Diagnostic Application of the A1c Assay in Renal Disease

A recent International Expert Committee, jointly appointed by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation, now advocates the use of glycated hemoglobin, measured by A1c assay, for diagnosing diabetes in nonpregnant individuals.1 Their recommendations suggest the diagnosis of diabetes when the A1c level is >6.5%, confirmed on repeat testing when patients are asymptomatic. In addition, patients with an A1c between 6.0 and 6.5% should be considered high risk, analogous to the state of prediabetes defined by either impaired fasting glucose or glucose tolerance. The rationale for this new approach emphasizes the advantages of the A1c assay over current diagnostic measures for accuracy, precise measurement of chronic glycemia, correlation with diabetic complications, and logistical ease of use. This proposal is under consideration by diabetic associations for possible implementation but lacks analysis of the validity of the A1c assay for diagnosing diabetes in the setting of renal impairment and renal replacement therapy (RRT). Hemoglobin A1c is the product of a nonenzymatic reaction between circulating hemoglobin and glucose. In the normal 120-day life cycle of the average red blood cell, the magnitude of glycated hemoglobin is reflective of longitudinal exposure to glucose. Glycation rate can be influenced by temperature, pH, red cell turnover, hemoglobin concentration, glucose concentration, and length of exposure to glucose.2 The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), conducted of patients with type 1 and type 2 diabetes respectively, were the pivotal studies demonstrating a link between A1c and diabetes-related complications.3,4 …