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.

HbA1c measurement in diabetes diagnosis and management of diabetes in latin: proceedings of the San Pablo Symposium

“…Application of this model in several European countries and in the US demonstrated the current general status of HbA1c assays and whether they meet the quality targets set by the IFCC Task Force 52 . The general picture allows comparison of the performance of various analytical principles and commercial versions 53 .…”

In vitro determination of hemoglobin A1c for diabetes diagnosis and management: technology update

“…The most common analytical interferences are hemoglobin variants, elevated HbF, and hemoglobin adducts. 42 …”

Analysis and Quantitation of Glycated Hemoglobin by Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry

“…Hemoglobin molecules modified elsewhere (e.g., other primary amines on lysine side chains) and most hemoglobin genetic variants are detectable using these methods, but often these species display different retention properties, and this can compromise accurate quantification of both the βHb and HbA1c peaks [25][26][27]. Existing methods are not designed to detect other glycated hemoglobin species and can yield inaccurate results if patients express variant hemoglobin forms [28,29].…”