Hemoglobin A1c Measurements over Nearly Two Decades: Sustaining Comparable Values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study

Abstract

Background: Clinical trials require assays that provide consistent results during the course of a study. The hemoglobin A_1c (HbA_1c) assay, a measure of chronic glycemia, is critical to the study of diabetes control and complications. Methods: The Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), required 20 years of consistent HbA_1c results, measured by three different ion-exchange HPLC procedures. To maintain and document consistent HbA_1c results measured in the DCCT and EDIC Central Biochemistry Laboratory, a backup laboratory used frozen hemolysates as long-term calibrators and a HPLC method with a single lot of Bio-Rex 70 resin. Results: Over 20 years, long-term quality-control values have remained constant. Four studies of nondiabetic ranges produced nearly identical values [mean (SD), 5.1 (0.5)%, 4.9 (0.3)%, 5.0 (0.4)%, and 5.0 (0.3)%]. Conclusion: The overall consistency of the HbA_1c assays during the 20-year course of the DCCT and EDIC has been critical in establishing the benefits of intensive therapy and in understanding the relationship between long-term glycemia and the development and progression of the complications of diabetes.