Sickle Cell Gene Variant Lowers A1C Readings
An analysis of two major public health studies involving more than 4,600 people indicated that HbA1c readings were substantially lower in people with sickle cell trait (SCT) than in those without SCT.
Affecting 8 to 10 percent of African Americans, SCT is a genetic hemoglobin variant found in individuals who carry one copy of the variant. Carrying two copies leads to sickle cell disease.
The HbA1c analysis suggests physicians relying on this test may miss opportunities to diagnose and treat some people with pre, or type 2 diabetes. “We found the HbA1c was systematically lower in African-Americans with sickle cell trait than those without sickle cell trait despite similar blood sugar measurements using other tests,” said lead study author Mary Lacy, a doctoral candidate at Brown University School of Public Health.
Using standard HbA1c cutoffs, the study team discovered 40 percent fewer potential pre-diabetes cases, and 48 percent fewer potential diabetes cases were identified in people with SCT. However, using fasting and two-hour blood glucose tests, no appreciable difference in the detection of potential diabetes was found between SCT, and non-SCT individuals.
“For patients with diabetes, HbA1c is often used as a marker of how well they are managing their diabetes, so having an underestimation of their blood sugars is problematic because they might have a false sense of security, thinking they are doing okay when they are not,” said study author and cardiologist Wen-Chih Wu, Providence Veterans Affairs Medical Center, and associate professor at Brown University.
The strength of the HbA1c analysis is its large sample size that involved two studies with diverse populations. The investigation was also statistically controlled for demographic and medical factors such as age, gender, BMI, and diagnostic history.
Though the analysis does not explain why HbA1c readings are low with SCT, researchers suggest the hemoglobin variant might give some red blood cells decreased lifespans, so the hemoglobin would accumulate less blood glucose and give a low HbA1c reading.
“Irrespective of the reason...the underestimation is very real, and clinicians should consider screening for sickle cell trait and account for the difference in HbA1c,” said Wu.