The introduction of hemoglobin A1c as an option for diagnosing type 2 diabetes over a decade ago may have resulted in underdiagnosis, new research indicates.
In 2011, the World Health Organization advised that A1c measurement, with a cutoff value of 6.5%, could be used to diagnose diabetes. The American Diabetes Association had issued similar guidance in 2010.
Prior to that time, the less-convenient 2-hour oral glucose tolerance test (OGTT) and fasting blood glucose (FBG) were the only recommended tests. While WHO made no recommendations for interpreting values below 6.5%, the ADA designated 5.7%-6.4% as prediabetes.
The new study, published online in The Lancet Regional Health–Europe, showed that the incidence of type 2 diabetes in Denmark had been increasing prior to the 2012 adoption of A1c as a diagnostic option but declined thereafter. And all-cause mortality among people with type 2 diabetes, which had been dropping, began to increase after that time.
“Our findings suggest that fewer patients have been diagnosed with [type 2 diabetes] since A1c testing was introduced as a convenient diagnostic option. We may thus be missing a group with borderline increased A1c values that is still at high metabolic and cardiovascular risk,” Jakob S. Knudsen, MD, of the department of clinical epidemiology, Aarhus (Denmark) University Hospital, and colleagues wrote.
Therefore, Dr. Knudsen said in an interview, clinicians should “consider testing with FBG or OGTT when presented with borderline A1c values.”
The reason for the increase in mortality after incident type 2 diabetes diagnosis, he said, “is that the patients who would have reduced the average mortality are no longer diagnosed...This does not reflect that we are treating already diagnosed patients any worse, rather some patients are not diagnosed.”
But M. Sue Kirkman, MD, emeritus professor of medicine at the University of North Carolina at Chapel Hill, who was part of the writing group for the 2010 ADA guidelines, isn’t convinced.
“This is an interesting paper, but it is a bit hard to believe that a change in WHO recommendations would have such a large and almost immediate impact on incidence and mortality. It seems likely that ... factors [other] than just the changes in recommendations for the diagnostic test account for these findings,” she said.
Dr. Kirkman pointed to new data just out from the Centers for Disease Control and Prevention on Jan. 26 that don›t show evidence of a higher proportion of people in the United States who have undiagnosed diabetes, “which would be expected if more cases were being ‘missed’ by A1c.”
She added that the CDC incidence data “show a continuing steady rate of decline in incidence that began in 2008, before any organizations recommended using A1c to screen for or diagnose diabetes.” Moreover, “there is evidence that type 2 diabetes incidence has fallen or plateaued in many countries since 2006, well before the WHO recommendation, with most of the studies from developed countries.”
But Dr. Knudsen also cited other data, including a study that showed a drop or stabilization in diagnosed diabetes incidence in high-income countries since 2010.
“That study concluded that the reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources, which was a main objective of our study,” wrote Dr. Knudsen and coauthors.
Dr. Knudsen said in an interview: “We are not the first to make the point that this sudden change is related to A1c introduction...but we are the first to have the data to clearly show that is the case.”