Review of hemoglobin A1c in the management of diabetes

Hemoglobin HbA(1c) (A(1c)) has been used clinically since the 1980s as a test of glycemic control in individuals with diabetes. The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glycemic control, quantified by lower blood glucose and A(1c) levels, reduced the risk of the development of complications from diabetes. Subsequently, standardization of A(1c) measurement was introduced in different countries to ensure accuracy in A(1c) results. Recently, the International Federation of Clinical Chemists (IFCC) introduced a more precise measurement of A(1c), which has gained international acceptance. However, if the IFCC A(1c) result is expressed as a percentage, it is lower than the current DCCT-aligned A(1c) result, which may lead to confusion and deterioration in diabetic control. Alternative methods of reporting have been proposed, including A(1c)-derived average glucose (ADAG), which derives an average glucose from the A(1c) result. Herein, we review A(1c), the components involved in A(1c) formation, and the interindividual and assay variations that can lead to differences in A(1c) results, despite comparable glycemic control. We discuss the proposed introduction of ADAG as a surrogate for A(1c) reporting, review imprecisions that may result, and suggest alternative clinical approaches.