Hemoglobin A_1c Poised to Become Preferred Test for Diagnosing Diabetes

Measuring hemoglobin A_1c (HbA_1c) levels, a method to monitor glucose control in patients with diabetes, appears to be on the threshold of official recognition as the preferred diagnostic test for the disease.

The American Diabetes Association (ADA), along with the European Association for the Study of Diabetes and the International Diabetes Federation, will likely propose using HbA_1c as the preferred diagnostic test when revised recommendations are published later this year (American Diabetes Association. Diabetes Care. 2009;32[suppl 1]:S13-S61]).

Unofficially, some primary care physicians have been using the HbA_1c measurement to diagnose diabetes because the assessments currently recommended for diagnosis, fasting plasma glucose and oral glucose tolerance tests, are viewed as burdensome to patients. HbA_1c testing was not endorsed as a diagnostic and screening tool when the latest recommendations were published in 2003. At that time the internation expert committee, involving the ADA, said that clinical laboratories lacked standardization for HbA_1c measurement, and that the test lacked sufficient sensitivity.

Now, however, many diabetes experts have become convinced that under the direction of the National Glycohemoglobin Standardization Program, consistency efforts have improved HbA_1c measurement and that it is time for it to become a screening and diagnostic tool. As of September 2007, certification from the National Glycohemoglobin Standardization Program required manufacturers to produce tests that result in readings that are mostly within ±0.85% of true HbA_1c levels from 4% to 12%.

The best part of using HbA_1c testing, said Christopher Saudek, MD, professor of medicine at Johns Hopkins University School of Medicine in Baltimore, is its ease of use, which should facilitate diagnosing more patients with diabetes earlier in the course of the disease, when interventions are most successful.

“Probably up to 40% of people with diabetes are undiagnosed, and one reason would be that the test used most to diagnose diabetes requires fasting,” said Saudek, who was a member of an expert committee that issued a 2008 consensus statement calling for adoption of HbA_1c as a screening and diagnostic test for diabetes (Saudek CD et al. J Clin Endocrinol Metab. 2008;93[7]:2447-2453).

The committee recommended that screening standards be established to prompt further testing and closer follow-up, including HbA_1c exceeding 6.0%, a fasting plasma glucose of 100 mg/dL or greater, or a random plasma glucose of 130 mg/dL or greater. The members also said an HbA_1c of at least 6.5%, confirmed by a plasma glucose–specific test, should establish a diabetes diagnosis. The committee said as a screening test, an HbA_1c reading greater than 6.0% would produce a reasonable 63% to 67% sensitivity, with specificity adequately high (about 98%) to avoid an undue burden of false-positive tests.

However, the cutoff point for diagnosing diabetes using HbA_1c will probably remain in debate from both a clinical and societal point of view, said Mayer B. Davidson, MD, a professor of medicine at Charles R. Drew University in Los Angeles.

“Glucose impairment runs on a continuum, so where do you draw the line to say this is a disease—it is arbitrary,” Davidson said. “In our society, if you have a diagnosis of diabetes, you have a problem with medical insurance, so I draw the line higher. I may miss some, but I pick them up later.”

Davidson and colleagues argued in a 2007 article in favor of using HbA_1c testing that defined a value of 6.0% or less as normal, a value of 6.1% to 6.9% as indicating prediabetes, and a value of 7.0% or greater as indicating diabetes (Buell C et al. Diabetes Care. 2007;30[9]:2233-2235).

“It's about time that the national recommendations recognize the value of the HbA_1c test for screening and diagnosis,” said Daniel Einhorn, MD, vice president of the American Association of Clinical Endocrinologists and medical director of the Scripps Whittier Institute for Diabetes in La Jolla, Calif.

As for using HbA_1c as a screening tool, Einhorn said, “I hope that everyone with a risk factor—a family history of diabetes, obesity, hypertension— will know their [HbA_1c] and will be followed over time. We also think [the test] will bring more people at risk to the attention of their primary practitioner.”