Nav: Home

Genetic marker linked to increased risk of diabetic peripheral neuropathy

June 11, 2019

BOSTON - (June 11, 2019) - Researchers from Joslin Diabetes Center, using a genome-wide association study, have identified a genetic factor linked to the development of diabetic peripheral neuropathy. This finding suggests a new target for preventive therapies. The research has been published online and will appear in the August print issue of Diabetes.

While neuropathy, which causes pain or numbness in the legs and an increase risk of foot ulcers, is a major problem for many people with diabetes, there is significant variability in its onset: some people develop this complication, and others do not, says Alessandro Doria, MD, PhD, MPH, a study senior author and Director of the Molecular Phenotyping and Genotyping at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School in Boston. "Therefore, we wanted to see if we could discover genetic factors that predispose people with diabetes to developing this complication versus being protected from it."

For this study, researchers used an approach called a genome-wide association study, or GWAS. This analysis is used to find disease-associated variants throughout the genome. A GWAS for diabetic peripheral neuropathy was carried out in 5,168 participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial --- 4,384 with evidence of peripheral neuropathy and 784 who were spared this complication.

After screening millions of small variations of the genome sequence (genetic variants), the study identified a region on chromosome 2q24 as having a powerful impact on the risk of peripheral neuropathy in type 2 diabetes. While the precise mechanisms are not known, there were some hints that the genetic variants in this region may act by affecting a nearby sodium channel regulating the transmission of sensory signals in peripheral nerves.

"People carrying the less frequent variant at that location were protected from neuropathy and people carrying the more common variant at that same location were predisposed to this complication," says Doria.

The implication is that this could be a target for pharmacological therapy to protect people from diabetic peripheral neuropathy. "We found that people with the protective allele have higher amounts of this sodium channel," says Doria. "This suggests that the sodium channel in the peripheral nerves might be used to protect people from neuropathy, by developing a drug that activates this channel."

This finding was replicated in an independent study, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

"The study is important because it's the first real effort to have a genome wide search for genes predisposing to this complication of diabetes. Diabetic peripheral neuropathy is often overlooked," says Hetal Shah, MD, MPH - a study senior author and a Research Associate at the Joslin Diabetes Center and Instructor of Medicine at Harvard Medical School. "Yet nearly one-fourth of the annual US expenditure on diabetes is due to diabetic peripheral neuropathy."

One limitation of this study is that it included only white subjects, so it's not known whether these findings also apply to people of other races.
-end-
Other study participants include Yaling Tang, MD, Petra A. Lenzini, MS, Rodica Pop Busui, MD, PhD, Pradipta R. Ray, PhD, Hannah Campbell, MPH, Bruce A. Perkins, MD, MPH., Brian Callaghan, MD, MS, Michael J. Wagner, PhD, Alison A. Motsinger-Reif, PhD, John B. Buse, MD, PhD, Theodore J. Price, PhD, Josyf C. Mychaleckyj, DPhil., Sharon Cresci, MD.

This study was supported with grants from the National Institutes of Health (NIH).

About Joslin Diabetes Center

Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is an independent, non-profit institution affiliated with Harvard Medical School, and one of only 11 NIH-designated Diabetes Research Centers in the U.S.

For more information, visit http://www.joslin.org or follow @joslindiabetes | One Joslin Place, Boston, MA 617-309-2400

Joslin Diabetes Center

Related Diabetes Articles:

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
More Diabetes News and Diabetes Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...