Status of Hemoglobin A1c Measurement and Goals for Improvement: From Chaos to Order for Improving Diabetes Care

Abstract

BACKGROUND:The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) established the importance of hemoglobin A 1c (Hb A 1c ) as a predictor of outcome in patients with diabetes mellitus. In 1994, the American Diabetes Association began recommending specific Hb A 1c targets, but lack of comparability among assays limited the ability of clinicians to use these targets. The National Glycohemoglobin Standardization Program (NGSP) was implemented in 1996 to standardize Hb A 1c results to those of the DCCT/UKPDS. CONTENT:The NGSP certifies manufacturers of Hb A 1c methods as traceable to the DCCT. The certification criteria have been tightened over time and the NGSP has worked with the College of American Pathologists in tightening proficiency-testing requirements. As a result, variability of Hb A 1c results among clinical laboratories has been considerably reduced. The IFCC has developed a reference system for Hb A 1c that facilitates metrological traceability to a higher order. The NGSP maintains traceability to the IFCC network via ongoing sample comparisons. There has been controversy over whether to report Hb A 1c results in IFCC or NGSP units, or as estimated average glucose. Individual countries are making this decision.

Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading

“…This provides consistency and comparability across a variety of clinical laboratories, allowing patients with diabetes to be treated to standardized targets. 2 When measured in an NGSP-certified laboratory, a change in A1c of at least 0.5 % is considered both statistically and clinically significant. 2 Separately Table 1 shows a comparison between A1c reported in NGSP and IFCC-derived values.…”

“…2 When measured in an NGSP-certified laboratory, a change in A1c of at least 0.5 % is considered both statistically and clinically significant. 2 Separately Table 1 shows a comparison between A1c reported in NGSP and IFCC-derived values. 1 Over the past several years, there has been expanded use of point-of-care (POC) assays to measure A1c.…”

“…1 In 1993, the landmark Diabetes Control and Complications Trial (DCCT) demonstrated its importance as a predictor of diabetes-related outcomes, and the ADA started recommending specific A1c targets in 1994. 2 Other key studies, such as the United Kingdom Prospective Diabetes Study (UKPDS), have consistently demonstrated the correlation between A1c and diabetes complications and have reinforced currently recommended target values. 2,3 The role of the A1c broadened in 2010 when the ADA added A1c ≥6.5 % as a diagnostic criterion for diabetes, allowing the test to be used for both management and diagnosis.…”

“…2 Other key studies, such as the United Kingdom Prospective Diabetes Study (UKPDS), have consistently demonstrated the correlation between A1c and diabetes complications and have reinforced currently recommended target values. 2,3 The role of the A1c broadened in 2010 when the ADA added A1c ≥6.5 % as a diagnostic criterion for diabetes, allowing the test to be used for both management and diagnosis. 3 The value of 6.5 % was selected as an optimal cut point for detecting prevalent retinopathy consistent with the definition used for current fasting (≥126 mg/dL) and 2-h (≥200 mg/dL) plasma glucose cut points.…”

A new integrated tool for assessing and monitoring test comparability and stability

“…In particular, the laboratory has to verify the consistency of the manufacturer's declared performance during routine operations performed strictly in accordance with their instruction, and to participate in external quality assessment (EQA)/proficiency testing (PT) schemes structured so that they provide objective information on the analytical quality of measurements performed by clinical laboratories and on the performances of the peer group assays [5][6][7]. EQA programs using commutable materials and reference method target values are becoming more widespread, but until now they are applied only to few constituents (i.e., hemoglobin A 1c ) [8,9]. Generally, an EQA program for clinical biochemistry on serum, performed by an independent national or regional center, with a sufficient number of participants so that the peer groups can be well defined, consists in a panel of about 25-35 measurands.…”