Clinical Significance

Hemoglobin (Hb) consists of four protein subunits, each containing a heme moiety, and is the red-pigmented protein located in the erythrocytes. Its main function is the transport of oxygen and carbon dioxide in blood. Each Hb molecule is able to bind four oxygen molecules. Hb consists of a variety of subfractions and derivatives. Among this heterogeneous group of hemoglobins HbA1c is one of the glycated hemoglobins, a subfraction formed by the attachment of various sugars to the Hb molecule.

HbA1c is formed in two steps by the non-enzymatic reaction of glucose with the N-terminal amino group of the β-chain of normal adult Hb (HbA). The first step is reversible and yields labile HbA1c. This is rearranged to form stable HbA1c in a second reaction step. In the erythrocytes, the relative amount of HbA converted to stable HbA1c increases with the average concentration of glucose in the blood. The conversion to stable HbA1c is limited by the erythrocyte's life span of approximately 100 to 120 days.

As a result, HbA1c reflects the average blood glucose level during the preceding 2 to 3 months. HbA1c is thus suitable to monitor long-term blood glucose control in individuals with diabetes mellitus. Glucose levels closer to the time of the assay have a greater influence on the HbA1c level. The risk of diabetic complications, such as diabetic nephropathy and retinopathy, increases with poor metabolic control.

In accordance with its function as an indicator for the mean blood glucose level, HbA1c predicts the development of diabetic complications in diabetes patients. For monitoring long term glycemic control, testing every 3 to 4 months is generally sufficient. In certain clinical situations, such as gestational diabetes, or after a major change in therapy, it may be useful to measure HbA1c in 2 to 4 week intervals.