According to a report published in the magazine Nature Medicinea common genetic variation in people of African descent is associated with an increased risk of complications diabetesincluding diabetic retinopathy.
Genetic variations in diabetes
Researchers have found that diabetes diagnosis and treatment needed to prevent diabetes complications may be delayed in people who carry the G6PDdef variant, because it is associated with reduced levels of HbA1c, a widely used clinical indicator of blood glucose levels.
Testing for the genetic variations that cause G6PD deficiency could lead to improvements in how doctors diagnose and treat diabetes, thereby helping to reduce the long-seen disparity in diabetes complications between individuals of European and African descent, he concludes I study.
The multi-institutional study was conducted by Vanderbilt University Medical Center (VUMC), the VA Tennessee Valley Healthcare System and the U.S. Department of Veterans Affairs’ Million Veteran Program (MVP), Emory University School of Medicine, and Joseph Maxwell Cleland Atlanta VA Health System.
“This discovery could lead to changes in how diabetes is managed for millions of patients in the United States and around the world,” said Todd Edwards, Ph.D., MS, co-corresponding author of the study with Ayush Giri, Ph.D. . Both are VUMC faculty members affiliated with the VA Tennessee Valley Healthcare System.
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“More needs to be done, such as health economics and policy studies and clinical trials, to determine how best to use this knowledge to prevent diabetes complications,” said Edwards, associate professor of Medicine. “Now the trial can begin.”
More than 400 million people worldwide suffer from G6PD deficiency. While most MVP participants are men, millions of women are also at increased risk of diabetes complications if they carry one copy of the G6PDdef variant.
“While this finding may impact how millions of individuals manage diabetes, it also highlights the importance of including diverse populations in biomedical research,” said the study’s first author, Joseph Breeyear, Ph.D., M.S. , postdoctoral researcher at UCLA. National Institute of Environmental Health Sciences of the National Institutes of Health (NIH).
“By including underrepresented individuals, we can identify genetic variations that influence health outcomes,” said Breeyear, who earned his Ph.D. in Human Genetics in the Edwards laboratory at VUMC in 2023.
Diabetic retinopathy, damage to the retinal blood vessels and nerves at the back of the eye that can cause permanent vision loss, has previously been linked to genetic variations called single nucleotide polymorphisms, or SNPs, but these associations have been studied primarily in Individuals of European ancestry and 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 but others do not, researchers conducted a combined-ancestry genome-wide association study (GWAS) of more than 197,000 individuals with diabetes, including more than 68,000 who also had diabetic retinopathy.
The study represented the largest ancestry-stratified, SNP-based estimate of the heritability of diabetic retinopathy conducted to date and included an unprecedented number of individuals of non-Hispanic African descent: more than 46,000.
The researchers used electronic health records and genomic data from the Million Veteran Program, the UK Biobank, VUMC’s biorepository, called BioVU, the Mass General Brigham Biobank in Boston, and summary statistics from a 2019 study.
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They also studied the effect of G6PDdef on the risk of diabetes complications among participants in the NIH-sponsored Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial, which evaluated the impact of tight diabetes control on events cardiovascular diseases in more than 10,000 adults with type 2 diabetes.
Their analysis found that individuals of non-Hispanic African descent with G6PDdef in the ACCORD study were significantly more likely to develop two diabetes complications – diabetic retinopathy and diabetic nephropathy – than individuals without the variant, despite receiving standard treatment of treatment to lower HbA1c levels.
The current study found nine previously unreported loci, or locations on chromosomes, that were associated with diabetic retinopathy, including an evolutionarily adaptive genetic variant that could potentially explain some of the racial disparity in diabetes complications.
The G6PDdef variant causes a deficiency of the enzyme glucose 6-phosphate dehydrogenase. Common only in African and some Asian populations, this genetic variation may have evolved as protection against severe malaria.
It is associated with a shorter lifespan of red blood cells, which lowers HbA1c levels but not blood glucose levels. This “discrepancy” can mask the true extent of hyperglycemia: in individuals carrying the G6PDdef mutation, HbA1c levels systematically underestimate blood glucose levels.
Based on the prevalence of this genetic variant, researchers estimated that more than 250,000 men and 500,000 women of non-Hispanic African descent in the United States with diabetes may have some level of G6PD deficiency.
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These figures are broadly consistent with an earlier study, which estimated that diabetes may be diagnosed late, or remain undiagnosed, in as many as 650,000 people of non-Hispanic African descent in the United States due to the G6PDdef variant.
“With comprehensive screening… and subsequent standard treatment, possibly targeting glucose-related goals rather than HbA1c, nearly 12% of diabetic retinopathy cases and 9% of diabetic neuropathy cases in individuals of non-Hispanic African descent could be avoided in the United States alone,” the researchers concluded.
HbA1c works well as a marker of hyperglycemia in most people, but not as well in individuals with genetic disorders that affect enzyme function such as G6PD deficiency, noted Giri, assistant professor of Obstetrics and Gynecology at VUMC.
“If HbA1c wasn’t widely used for diabetes screening and management, we probably wouldn’t be seeing this outcome,” he said.
Eighteen research teams, including six affiliated with the VA, contributed to the study.
Importance of routine eye care for patients with diabetes
Diabetes is a widespread condition worldwide, affecting approximately 10% of the population. It is a condition that occurs due to a problem in the way the body regulates and uses sugar as fuel. It is a systemic disease that affects many organs, including the heart, blood vessels, nerves, kidneys and eyes.
While eye care and regular eye exams are important for everyone, they are especially vital for people with diabetes. Let’s explore why routine eye care is so important.
The eye, a vital part of your vision, contains a sensitive layer called the retina. The blood vessels in the retina can be affected by diabetes, leading to a condition known as diabetic retinopathy. This condition gradually damages these blood vessels and can progress through various stages of severity.
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When diabetic retinopathy develops, eye damage may occur before symptoms develop. Often, no symptoms appear until the retinopathy reaches a moderate or advanced stage. In the advanced stage, diabetic retinopathy can cause rapid and permanent vision loss.
Diabetic retinopathy is the leading cause of vision loss worldwide in people aged 25 to 74. By 2030, an estimated 191 million people worldwide will have diabetic retinopathy and 56.3 million people with diabetes will have sight-threatening diabetic retinopathy.
For people with diabetes, regular eye screening is part of the annual exam performed by your primary care doctor.
The Food and Drug Administration (FDA) has approved the first autonomous artificial intelligence (AI) system that helps detect diabetic retinopathy. The system takes an ocular photograph of the eye’s retina to identify early signs of vascular damage. Eyepiece photography is quick and designed for your comfort during the process.
If screening detects diabetic retinopathy, your healthcare team will refer you to retina specialists or an ophthalmology specialist for further evaluation and management of the condition.
Prevention remains the best approach for diabetic retinopathy. Early diagnosis and diligent management by an ophthalmologist can slow the progression or halt diabetic retinopathy. A timely diagnosis increases the chances of a favorable outcome.
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Even if your annual eye exam shows no problems, it is critical to report any of these symptoms to your healthcare team immediately:
•Blurred vision
•Double vision
•Dark or empty spot in the center of your vision
•Reading difficulty
•Difficulty seeing well at night
•Dropping eyelid
•Eye pain
•Flashing lights
•Halos around lights
•Objects that seem larger or smaller than usual
•Sudden appearance of spots or floaters
•These symptoms may indicate that you need to change your eyeglass or contact lens prescription or signal other more serious conditions, such as diabetes-related eye complications such as diabetic retinopathy.
Strict control of blood glucose levels reduces the risk of developing vision loss due to diabetic retinopathy. Additionally, you should check your high blood pressure and cholesterol, as they can affect the health of the retina of your eyes.
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