630 The Clinical Use of Hemoglobin A 1 c Saudek

Hemoglobin A1c (HbA1c) has been accepted as an index of glycemic control since the mid-1970s and is the best marker for diabetic microvascular complications. Clinically, it is now used to assess glycemic control in people with diabetes. Assays are most reliable when certified by the National Hemoglobin Standardization Program but are subject to confounders and effect modifiers, particularly in the setting of hematologic abnormalities. Other measures of chronic glycemic control—fructosamine and 1,5-anhydroglucitol—are far less widely used. The relationship of HbA1c to average blood glucose was intensively studied recently, and it has been proposed that this conversion can be used to report an “estimated average glucose, eAG” in milligrams/deciliter or millimolar units rather than as per cent glycated hemoglobin. Finally, HbA1c has been proposed as a useful method of screening for and diagnosing diabetes. J Diabetes Sci Technol 2009;3(4):629-634 SYMPOSIUM Introduction The first description of hemoglobin A1c (HbA1c) has been variously ascribed to Kunkel1 or Huisman,2,3 but Rahbar, in 1969, is generally credited with the recognition of HbA1c as abnormal in diabetes.4 He noted “an unusual hemoglobin” in diabetes. Bunn et al.5 at Harvard, and Koenig et al.6 at the Rockefeller University, established the identity of HbA1c as chemical glycation of N-terminal lysine and valines of hemoglobin A. The chemical reaction includes an initial, reversible, formation of the aldehyde Schiff base, followed by essentially irreversible Amadori rearrangement to the stable ketoamine.5 Early on, we evaluated HbA1c in diabetes at the General Clinical Research Center at Cornell University Medical College.7 Before initiation of improved blood glucose control with insulin, the mean baseline fasting glycemia was 343 mg/dl, and the HbA1c was 9.8%. After 3 months of intensified diabetic control with insulin, the mean fasting blood glucose concentration was 84 mg/dl, and the HbA1c had dropped to 5.8%. That report, in 1976, suggested that, Hemoglobin A1c concentration appears to reflect the mean blood sugar concentration best over previous weeks to months. The periodic monitoring of hemoglobin A1c levels provides a useful way of documenting the degree of control of glucose metabolism in diabetic patients and provides a means whereby the relation of carbohydrate control to the development of sequelae can be assessed.7