A single blood sample to test both fasting glucose and hemoglobin A1c (HbA1c) may be sufficient to identify people with undiagnosed type 2 diabetes, according to a study published June 19 in the Annals of Internal Medicine.
American Diabetes Association guidelines state that a second test at a later date is preferred to confirm a diagnosis but “two different biochemical tests exceeding diagnostic thresholds” may also work, according to lead author Elizabeth Selvin, PhD, MPH, and colleagues. However, before this study, it was unclear whether two tests commonly taken together—blood glucose and hemoglobin A1c—could provide this confirmation.
Selvin et al. studied 12,268 people from the Atherosclerosis Risk in Communities (ARIC) cohort who didn’t have a diagnosis of diabetes at baseline. Upon testing, 978 of them had either elevated glucose or A1c levels, and 39 percent of those individuals had elevated values on both tests.
The latter group—with two “positive” tests for diabetes markers—was considered to have confirmed undiagnosed diabetes. People with only one elevated test were classified as having unconfirmed undiagnosed diabetes.
After 15 years of follow-up, the researchers found 88.7 percent of those with confirmed undiagnosed diabetes went on to receive a formal diagnosis. In contrast, 71.1 percent of patients with only one elevated marker received a formal diagnosis within 15 years.
Both sets of patients went on to have a higher incidence of cardiovascular and kidney disease than the rest of the study cohort, but the associations were particularly strong in those with high amounts of both glucose and A1c.
“Current clinical practice guidelines are not clear on whether HbA1c and fasting glucose levels from a single blood sample can be used to diagnose diabetes,” Selvin et al. wrote. “Our findings support clinical use of a combination of HbA1c and fasting glucose levels from a single blood sample to identify cases of undiagnosed diabetes in the population, although these results will need to be confirmed in other data sets.”
Elevated levels of either measure were significantly associated with a future diagnosis of diabetes, but HbA1c (hazard ratio: 6.40) was more predictive than fasting glucose (HR: 5.56).
Confirmed undiagnosed diabetes carried a 3.5-fold risk of peripheral artery disease over follow-up and a 25-fold increase in the risk of being formally diagnosed with diabetes. Unconfirmed undiagnosed diabetes, on the other hand, was associated with 5.75-fold odds of an eventual diabetes diagnosis.
“Progression to diagnosed diabetes was high in persons with elevated glucose or HbA1c level (confirmed or unconfirmed), although the absolute and relative risks for the confirmed definition were extraordinarily high—nearly all participants with confirmed undiagnosed diabetes who remained alive were subsequently diagnosed with diabetes,” the authors wrote. “This is not to say that persons with unconfirmed undiagnosed diabetes were not at risk for clinical outcomes; by definition, this population has a high prevalence of prediabetes, and our data demonstrate that they are at future risk for diabetes and other major clinical outcomes.”
The conclusion of this study could be particularly useful in large epidemiological studies, the authors noted, because requiring only one blood sample would be significantly more cost-effective than requiring research participants to return for a second visit.
In a related editorial, two researchers from Emory University in Atlanta highlighted the impressive specificity of the one-sample test—98.1 percent to identify patients diagnosed with diabetes at five years, increasing to 99.6 percent at 15 years. However, the method’s sensitivity was only 54.9 percent at five years.
“The criteria proposed by Selvin and colleagues may miss a large number of persons with diabetes,” wrote K.M. Venkat Narayan, MD, MSc, MBA, and Ram Jagannathan, PhD. “This tradeoff between sensitivity and specificity is important because the evidence now favors early intervention for persons with undiagnosed diabetes and even prediabetes.”
Even so, the one-sample test has the potential to more efficiently identify patients at risk of diabetes and related health problems—a significant finding considering diabetes care cost $327 billion in 2017 in the U.S. alone.
“Early detection and diagnosis of diabetes are critical for appropriate initiation of interventions to prevent or delay complications,” the editorialists wrote. “Selvin and colleagues offer an innovative and practical use of a single blood sample at one visit, rather than two samples obtained at two visits, to confirm the diagnosis of diabetes. This approach has appeal, especially for resource-challenged settings, but it needs replication in other populations before becoming accepted clinical practice.”