HbA1c: a review of analytical and clinical aspects

Abstract

After the relationship between glycemic control and the HbA1c concentration was demonstrated, many tests have been developed to determine the HbA1c concentration. The test results are standardized to the International Federation of Clinical Chemistry (IFCC) Reference Measurement Procedure (RMP) in harmony with the efforts of the National Glycohemoglobin Standardization Program (NGSP). The longitudinal use of the test requires strict quality management including accreditation of the laboratory, a dedicated internal control design, participation in an external quality assessment (EQA) program (proficiency test), and careful consideration of pre- and post-analytical aspects of the test. Performance goals for optimizing determination of the HbA1c concentration have been described. As an index of long-term glycemic control and a risk predictor, the HbA1c concentration is an indispensable part of routine management of diabetes. Because of the improving quality of the test, the HbA1c concentration is being increasingly applied in the diagnosis of diabetes. There are, however, concerns of this application in point-of-care settings. The HbA1c concentration is also used to achieve stringent control in pregnant diabetic patients. Strict standardization enables the definition of universal reference values and clinical decision limits. This review describes the present status of analytical and clinical aspects of determining the HbA1c concentration and highlights the challenges involved.

Keywords: Analytical aspects; Clinical aspects; Diabetes; HbA1c; Standardization.

Fig. 1

Analytical concepts of HbA1c measurement methods and their traceability to the IFCC-RMP. Abbreviations: IFCC, International Federation of Clinical Chemistry; RMP, Reference Measurement Procedure.

Fig. 2

Quality chain of IFCC-RMP-standardized HbA1c testing. The manufacturer uses calibrators, to which values have been assigned with the IFCC-RMP, to assign values to the kit calibrators. The EQA/PT provider uses samples also targeted by the IFCC-RMP. Good performance of the whole chain is demonstrated when the laboratory (clinical chemist), using the kit calibrators of the manufacturer, measures the correct HbA1c values in EQA/PT samples. Subsequently, all results of patients are traceable to the IFCC-RMP, and diabetologists can use universal reference values and decision limits. Abbreviations: IFCC-RMP, International Federation of Clinical Chemistry Reference Measurement Procedure; EQA, external quality assessment; PT, proficiency testing.

Fig. 3

The global distribution of reference laboratories operating the IFCC-RMP. Abbreviations: IFCC-RMP, International Federation of Clinical Chemistry Reference Measurement Procedure; US, the Unites States; BR, Brazil; NL, the Netherlands; D, Germany; F, France; I, Italy; IN, India; CN, China; KO, Korea; JP, Japan.