HbA1c and Glycated Hemoglobin
What are Glycated Hemoglobins?
Glycated hemoglobins arise from the non-enzymatic attachment of glucose to hemoglobin. They are formed and accumulate in the red cell in proportion to the blood glucose level. Their concentration reflects the long-term average glucose level and is thus useful as an indicator of diabetic control. The formation of HbA1c proceeds via a Schiff base adduct, or aldimine, followed by the Amadori rearrangement to form the stable ketoamine, HbA1c. The aldimine intermediate is often referred to as labile HbA1c and the rate of its conversion to the ketoamine is some 60 times slower than the reverse dissociation with release of the glucose.
What is Hemoglobin?
Hemoglobin is the red blood protein that transports oxygen from the lungs to the tissues. It is the major component of the red cell. Because the life of the red cell averages some 120 days, the extent that the hemoglobin is glycated can be used as an indication of the average glucose level over the previous one or two months.
A molecule of hemoglobin is made up of 4 protein chains. There are 2 alpha chains and 2 beta chains, usually denoted as α2β2. Glucose will react and bond to certain positively charged chemical groups on the hemoglobin. These are located at the start (N-terminal end) of each of the α and β chains and on some amino acid side chains within the protein. In particular glucose reacts with the ε-amino group of lysine amino acids.
What is the difference between HbA1c and Glycated Hemoglobin?
Glycated hemoglobin is defined as hemoglobin with glucose bound to any of these potential sites. HbA1c is a subset of glycated hemoglobins. It is defined as hemoglobin with glucose bound at the beginning (N-terminal) of the β-chain. The total glycated hemoglobin will include HbA1c plus all the other hemoglobins that have glucose bound to lysine side chains and/or to the N-terminal of the α-chain. Generally about half of the glucose is bound to the HbA1c position with the other half bound at 3 or 4 other sites (lysines).