Hemoglobin A comprises the majority of normal adult hemoglobin (Hb) and includes the minor hemoglobins, Hb A1a, Hb A1b, and Hb A1c. Sometimes these three are referred to as Hb A1 but A1C is the major fraction and composes 80% of Hb A1. Following synthesis of Hb A, a nonenzymatic reaction adds glucose to the N-terminal valine on either beta chain forming glycated Hb. The pre-A1C molecule is a labile Schiff base and this reaction is reversible.
As the red blood cells circulate, an irreversible Amadori rearrangement of the pre-A1C base occurs forming a stable ketoamine, A1C. Over the life span of the red blood cells (120 days) this process continues and the concentration of A1C is proportional to the concentration of the blood glucose. The concentration of A1C then relates to an individual's average glucose over time and can be used as an index relating to the extent of carbohydrate control during a 2 - 3 month period.
There is also a direct relationship between the concentration of HbA1C and risk of complications in diabetic patients. Therefore, the ADA has recommended using HbA1C measurements to monitor glycemic control.
