An international team of researchers has found that a genetic variant carried almost exclusively by African Americans significantly reduces the accuracy of the standard test for type 2 diabetes, the glycated haemoglobin or HbA1c test. The test measures the amount of glucose that is carried by the red blood cells over the previous two to three months.

At least one copy of the variant in the G6PD gene is carried by around 11 per cent of African Americans. This means around 650,000 African Americans in the US could have undiagnosed type 2 diabetes if tested with the HbA1c test alone.

The results, published in PLOS Medicine, suggest screening for G6PD alongside the diagnostic test, or using other diagnostic tests in populations with African ancestry in order to improve diagnoses of type 2 diabetes.

In the largest study of its kind, an international team of more than 200 scientists investigated genetic variants which are thought to affect the HbA1c test.

The team studied genetic variants in almost 160,000 people from European, African, East Asian and South Asian ancestries, who were not known to have type 2 diabetes. Researchers discovered 60 genetic variants that influence the outcome of HbA1c tests, of which 42 variants were new.

The G6PD gene was found to significantly impact the results of the HbA1c test. “The issue with the G6PD genetic variant is it artificially lowers the value of blood sugar in the HbA1c test, and can lead to under-diagnosis of people with type 2 diabetes,” said Inês Barroso, joint lead author from the Wellcome Trust Sanger Institute in Cambridge, UK.

“The G6PD genetic variant shortens the three-month lifecycle of red blood cells. So in African Americans who have this variant, their red blood cells don’t live long enough to bind to the glucose in the blood. Therefore these people will have a lower level of HbA1c, which won’t show as a positive result for type 2 diabetes,” said Eleanor Wheeler, joint first author from the Sanger Institute.

Impact of common genetic determinants of Haemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. PLOS Medicine. DOI: 10.1371/journal.pmed.1002383