Interpreting A1C: Principles of the A1C Assay

Interpreting A1C: Principles of the A1C Assay

[music] DR. SACKS: Hemoglobin A1C, which is also called
A1C, is hemoglobin with glucose attached to the N-terminal valine of the beta-chain. Because red blood cells which contain the
hemoglobin live for approximately 120 days, hemoglobin A1C reflects the average glucose
over the preceding 8 to 12 weeks. For many years, blood glucose has been the
only way that diabetes could be diagnosed. The limitation of blood glucose is that to
diagnose diabetes, the patient has to be fasting. There are many other limitations. For example, it varies widely in a single
individual on different days. It can be affected by many factors such as
stress or exercise. And the sample is not stable, so once it’s
drawn, the blood has to be measured fairly soon or kept on ice. By contrast, hemoglobin A1C, because it reflects
average glucose over a few months, is not affected by ingestion of food. The sample can be drawn any time of the day;
the sample is stable. There is very little variation on different
days within an individual. There are certain factors that may interfere
with the measurement of hemoglobin A1C, the most common being variant hemoglobins which
may interfere with certain assays. A hemoglobin variant is hemoglobin with a
change in one of the amino acids that can result in a change in red cell life span or
can interfere with the assay depending on where the mutation occurs. Healthy people have hemoglobin A1C values
between 4 and 5.5. If the hemoglobin A1C value in a patient is
less than 3 or more than 15, the clinician should expect the presence of an interference. In this situation, the laboratory director
should be called and asked about the method used to measure hemoglobin A1C. Ideally, the blood sample should be measured
by a method that uses a different assay principle. For example, if the laboratory uses immunoassay,
an HPLC method should be used. It is very uncommon for an interference in
an assay to interfere with more than one assay method. The most common question I get is what to
do if I suspect the patient has a hemoglobin variant. In this situation, one should measure alternative
markers of long-term glycemia, for example, fructosamine or glycated albumin, which reflect
the average glucose over approximately the preceding three weeks. These are not affected by any changes in hemoglobin
or red cells because they measure the albumin in the blood. In addition, one should evaluate for the possible
presence of hemoglobin variant by performing hemoglobin electrophoresis or other analysis
that would identify a hemoglobin variant in the individual. Most subjects with common heterozygous hemoglobin
variants such as sickle cell trait are not aware that they have the condition at all. The key issues to remember about interpreting
hemoglobin A1C assays are that hemoglobin A1C is an integral component in the management
of patients with diabetes. Patients should have their hemoglobin A1C
measured at least every 6 months, and if the therapy is changed, it should be measured
more frequently, perhaps as often as every 3 months. [music]

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