November 2007: Volume 33, Number 11
Groups Issue Consensus Statement on HbA1c Standardization
By Deborah Levenson
A recent consensus statement from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and three diabetes groups calls for worldwide standardization of hemoglobin (HbA1c) test results through adoption of the IFCC reference method.
IFCC, the American Diabetes Association (ADA), the European Association for the Study of Diabetes and the International Diabetes Federation forged their statement—the result of years of negotiation—during a May 4 meeting in Milan. Their statement (Diabetes Care 2007; 30: 2399-2400) recognizes concurrence among the four organizations that HbA1c results reporting and the reference system on which it is based should be internationally standardized. The reference system previously published by members of an IFCC Working Group in 2002 (Clinical Chemistry 2002; 50: 166-174) is “the only valid anchor” for assessing patients’ glycemia, according to the statement, which notes agreement on three other points:
- Internationally, HbA1c results should be reported in IFCC units (mmol/mol) and derived National Glycohemoglo-bin Standardization Program (NGSP) units (%), using the IFCC-NGSP master equation.
- If the ongoing “average plasma glucose study” fulfills its a priori-specified criteria, an A1c-derived average glucose (ADAG) value calculated from the A1c result will also be reported as an interpretation of the A1c results.
- Glycemic goals appearing in clinical guidelines should be expressed in IFCC units, derived NGSP units, and as ADAG values.
In support of the move to report units for HbA1c in mmol/mol, the groups wrote, “Expressing test results in scientifically correct units along with a clinically relevant interpretation of those results is not an uncommon practice (e.g. creatinine and estimated glomerular filtration rate). Consequently, clinicians will have the opportunity to convey the concept of chronic glycemia in terms and units most suitable to patients under their care.”
What to Expect
The statement is unlikely to bring immediate, major changes to labs, physicians, and patients, noted David B. Sacks, MD, Associate Professor of Pathology, Harvard Medical School and Medical Director of Clinical Chemistry at Brigham and Women’s Hospital in Boston and Chair of the NGSP. “The IFCC reference system has been used for several years by manufacturers for calibration,” he explained. “The NGSP values, which are currently reported in a large part of the world, will continue to be used. In addition to this value, it is likely that estimated average glucose will be reported, and perhaps IFCC numbers in mmol/mol in some countries. It is important to realize that the instruments and methods used to measure patient samples will not change.”
Randie Little, PhD, Associate Professor of Pathology at University of Missouri School of Medicine in Columbia, Mo. and Coordinator of the NGSP Laboratory Network, added, “It’s unlikely that most methods will be able to report more than one result in the reasonably near future. So in the U.S. we will likely see only the percentage HbA1c, as we see now in most parts of the world. “
The ADAG Trial
That study on the relationship between average glucose and HbA1c has thus far yielded data that “establish a tight correlation,” between the two, according to co-principal investigator of the study, David M. Nathan, MD, Professor of Medicine at Harvard Medical School and Director of the Diabetes Center at Massachusetts General Hospital in Boston. Nathan’s comment reflects preliminary data from 427 patients from 10 centers in North America, Europe, and Africa. He also noted that the final data from the A1c-Derived Average Glucose (ADAG) trial, with a total of more than 600 patients enrolled, would be reported in the near future.
Nathan, who represented the ADA on the committee that wrote the consensus statement, called it a “reasonable compromise.” After final ADAG data are published, he expects the diabetes organizations to launch a major education campaign to promote the principles agreed upon in the statement.