Translating Hemoglobin A1c into Average Blood Glucose: Implications for Clinical Chemistry

Abstract

Measurement of hemoglobin A1c (Hb A1c)1 is a fundamental component of the management of patients with diabetes mellitus. Hb A1c measurement provides an indication of chronic exposure to glucose and is extensively used for both monitoring long-term glycemic status and evaluating whether an individual patient has attained adequate metabolic control. The patient’s Hb A1c value is used by clinicians to determine whether glucose-lowering therapy is adequate. A recent report (1) establishes a mathematical relationship between Hb A1c and the average glucose (AG) concentration in blood. The findings presented are likely to have considerable impact on the way Hb A1c is reported by clinical laboratories and used by healthcare providers (and patients). The importance and potential consequences of the study are the focus of this Perspective. The efficacy of therapy to lower blood glucose in patients with diabetes mellitus is assessed by 2 complementary methods, glucose measurement, which is performed by patients, and Hb A1c measurement. Patients perform self-monitoring of blood glucose (SMBG) by using hand-held meters to measure their own blood glucose concentrations. It is recommended that patients on insulin perform SMBG 4 times a day. The dose of the insulin injection is determined by the glucose value. Many modern meters store the results of all the glucose measurements, which can be downloaded and accessed by the physician during the patient’s visit. The second method for monitoring therapy to lower blood glucose is measurement of glycohemoglobin, most commonly performed by assaying Hb A1c. Glycohemoglobin is formed by the attachment of glucose to hemoglobin by a nonenzymatic process, termed glycation. The erythrocyte membrane is permeable to glucose, which enters the cell, where it binds to hemoglobin. The unstable product, termed an aldimine, undergoes an Amadori rearrangement to form a stable …