Transient elevations in blood glucose levels can lead to the production of large amounts of aldimines. If blood glucose levels return to normal, the response is reversed. However, since glucose remains bound to proteins until it is metabolized, the formation of ketamines is irreversible. This process is critical for understanding and interpreting assays that measure glycated proteins. Most of the existing methods for measuring glycosylated hemoglobin can only measure stable ketamines, but not the unstable parts (aldimines). Thus, these methods reflect long-term average blood glucose and are relatively immune to recent sharp fluctuations in blood glucose levels.
The hemoglobin formed in new red blood cells carries very little attached glucose into the circulation. However, glucose can permeate freely into red blood cells. Therefore, glucose is irreversibly attached to hemoglobin, and the rate of attachment depends on the current blood glucose concentration. About 1% of the red blood cells in the human body are destroyed every day, and the same number of new red blood cells are produced at the same time. Therefore, the average amount of A1C changes dynamically and is indicative of the average blood glucose concentration over the lifespan of the red blood cells. Although A1C theoretically reflects average blood glucose over the entire 120-day lifespan of red blood cells, it is most correlated with average blood glucose in the first 8-12 weeks.