The National Glycohemoglobin Standardization Program: Over 20 Years of Improving Hemoglobin A1c Measurement

BACKGROUND: Measurement of hemoglobin A1(c) (HbA(1c)) in the blood is integral to and essential for the treatment of patients with diabetes mellitus. HbA(1c) reflects the mean blood glucose concentration over the preceding 8 to 12 weeks. Although the clinical value of HbA(1c) was initially limited by large differences in results among various methods, the investment of considerable effort to implement standardization has brought about a marked improvement in analysis. CONTENT: The focus of this review is on the substantial progress that has been achieved in enhancing the accuracy and, therefore, the clinical value of HbA(1c) assays. SUMMARY: The interactions between the National Glycohemoglobin Standardization Program and manufacturers of HbA(1c) methods have been instrumental in standardizing HbA(1c). Proficiency testing using whole blood has allowed accuracy-based assessment of methods in individual clinical laboratories that has made an important contribution to improving the HbA(1c) measurement in patient samples. These initiatives, supported by the efforts of the IFCC network, have led to a continuing enhancement of HbA(1c) methods. Many of the factors that previously influenced HbA(1c) results independently of blood glucose have been eliminated from most modern methods. These include carbamylation, labile intermediates, and common hemoglobin variants. Nevertheless, some factors (e.g., race and aging) may alter HbA(1c) interpretation, but whether these differences have clinical implications remains contentious. HbA(1c) has a fundamental role in the diagnosis and management of diabetes. Ongoing improvements in HbA(1c) measurement and quality will further enhance the clinical value of this analyte. (C) 2019 American Association for Clinical Chemistry