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 A1c (HbA1c) 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 HbA1c results, measured by three different ion-exchange HPLC procedures. To maintain and document consistent HbA1c 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 HbA1c 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.

Fig. 1

Mean HbA_1c measured by the BHL for one very long term QC specimen (●) and six additional QC specimens measured for shorter periods to demonstrate consistency throughout the DCCT and EDIC. Each point represents the mean of 34–653 measurements during each year of use. For each point the CV was <3%.

Fig. 2

Difference in HbA_1c between the CHL and the BHL at different HbA_1c concentrations, expressed as the change from baseline, as represented by values from the DCCT Diamat (1987–1993).