A genetic variation common in people of African descent is associated with an increased risk of complications from diabetes, including an eye disease called diabetic retinopathy, according to a report published June 25 in the same journal. . natural medicine.
Researchers found that people carrying the variant G6PDdef are associated with lower HbA1c levels, which is widely used as a clinical marker of blood sugar levels and is therefore necessary for diagnosing diabetes and preventing diabetes complications. It was discovered that treatment may be delayed. Healthcare providers most often use hemoglobin A1Cor HbA1C, a test to measure blood sugar levels and manage diabetes.
Testing for the genetic mutation that causes G6PD deficiency, a deficiency in the enzyme glucose 6-phosphate dehydrogenase, could lead to improvements in how doctors diagnose and treat diabetes. According to the authors, such a test could help reduce long-observed disparities in diabetic complications between people of European and African descent.
“While this discovery has the potential to impact the way millions of individuals manage diabetes, it also highlights the importance of including diverse populations in biomedical research,” said the lead author in the paper. said author Dr. Joseph Breyer, a NIEHS postdoctoral fellow and mentor. Dr. Alison Mottsinger Leaf
“By including underrepresented populations, we can identify genetic variations that influence health outcomes,” said Breyer, who holds a Ph.D. in the field of human genetics in the laboratory of Dr. Todd Edwardsat Vanderbilt University Medical Center (VUMC) in 2023.
More than 400 million people worldwide have G6PD deficiency. Although most of the study participants were men, millions of women are at increased risk of diabetic complications if they carry a copy of the G6PDdef variant.
“This discovery could lead to changes in the way diabetes is managed for millions of patients in the United States and around the world,” said Edwards, co-corresponding author of the paper. Dr. Ayush Giri Both are faculty members affiliated with VUMC. VA Tennessee Valley Healthcare System.
“Much more needs to be done, including health economics, policy research and clinical trials, to establish how best to use this knowledge to prevent diabetes complications,” Edwards said. Ta. “Now the process begins.”
Link to diabetic retinopathy
Diabetic retinopathy, damage to the blood vessels and nerves in the retina at the back of the eye that can cause permanent vision loss, has previously been associated with genetic variations called single nucleotide polymorphisms (SNPs). However, these associations have been primarily studied in Europeans and European populations. Asian ancestry.
The estimated prevalence of diabetic retinopathy in the United States ranges from 24% in non-Hispanic whites to 34% in non-Hispanic blacks.
To better understand why some people with diabetes develop retinopathy while others do not, researchers studied 197,000 patients, including more than 68,000 who had diabetic retinopathy. We conducted a mixed ancestry genome-wide association study (GWAS) on more than 1,000 people with diabetes.
This study is the largest systematic stratified, SNP-based estimate of the heritability of diabetic retinopathy conducted to date, and represents an unprecedented number of non-Hispanic Africans ( (more than 46,000 people) were targeted.
The researchers used electronic medical records and genomic data from the Million Veterans Program, UK Biobank, VUMC's biorepository called BioVU, the Massachusetts General Brigham Biobank in Boston, and summary statistics from the 2019 study. I used it.
They also investigated the effect of G6PDdef on the risk of diabetic complications in participants in the National Institutes of Health-sponsored Actions to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial. This clinical trial evaluated the impact of strict diabetes management on cardiovascular events. 10,000 adults with type 2 diabetes.
Their analysis found that non-Hispanic Africans with G6PDdef in the ACCORD trial were at increased risk of two diabetic complications, diabetic retinopathy and diabetic nephropathy, despite receiving standard treatment due to the mutation. This was found to be significantly higher than those without. HbA1c level.
Mutant may be effective in fighting malaria, but masks high blood sugar
This study detected nine previously unreported genetic loci, or chromosomal locations, associated with diabetic retinopathy. This also includes evolutionarily adapted genetic variations that may explain some of the racial differences in diabetic complications.
The G6PDdef genetic variant is common only in African and some Asian populations and may have evolved as a protection against severe malaria. disease It is caused by a parasite that infects certain types of mosquitoes.
The G6PDdef variant is associated with shortened red blood cell lifespan and reduces HbA1c levels but not blood glucose levels. This “discrepancy” may mask the true extent of hyperglycemia. In individuals with the G6PDdef mutation, HbA1c levels systematically underestimate blood glucose levels.
Based on the prevalence of this genetic variation, researchers believe that more than 250,000 non-Hispanic African men and more than 500,000 women with diabetes in the United States may have some degree of G6PD deficiency. It is assumed that there is a sex.
These numbers exceed previous estimates that as many as 650,000 people of non-Hispanic African descent in the United States may have delayed or undiagnosed diabetes due to the G6PDdef variant. This is almost consistent with research.
“Comprehensive screening followed by standard treatment (presumably glucose-targeted rather than HbA1c-targeted therapy) reduces the incidence of nearly 12% of diabetic retinopathy cases and 9 of diabetic neuropathy cases among non-Hispanic Africans. % could be avoided only in the United States,” the researchers concluded.
HbA1c works well as a marker of hyperglycemia for most people, but not for people with genetic disorders that affect enzyme function, such as G6PD deficiency, says Giri, assistant professor of obstetrics and gynecology at VUMC. he points out.
“If HbA1c had not been widely used for diabetes screening and management, such findings probably would not have been observed,” he said.
(This article is an edited version of the article dated June 25th) VUMC News This article was written by Bill Snyder, Senior Science Writer and Director of Information. )
