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Glycated haemoglobin potential alternative to fasting glucose in diabetes screening

Tristan Manalac
31 Oct 2018

Glycated haemoglobin (HbA1c) is as effective as fasting plasma glucose (FPG) in screening for and diagnosing diabetes, said Dr Wei-Yen Lim, of the Department of Clinical Epidemiology of the Tan Tock Seng Hospital, at the recently concluded Singapore Health and Biomedical Congress (SHBC) 2018.

“Our current screening guidelines recommend universal screening for everyone 40 years and older using fasting venous glucose,” he added. “However, there are well-known disadvantages to the current screening regime. This includes the need to fast.”

Lim and his group thus examined the potential of using HbA1c, a useful proxy for the measurement of glucose in the bloodstream, as a potential screening tool for diabetes in 3,540 participants who were not known diabetics (52.4 percent female) and who underwent both the oral glucose tolerance test (OGTT) and HbA1c testing.

Of the study cohort, 7.6 percent (n=332) had test results that were in the diabetic range. Using receiver-operator characteristic curve analysis, researchers showed that there was no significant difference in the discriminative capabilities of FPG and HbA1c in detecting diabetes (area under the curve: 0.9323 vs 0.9216; p>0.05).

The same remained true even when the participants were stratified according to ethnicity: Malays (0.9465 vs 0.9344), Chinese (0.9103 vs 0.8698) and Indians (0.9385 vs 0.953; p>0.05 for all).

Moreover, at FPG cut-off 6.1 mmol/L, sensitivity and specificity for identifying diabetes were 0.692 and 0.963, respectively. HbA1c achieved similar values when a cut-off of 6.3 percent was used.

“While HbA1c at 6.3 percent gives similar sensitivity and specificity to fasting glucose at 6.1 mmol/L, we would argue that we should lower this threshold to 6.1 percent to improve the sensitivity,” said Lim. He pointed out that at this lower threshold, HbA1c would be able to identify 13.3-percent more diabetics (69.2 percent vs 82.5 percent) and 12.9-percent more individuals with impaired glucose tolerance (32.5 percent vs 19.6 percent) than FPG 6.1 mmol/L.

These additional benefits would come with a trade-off of 4.5-percent more individuals wrongly identified as diabetics. However, this consequence is unlikely to outweigh the advantages of lowering the HbA1c threshold, he argued.

Given that “the intervention that we plan for this group of individuals is lifestyle modification and intensive follow-up, we would argue that actually these false positives will not necessarily suffer much adverse harms,” Lim added.

In the clinical setting, he and his team recommend that, following an initial screen using HbA1c, a confirmatory test using FPG should employ a lower threshold of 5.6 mmol/L. This will lead to the identification of 15.5-percent more diabetics and 10.8-percent more patients with IGT. This will also increase the number of false positives by 1.4 percent, but to limited significant consequences.

“While several countries have recommended the use of HbA1c for screening, a universally accepted cut-off has not been described; Singapore currently does not recommend the use of HbA1c in screening or diagnosis. However, it holds promise in being able to improve screening uptake, and it might be able to identify more individuals with diabetes than the use of fasting glucose,” said Lim.

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