ADA Officially Endorses HbA_1c for Diagnosis of Diabetes

The American Diabetes Association has officially endorsed the use of hemoglobin A_1c as an option for diagnosing diabetes.

In its Standards of Medical Care in Diabetes, updated annually, the ADA for the first time in 2010 is officially endorsing the use of HbA_1c as one of four options for diagnosing diabetes, with a cut-point of 6.5% or greater. Recommendations for use of the three previous diagnostic criteria remain unchanged, including a fasting plasma glucose (FPG) of 126 mg/dL or above, a 2-hour plasma glucose of 200 mg/dL or greater following a 75-g oral glucose tolerance test, or a random plasma glucose of 200 mg/dL or greater in an individual with classic symptoms of hyperglycemia (Diabetes Care 2010[suppl 1]:S11–61 [doi:10.2337/dc10-S011

In June 2009, the use of HbA_1c for diabetes diagnosis was endorsed in a consensus statement by an expert panel comprising members of the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation. However, that statement was not the official position of the respective organizations (Diabetes Care 2009;32:1327–34).

The new ADA endorsement is based in part on the fact that HbA_1c assays are now highly standardized, and “their results can be uniformly applied both temporally and across populations.” In addition, epidemiologic data show a relation between HbA1_c and the risk of retinopathy similar to that shown for corresponding FPG and 2-hour postprandial glucose thresholds. The HbA1_c is also more convenient since fasting is not required, and is likely to be more stable than glucose measurements, the statement said.

The ADA acknowledged that these advantages must be balanced by greater cost, limited availability of HbA_1c in some parts of the developing world, and incomplete correlation between HbA_1c and the average glucose in certain individuals. Also, the HbA_1c can be misleading in patients with certain forms of anemia and hemoglobinopathies. Indeed, unpublished data suggest that use of the HbA_1c with a cutoff of 6.5% or higher identifies one-third fewer cases of undiagnosed diabetes than does a FPG of 126 mg/dL or greater.

However, the ADA said, “in practice, a large portion of the diabetic population remains unaware of their condition. Thus, the lower sensitivity of A_1c at the designated cut-point may well be offset by the test's greater practicality, and wider application of a more convenient test (A_1c) may actually increase the number of diagnoses made.” (See sidebar for diagnostic criteria.)

Not everyone agrees. Dr. Zachary T. Bloomgarden of Mount Sinai School of Medicine, New York, said in an interview that while it may be appropriate to use HbA_1c as a screening tool to determine who would then be asked to return for an oral glucose tolerance test, using it for diagnosis is not appropriate because it could lead to overdiagnosis among people with high hemoglobin glycation, or “high glycators,” and underdiagnosis of “low glycators.”

The ADA's decision to endorse the HbA_1c as a diagnostic tool is “overall, not to my mind satisfactory,” said Dr. Bloomgarden, editor of the Journal of Diabetes.

But Dr. Mayer Davidson, who was part of the expert panel that endorsed HbA_1c for diagnosing diabetes last summer, is on the opposite end of the spectrum. He said the recommendation to use HbA_1c for diabetes diagnosis is long overdue.

“Unfortunately, the ADA kept the glucose criteria, which will lead to the confusing situation of people who have diabetes by one criterion but not by the other when both are measured, which is likely to occur frequently,” said Dr. Davidson, professor of medicine, Charles Drew University and David Geffen School of Medicine at the University of California, Los Angeles.

Based on the expert committee's deliberations, it's likely that the ADA and the other organizations will ultimately transition to use of HbA_1c alone for diagnosis, but it may take time. Until then, he advised that physicians who want to use repeat testing for diagnosis stick to the same test both times to avoid confusion. Bottom line: “One should not intermingle the glucose and A_1c criteria.”

The ADA document says that using the same test is “preferred” but provides specific guidance for both testing scenarios.

Along with the 6.5% cutoff for diabetes diagnosis, the ADA now categorizes patients with HbA_1c levels of 5.7%–6.4% under the new heading “Categories of Increased Risk for Diabetes,” replacing “Diagnosis of Pre-Diabetes.”

The 5.7% threshold was derived from unpublished data suggesting that it has the best combination of sensitivity (39%) and specificity (91%) to identify cases of impaired fasting glucose. Other analyses suggest that an HbA_1c of 5.7% is associated with a diabetes risk similar to that of the high-risk participants in the landmark Diabetes Prevention Program trial.