Can HbA1c be used in the screening for diabetes?

I have been asked this question many times by primary care physicians.

The currently accepted criteria for diagnosing diabetes mellitus includes any of the following: fasting plasma glucose ≥126 mg/dL, random plasma glucose ≥200 mg/dL with symptoms of diabetes, or two-hour plasma glucose ≥200 mg/dL during a 75-gram oral glucose tolerance test. The criteria should be repeated on another day to confirm.

HbA1c has not been included in the diagnostic criteria for several reasons. There have been problems with standardization of HbA1C assays. Additional factors, although uncommon, such as hemoglobinopathies, certain medications, hemolysis or iron deficiency may interfere with results. HbA1c is insensitive; it is possible to have diabetes with an HbA1c within the normal laboratory reference range. Finally, there has not been agreement on what exactly the normal range of HbA1c should be.

Saudek and colleagues* proposed that HbA1c be added to the screening and diagnostic criteria for diabetes. They believe that past concerns about standardization should no longer prevent HbA1c from being used as a clinical screening tool. Many patients have diabetes for years before they are diagnosed. Both fasting plasma glucose and the oral glucose tolerance test require a patient to be fasting for at least eight hours whereas the HbA1c does not. If a confounder of HbA1c is present, then the clinician may use the traditional criteria.

According to the authors, if an individual has fasting plasma glucose 100-126 mg/dL, random plasma glucose of 130-199 mg/dL and/or HbA1c of 6% to 6.5%, that is a positive screening test and they should be evaluated further. They consider an HbA1c ≥6.5% consistent with diabetes; however, the diagnosis should be confirmed by the traditional plasma glucose-based criteria.

I have occasionally ordered HbA1c in patients who had evidence of glucose dysmetabolism without diabetes. Even in non-diabetics, higher HbA1c has been associated with greater mortality. If an individual has an HbA1c of 7%, or for that matter >6%, that is not normal. Such information may be useful in identifying which patients may be at future risk to develop diabetes. These individuals can be counseled on therapeutic lifestyle change and followed closely.

On the other hand, a non-elevated HbA1c does not rule out diabetes; I have seen a few patients with HbA1c in the 5.5% to 6% range who nevertheless ruled in with traditional criteria, particularly by oral glucose tolerance testing.

This raises the question: what exactly is a “normal” HbA1c?

It will be interesting to see whether HbA1c is added to the formal screening and diagnostic criteria for diabetes mellitus.

*J Clin Endocrinol Metab. 2008;93:2447-2453.