Measurement of Hemoglobin A1c

A new twist on the path to harmony

  1. David B. Sacks, MB, CHB, FRCPATH
  1. Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland
  1. Corresponding author: David B. Sacks, sacksdb{at}

Evaluation of glycemia is used for the diagnosis and management of patients with diabetes. Glucose and hemoglobin A1c (HbA1c) provide complementary information and both are used to assess an individual’s glycemic status. The concentration of glucose in the blood indicates the subject’s glycemia at the time of blood sampling. However, blood glucose concentrations are modified by numerous factors, ranging from food ingestion and exercise to stress and medication (1). By contrast, the concentration of HbA1c in the blood reflects the average glucose over the preceding 8–12 weeks. Thus, HbA1c provides an additional criterion for assessing glucose control that is free of the wide diurnal fluctuations that occur with blood glucose. HbA1c has several additional attributes, which render it valuable in the setting of diabetes. These include, but are not limited to, the following: the subject does not need to be fasting, blood can be sampled any time of the day, the sample is stable, and there is very little biological variability (1). These factors, in conjunction with the documentation that HbA1c predicts the development of microvascular (2,3) and macrovascular (4) complications of diabetes, have led to the widespread adoption of HbA1c as integral to the management of patients with diabetes. Guidelines from several prominent clinical organizations recommend that HbA1c be measured at regular intervals in all patients with diabetes (5,6).

The quality of analytical methods for HbA1c initially lagged considerably behind the evidence of its clinical value. Early assays lacked standardization, substantially limiting the use of HbA1c in patient care. Considerable effort was invested to effect standardization, with schemes developed in the 1990s in Japan (7), Sweden (8), and the U.S. (9). All HbA1c results were reported as a percentage of hemoglobin. The subsequent …

| Table of Contents