Glycated hemoglobin (HbA1c): old dogmas, a new perspective?

The hemoglobin A1c (HbA1c) assay provides a reliable measure of chronic glycemia and correlates well with the risk of long-term diabetes complications, so that it is currently considered the test of choice for monitoring and chronic management of diabetes. Recently, HbA1c testing has been included within the diagnostic criteria recommended for diagnosis of diabetes in nonpregnant individuals by the American Diabetes Association (ADA). The emerging concept that HbA1c can be used rather than blood glucose in the diagnosis of diabetes is highly appealing for a variety of reasons, including less sensitivity to preanalytical variables, lower within subject biological variability, little to null interference from diurnal variations, acute stress and common drugs which are known to influence glucose metabolism, as well as the fact that one single measurement might provide information for both diagnosing diabetes and tracking glycemic control. On the other hand, the use of HbA1c for screening and diagnosing diabetes also carries some limitations, including the worse diagnostic performance in different populations (i.e., pregnancy, elderly and non-Hispanic blacks), the risk of overdiagnosis in subjects with iron deficiency anemia, in subjects genetically predisposed to hyperglycation, and in those with increased red blood cell turnover. There is also a higher risk of misdiagnosis in patients with end-stage renal disease and heavy alcohol consumption. Finally, HbA1c testing might be biased due to the interference from several hemoglobin variants, is characterized by a higher imprecision than blood glucose measurement, and is more expensive. This paper will critically summarize the potential advantages and limitations of HbA1c as a recommended test for diagnosing diabetes.