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Question: I have a patient with very poor blood glucose control, yet her glycated hemoglobin (A1C) is always less than 6%. Why should this be?
Answer: Glycated hemoglobin (A1C) is a normal hemoglobin molecule with glucose attached. Usually, the higher the prevailing glucose, the higher the A1C level.
Once glucose attaches, it persists for the life of the red blood cell, approximately 120 days. The A1C test is a clinical tool for assessing long-term glucose control. It is important to remember that A1C depends on a normal hemoglobin molecule with a normal red blood cell lifespan, and that it is an average of high and low glucose values that will offset each other.1
Thus, one explanation for a good A1C level of 6% accompanied by high blood glucose readings would be that the patient is having wide swings in blood glucose levels, but capturing only or predominantly the high values on her glucose meter. In the A1C test, the low blood glucose measures are negating the high ones, resulting in an excellent average glucose reflected in the normal A1C.
Also, hemoglobinopathies and hemoglobin variants can give false positive A1C levels, and results are assay dependent. Understanding the relationship between A1C and plasma glucose can be useful in setting goals for day-to-day testing. Each 1% change in A1C represents a change of approximately 35 mg/dl mean plasma glucose. (Mean blood glucose results are 10–15% lower. Most blood glucose meters are calibrated to read as plasma glucose.2) This relationship applies only to A1C methods certified as traceable to the Diabetes Control and Complications Trial.3
Another possible explanation would be any situation in which there is a higher-than-usual proportion of young red blood cells in the circulation that have not had time to build up high levels of A1C.4 This commonly occurs in a patient who has had a recent blood transfusion. It also would occur in an individual with hemolysis, where there is a breakdown of red blood cells, or in a patient with slow blood loss. In both instances, the body may replace lost blood with new blood cells that have not had time to build up A1C.
Finally, other practical examples of a good A1C despite poor glycemic control are patients treated for a deficiency of iron, B12, or folate—again, because this causes a preponderance of new red blood cells.
In any of the above situations, it is important to rely on the glucose
meter results and/or to obtain a glycated albumin level (fructosamine), which
assesses the amount of glucose attached to albumin. This protein has a shorter
lifespan than that of red blood cells (28 days versus 120 days). However, it
can be an effective tool in individuals for whom an A1C level is not
reliable.5
Footnotes
The National Glycohemoglobin Standardization Program (NGSP) provides information about standardized A1C testing at http://www.missouri.edu/~diabetes/ngsp/index.html.
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References
2. American Diabetes Association: Tests of glycemia in diabetes (Position Statement). Diabetes Care 27 (Suppl. 1): S91–S93, 2004.
3. The Diabetes Control and Complications Trial Research Group: The
effect of intensive treatment of diabetes on the development and progression
of long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med 329:977–986, 1993.
4. Panzer S, Kronik G, Lechner K, et al.: Glycosylated hemoglobins
(GHb): An index of red cell survival. Blood 59: 1348–1350, 1982.
5. Armbruster DA: Fructosamine: Structure, analysis, and clinical
usefulness. Clin Chem 33:2153–2163, 1987.
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