TAKE-HOME POINTS
■ A1C values may replace previous thresholds for diagnosing diabetes, except in cases that make the A1C assay impossible, impractical, excessively expensive, or inaccurate.
■ The threshold of an A1C value of 6.5% or higher is the recommended cut-point for a diagnosis of diabetes.
■ Persons with an A1C value higher than 6% should be offered lifestyle interventions, which will vary based on available community resources, size of the target population, and nature of the intervention.
An international expert committee recommends using the glycosylated hemoglobin (A1C) assay as the new standard diagnostic test for diabetes. The committee reports that A1C measurement of chronic glycemic levels provides a better diagnosis than the currently used tests.1
For the first time, attention was focused on the relationship between glucose levels and the presence of long-term complications. In the past, the National Diabetes Data Group relied on distributions of glucose levels, rather than the relationship between glucose level and diabetes-related complications, to diagnose the disease. The A1C assay may replace the standard fasting plasma glucose (FPG) test and the oral glucose tolerance test (OGTT). The committee also negated the previously held belief that the 2-hour plasma glucose test is the gold-standard for diagnosing diabetes.
The recommendations set an A1C value of 6.5% or higher as diagnostic. This value appears to be the level at which a person is at risk for developing the complications of diabetes. A diagnosis should be confirmed with a repeat A1C test, unless clinical symptoms and a glucose level higher than 200 mg/dL are present.
Many primary care providers already use the A1C assay as a first-line screen for diagnosis, said Richard Kahn, PhD, Chief Scientific and Medical Officer of the American Diabetes Association, who moderated the press conference at which the recommendations were reported.2 Other clinicians use A1C in combination with FPG. One reason for the caution, some say, has been a lack of standardization of the A1C assay. Indeed, previous expert committees expressed concern over the lack of assay standardization. A 2003 follow-up report noted that great strides were made in standardizing most of the assays used in the United States.1
In addition, glucose measurement is less accurate and less precise than most clinicians realize. A recent analysis of the performance of a variety of clinical laboratory instruments and methods for measuring glucose revealed that 41% of glucometers have significant bias from the reference method, potentially resulting in the misclassification of more than 12% of patients.1
ADVANTAGES OF A1C
Proponents say the A1C assay has several major advantages over other diagnostic tests. First, unlike the FPG test or the OGTT, the A1C assay measures the average glucose level during the preceding 2 to 3 months, rather than at just that point in time. Measurements that capture long-term glycemic exposure may serve as a better biochemical marker of diabetes. Compared with single measures of glucose concentration, the A1C value should provide a better indicator of the presence and severity of the disease. Observational studies have consistently demonstrated a strong correlation between retinopathy and A1C level, but a less consistent relationship has been seen between retinopathy and FPG levels. The correlation between A1C level and diabetes-related complications is also proven in controlled clinical trials and has been used to establish treatment goals.
Second, A1C levels are relatively stable after collection. The recent introduction of a new reference method for calibrating A1C assay instruments should further improve assay standardization in most of the world.
Third, between- and within-patient variability is substantially lower in A1C assay results than in glucose measurements. The A1C value has a day-to-day within-person variance of less than 2%, whereas FPG test results have a 12% to 15% variance.
Fourth, the ease and convenience of sample collection is superior because samples for A1C assay do not require patient preparation; on the other hand, the FPG test requires a timed sample after an 8-hour fast. Finally, A1C samples are stable at room temperature; glucose measurements from FPG samples, however, may decrease after as little as 1 to 4 hours at room temperature.1