The hemoglobin A1c test has long been considered the “gold standard” when it comes to diagnosing diabetes. Specifically, an A1c level of 5.7% and higher indicates abnormally high blood glucose levels and corresponds to average blood glucose of 117 mg/dL. An A1c between 5.7% and 6.4% is diagnostic criteria for pre-diabetes, while an A1c of 6.5% and higher is indicative of diabetes.

Strikingly, new research presented today at the ENDO 2019 conference suggests that the A1c test is much more lacking than previously believed when it comes to accurately diagnosing diabetes. In fact, the research showed that the A1c test misclassified over 70% of diabetes cases.

Study Design

Researchers from the City of Hope National Medical Center in California and the University of Kansas Medical Center conducted a study to compare diagnostic specificity and sensitivity of the A1c test as compared to the oral glucose tolerance test (OGTT). While the A1c test represents an estimate of average blood glucose levels over the course of several months, the OGTT shows a real-time blood glucose response to a glucose challenge and thus represents a direct measure of glucose tolerance.

The researchers examined data collected between 2005-2014 from 9,000 adults, excluding those with a pre-existing diabetes diagnosis. They analyzed their body mass index (BMI), fasting plasma glucose (FPG) levels, A1c levels, and 2-hour post-glucose challenge blood sugar levels. They also examined the relevance of race when it came to diagnostic accuracy.

The diagnostic criteria were as follows:

“The states of normal glucose tolerance (NGT), prediabetes, and diabetes mellitus (DM) were based on the criteria as defined by the American Diabetes Association: NGT (FPG<100 mg/dL and 2hPG<140 mg/dL), DM (FPG≥126 mg/dL or 2hPG≥200 mg/dL), prediabetes (FPG 100-125 mg/dL or 2hPG 140-199 mg/dL, but non-diabetic) and A1c (<5.7%; 5.7-6.4%; >6.4%, respectively).”

Major Findings

Remarkably, the research indicates that about 73% of diabetes cases were not picked up by the A1c test, although they were picked up by the OGTT. The research also revealed some race-specific differences in the diagnostic accuracy.

The researchers explain in their study abstract:

“Our results indicated that the prevalence of DM and NGT defined solely by A1c is highly unreliable with a significant tendency for underestimation of the prevalence of DM and overestimation of NGT. Furthermore, race and ethnicity had a significant impact on the sensitivity of A1c criteria. Thus, A1c should not be solely used in determination of prevalence of states of glucose tolerance.”

Dr. Maria Mercedes Chang Villacreses, the lead study author provided further commentary:

“The A1c test showed these people had normal glucose levels when they didn’t. Based on these findings, A1c should not be solely used to rule out diabetes, particularly if a patient has prediabetes or has increased risk factors for developing diabetes. It should be used in conjunction with the oral glucose test for increased accuracy. We want to diagnose diabetes earlier so we can intervene earlier and potentially prevent diabetic complications from developing. The best way to do that is by also using oral glucose tests.”

Conclusions

According to the American Diabetes Association, over 20% of Americans with diabetes are undiagnosed. This is already a staggering statistic, and this breaking research shows that the routine sole use of the A1c test for diagnosis may mean that this number is actually much higher than previously thought.

As diabetes incidence continues to grow, it is ever-important to raise awareness and improve standard protocols for accurate and timely diagnosis as well as to develop the most effective prevention and treatment strategies.

Read more about A1c, American Diabetes Association (ADA), diabetes diagnosis, diabetes research.