My daughter’s A1c is 6.6%, but her doctor thinks it should be higher according to her glucose readings. He suggested a test for sickle cell disease, saying this may be an explanation for the unusual low number, and we are awaiting the result. Is there any information about A1c test results being too low? What factors could cause that result?

Yes, a variety of things can cause a falsely high or falsely low hemoglobin A1c value. Most are uncommon.

It may be helpful to review the nature of the A1c. It is a measure of how much glucose is attached to hemoglobin; hence it is a measure of “glycohemoglobin.” Therefore not only can the absolute glucose values affect the number, but also the quantity and quality of hemoglobin. Hemoglobin gets “recycled” by the body roughly every 120 days, although, statistically at any moment, only one-half the hemoglobin has been glycosylated (because some hemoglobin is brand-new and does not yet have sugar stuck to it and some hemoglobin is just about to recycle and sugar is no longer attached). So anything that leads to short-lived red blood cells (that house the hemoglobin) can lead to a lower HbA1c value. Certain hemoglobin irregularities, such as sickle cell hemoglobin, can therefore lead to a lower HbA1c. It depends on the measurement technique. If there is a question, then your child’s “total glycohemoglobin” may need to be measured, not just the sub-fraction of A1c.

DS

[Editor’s comment: See Evaluation of HbA1c determination methods in patients with hemoglobinopathies Schnedl WJ, Krause R, Halwachs-Baumann G, Trinker M, Lipp RW, Krejs GJ., in Diabetes Care 2000 Mar;23(3):339-44.

SS]