A1C may be artificially high

Because hemoglobin glycation is sustained throughout the lifespan of the RBC, HbA1c depends not only on average blood glucose concentrations but also on the RBC lifespan, which averages about three months. Assuming normal RBC turnover, HbA1c thus represents the average blood glucose concentration over the previous three months. However, several variables can cause one to have RBC turnover rates which deviate significantly from this 3-month average. For instance, if an individual is iron deficient, anemic, or has had their spleen removed, they will have reduced RBC clearance and a longer RBC lifespan, thus artificially increasing HbA1c. Indeed, in patients with untreated iron-, vitamin B12-, or folate-deficiency anemia, iron or B-vitamin supplementation alone can reduce HbA1c by 0.3-1.0% with no other intervention (e.g., a drop from say, an HbA1c of 6% to an HbA1c of 5%), demonstrating how dramatically this metric can be affected by factors other than blood glucose.⁶

On the other end of the spectrum, I have a patient who initially seemed to be prediabetic based on an HbA1c of 6.1%, which should correspond to an average blood glucose of 128 mg/dL. Yet this person’s continuous glucose monitoring (CGM) reported an average blood glucose of 94±13 mg/dl over 30 days, which should correspond to an HbA1c of just 4.9% – an indication that there was likely a cause other than glucose levels leading to a high HbA1c. These types of false positives or false negatives in prediabetic diagnoses are why we need to use better (if at times less convenient) testing methods.