Can iron deficiency or Chronic Kidney Disease (CKD) stage two cause Hemoglobin A1C (HbA1c) levels to be underestimated in a patient?

A1C Underestimation in Iron Deficiency and CKD Stage 2

Iron deficiency causes A1C to be falsely elevated (overestimated), not underestimated, while CKD stage 2 has minimal to no clinically significant effect on A1C accuracy.

Iron Deficiency Effects on A1C

Iron deficiency anemia prolongs red blood cell lifespan, exposing erythrocytes to glucose for extended periods, resulting in falsely elevated HbA1c levels that overestimate true glycemic control 1. This is the opposite of underestimation—your A1C will appear higher than your actual average glucose levels warrant.

Clinical Implications of Iron Deficiency:

• When iron deficiency is corrected through supplementation, HbA1c typically decreases by 0.5-0.7% as new red blood cells are formed with normal lifespans 2
• The American Diabetes Association recommends interpreting HbA1c with caution in patients with known or suspected anemia 1
• When HbA1c seems discordant with self-monitoring blood glucose results or clinical presentation, consider iron deficiency as a confounding factor 1

CKD Stage 2 Effects on A1C

CKD stage 2 (eGFR 60-89 mL/min/1.73 m²) has no clinically significant impact on A1C accuracy. The modest changes in the glucose-HbA1c relationship only become apparent with decreasing eGFR from 75 to 15 mL/min/1.73 m², and these changes are not clinically significant compared to wide inter-individual variability 2.

When CKD Does Affect A1C:

• CKD stages 3-4: Patients tend to have slightly higher glucose levels than expected for given HbA1c levels, meaning A1C may underestimate glycemia 2
• CKD stage 5/dialysis: The relationship becomes more complex with both falsely elevated and falsely decreased values possible 2, 3

Factors That Actually Cause A1C Underestimation

The following conditions cause A1C to underestimate true glycemic control:

• Reduced red blood cell lifespan from hemolysis or uremia 2, 4, 1
• Blood transfusions that introduce younger red blood cells 2, 4
• Hemolytic anemia that shortens erythrocyte survival 2, 1

Factors That Cause A1C Overestimation

Conversely, these conditions falsely elevate A1C:

• Iron deficiency anemia (as discussed above) 1
• Carbamylation of hemoglobin from uremia in advanced CKD 2, 4
• Metabolic acidosis in advanced CKD 2, 4

Practical Recommendations for Your Clinical Scenario

For a patient with iron deficiency:

• Expect A1C to overestimate glycemic control 1
• Use self-monitoring blood glucose or continuous glucose monitoring for more accurate assessment 1
• After iron repletion, anticipate A1C to drop 0.5-0.7% even without changes in actual glucose control 2

For a patient with CKD stage 2:

• Continue using A1C as the primary glycemic marker without adjustment 2
• HbA1c remains the best clinical marker of long-term glycemic control when combined with self-monitoring of blood glucose 2
• No alternative markers are needed at this stage of kidney disease 2

When to Consider Alternative Monitoring

Alternative markers like fructosamine, glycated albumin, or continuous glucose monitoring should be considered when 2, 1:

• eGFR falls below 30 mL/min/1.73 m² (CKD stages 4-5)
• Known anemia of any cause is present
• HbA1c values don't correlate with self-monitored glucose readings
• The glucose management indicator (GMI) from CGM differs from laboratory HbA1c by >0.5% 5, 3