiating iron supplements or erythropoiesis-stimulating agents to allow for red blood cell population turnover and stabilization 1, 2
• This quarterly testing interval is the optimal frequency to maximize downward trajectory in HbA1c and assess treatment effectiveness 7

Alternative Monitoring During the Transition Period

• In patients with conditions that interfere with HbA1c interpretation, use alternative approaches including self-monitoring of blood glucose, continuous glucose monitoring (CGM), fructosamine, or glycated albumin 1
• Unlike HbA1c, glycated albumin and fructosamine levels do not change following iron or erythropoiesis-stimulating agent therapy and may better reflect actual glycemic control during this transition period 3
• Fructosamine or CGM can be used for glycemic monitoring when an alternative to HbA1c is required 1

Common Pitfalls to Avoid

• Do not check HbA1c too early (before 2-3 months) as it may not reflect the full treatment effect and could lead to premature medication adjustments 2
• Avoid using HbA1c as the sole basis for treatment decisions in patients recently started on iron or erythropoiesis-stimulating agents, particularly if the result is close to a threshold that might prompt medication changes 1
• Do not delay the 3-month recheck beyond the recommended timeframe, as testing less frequently than quarterly is associated with deteriorating diabetes control and a significant detrimental effect on glycemic management 7
• Consider that HbA1c may underestimate glycemic control during the initial weeks after starting iron supplementation (when iron deficiency falsely elevated HbA1c) or may overestimate control after starting erythropoiesis-stimulating agents (when increased RBC production temporarily lowers HbA1c) 3, 4

When to Use Alternative Markers

• If immediate assessment of glycemic control is needed before the 3-month mark, use fructosamine (reflects 2-3 week average), glycated albumin (reflects 2-3 week average), or CGM metrics such as time in range 1, 3
• These alternative markers are not affected by red blood cell turnover and provide more accurate glycemic assessment during the transition period 3