Glycosylated hemoglobin
Glucose is able to bind to a variety of structures, including hemoglobin (especially hemoglobin A1, in a non-enzymatic irreversible reaction. This process produces glycosylated hemoglobin (termed hemoglobin A1c). Initially, free intraerythrocyte glucose binds to hemoglobin producing a readily reversible Schiff-base intermediate (Amadori product), which then undergoes an irreversible rearrangement to a stable ketoamine derivative. When glucose concentrations are elevated in blood as in diabetes mellitus, there is increased binding of glucose to hemoglobin, which increases glycosylated hemoglobin values.
Glycosylated hemoglobin can be measured in the laboratory from whole blood (EDTA) samples by affinity chromatography (optimal technique), ion-exchange chromatography and colorimetric methods. When measured with chromatography, glycosylated hemoglobin in whole blood is stable for 7 days at 4 C and for 3 days at 25 C. When measured by thiobarbituric acid colorimetry, glycosylated hemoglobin is stable in whole blood for 21 days at 4 C and room temperature.
Factors influencing glycosylated hemoglobin
- Blood glucose concentration: Glycosylated hemoglobin concentrations are an indication of the average glucose concentration erythrocytes were exposed to over their lifespan. As erythrocyte lifespan is approximately 120 days in dogs and 65 days in cats, the glycosylated hemoglobin concentration is a reflection of the average glucose concentration over the preceding 3 to 4 months in dogs and 2 to 3 months in cats.
Therefore, glycosylated hemoglobin is an indicator of the blood glucose concentration over a longer period of time than either a single blood glucose measurement (which reflects the glucose concentration at the time of blood collection) or fructosamine concentrations.
- Changes in red blood cell mass: Anemia of any cause or animals with shortened red blood cell lifespan (e.g. hemolysis) will have decreased glycosylated hemoglobin concentrations. The reverse is true for polycythemic animals.
- Assay method: Cats have variable amounts of hemoglobin B as well as hemoglobin A. Ion-exchange chromatography methods are specific for hemoglobin A and may, therefore, underestimate glycosylated hemoglobin concentrations in cats. For this reason, affinity chromatography is preferred for measurement of glycosylated hemoglobin in cats.
Uses for glycosylated hemoglobin
- Diagnosis of diabetes mellitus: Glycosylated hemoglobin concentrations above reference intervals indicate a persistent hyperglycemia and are seen in diabetes mellitus.
Stress hyperglycemias will not elevate blood glucose concentrations for a long enough period of time to increase the glycosylated hemoglobin concentration.
However, animals with diabetes mellitus of only a few weeks duration may have glycosylated hemoglobin concentrations within reference intervals.
- Response to insulin therapy: Glycosylated hemoglobin can be used to monitor response to insulin therapy in diabetic patients, however fructosamine is probably better for this purpose as it will reflect changes in glucose concentration more rapidly than glycosylated hemoglobin.
|
