Which of the following are limitations of HbA1c testing?

• A. Anemia
• B. Hemoglobin variants
• C. All of the above
• D. Renal disease

Answer: (C)

HbA1c reflects average glucose over the life of a red blood cell, about 120 days, so it relies on normal red cell turnover and standard hemoglobin. Anemia can alter red cell lifespan and the mix of younger versus older cells, biasing HbA1c in either direction. Hemoglobin variants can interfere with how the assay detects glycated hemoglobin, leading to falsely high or low results depending on the method. Renal disease often comes with anemia and other changes in red cell dynamics and treatment that shift HbA1c independently of actual glycemia, reducing reliability. Because these factors can all distort HbA1c, all of these are limitations of the test, and alternative markers or monitoring methods should be considered when accuracy is a concern.