A newly discovered genetic variation common in people of African ancestry makes the usual blood test for diagnosing diabetes less reliable and helps explain their higher risks for delayed diabetes diagnoses and complications, researchers reported on Tuesday in Nature Medicine.
The variant, called G6PDdef, is associated with a shorter red blood cell lifespan. This results in lower levels of the red blood cell protein hemoglobin A1c commonly used to diagnose diabetes.
People with this variant can have hemoglobin A1c levels well below the thresholds for a diabetes diagnosis and for introduction of increasingly potent treatments – from oral drugs like metformin to injections of insulin – even while their blood sugar levels are high enough to cause diabetes complications such as damage to eyes, nerves, kidneys and other organs, the researchers said.
Testing for genetic variations that cause G6PD deficiency could lead to improvements in the way clinicians diagnose and treat diabetes, thereby helping to reduce the long-observed disparity in diabetes complications between individuals of European and African ancestries, the paper said.
In analyses of genetic data from more than 200,000 individuals with diabetes, the researchers found that glucose levels were significantly higher and HbA1c significantly lower in those with G6PDdef, both in the year preceding a diabetes diagnosis and in the year before a first insulin prescription.
Participants with G6PDdef also had significantly higher risks for diabetic eye disease and nerve damage, despite receiving standard-of-care treatment.
In the U.S. alone, more than 250,000 men and 500,000 women of non-Hispanic African ancestry who have diabetes may have some level of G6PD deficiency, the researchers estimated.
HbA1c works well as a marker for high blood sugar in most people, but not as well in individuals with genetic disorders that affect enzyme function such as G6PD deficiency, Ayush Giri of Vanderbilt University Medical Center in Nashville, one of the study’s senior authors, said in a statement.
“With comprehensive screening… and subsequent standard-of-care treatment, possibly aimed at glucose rather than HbA1c targets, nearly 12% of diabetic retinopathy cases and 9% of diabetic neuropathy cases in individuals of non-Hispanic African ancestry could be avoided in the U.S. alone,” the researchers said.
