Limitations of A1c Interpretation

Jessica G. Shepard, PharmD; Anita Airee, PharmD, BCPS; Andrew W. Dake, MD; M. Shawn McFarland, PharmD; Amit Vora, MD


South Med J. 2015;108(12):724-729. 

In This Article

Methods to Measure Hemoglobin A1c

Hemoglobin A1c (HbA1c) is the measurement of glycated hemoglobin. Glycation is an irreversible, nonenzymatic process that occurs when glucose binds to the N-terminus of the beta chain of the hemoglobin molecule. The rate of glycation is proportional to the concentration of glucose in the blood, and glycation increases with the age of the red blood cell.[10] Approximately 1% of red cells are destroyed every day, with an equal amount of new red cells regenerating. The A1c reflects the average blood glucose in the past 2 to 3 months, but approximately 50% of the A1c is determined by blood glucose levels during the preceding 1 month.[10,11]

There are several methods used to measure A1c that are approved by the NGSP. Most of these methods can be divided into two groups. The first group includes ion exchange and electrophoresis, which rely on the difference in charge to separate the hemoglobin from the glycated hemoglobin. The second group relies on differences in structure to separate the two species and includes affinity chromatography and immunoassay.[12] The immunoassay measures HbA1c specifically as the antibodies recognize the N-terminal glycated amino acids. There is no evidence to suggest that one method is superior to the others, but some patient conditions affect the A1c specific to the type of assay being used. Each year the College of American Pathologists assesses the compatibility values among assay methods. Published results are available that state the test and respective interfering measures.[13] Notably these results are used in evaluation of point-of-care devices as well and lend themselves to the same limitations.[14,15]