The long and winding road to optimal HbA1c measurement

Abstract

The importance of hemoglobin A1c (HbA1c) as an indicator of mean glycemia and risks for complications in patients with diabetes mellitus was established by the results of long-term clinical trials, most notably the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), published in 1993 and 1998 respectively. However, clinical application of recommended HbA1c targets that were based on these studies was difficult due to lack of comparability of HbA1c results among assay methods and laboratories. Thus, the National Glycohemoglobin Standardization Program (NGSP) was initiated in 1996 with the goal of standardizing HbA1c results to those of the DCCT/UKPDS. HbA1c standardization efforts have been highly successful; however, a number of issues have emerged on the "long and winding road" to better HbA1c, including the development of a higher-order HbA1c reference method by the International Federation of Clinical Chemistry (IFCC), recommendations to use HbA1c to diagnose as well as monitor diabetes, and point-of-care (POC) HbA1c testing. Here, we review the past, present and future of HbA1c standardization and describe the current status of HbA1c testing, including limitations that healthcare providers need to be aware of when interpreting HbA1c results.

Figure 1

Mean HbA1c measured by the CPRL for one very long term QC specimen and six additional QC specimens measured for shorter periods. Each point represents the mean of 34–653 measurements during each year of use. For each point the CV was <3%.

Figure 2

NGSP Network and Process: CPRL, Central Primary Reference Laboratory; PRL, Primary Reference Laboratory; SRL, Secondary Reference Laboratory

Figure 3

Mean of each method compared to the NGSP/DCCT target (dotted lines) in 1993, 1999, 2004, and 2012 based on CAP GH2 survey data. Symbols represent the mean; error bars are ±2SD.

Figure 4

CVs for all HbA1c results on the GH2 CAP surveys between 2000 and 2012 for samples with assigned HbA1c values of (A) 4–6%, (B) 6–8%, and (C) 8–10%. The bold solid line represents the trend line.