STORED FAT AROUND THE WAIST MAY NOT INCREASE DIABETES RISKS FOR EVERYONE.

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STORED FAT AROUND THE WAIST MAY NOT INCREASE DIABETES RISKS FOR EVERYONE.

For some people, gene variants may cause abdominal fat storage while protecting them from diabetes.



Conventional wisdom holds that storing fat around your belly increases your risk for type 2 diabetes. But surprising new findings from the University of Virginia School of Medicine suggest that naturally occurring gene variations can lead some people to store fat at the waist and protect them from diabetes.

The unexpected discovery provides a more nuanced view of the role of obesity in diabetes and related health conditions. It also could pave the way for more personalized medicine -- treatments tailored to the individual. For example, the researchers say doctors might prioritize weight loss for patients whose genes put them at increased risk but place less emphasis on it for patients with protective gene variants.

"There is a growing body of evidence for metabolically healthy obesity. In this condition, people who would normally be at risk for cardiovascular diseases and diabetes because they are obese are actually protected from adverse effects of their obesity. In our study, we found a genetic link that may explain how this occurs in certain individuals," said researcher Mete Civelek, Ph.D., of UVA's Center for Public Health Genomics. "Understanding various forms of obesity is important to tailor treatments for individuals at high risk for adverse effects of obesity."

As medicine grows more sophisticated, understanding the role of naturally occurring gene variations will be important in ensuring patients get the best, most tailored treatments. The new work by Civelek and his team, for example, indicates that variants can simultaneously predispose some people to store fat at the abdomen -- thought to put them at increased risk for a cluster of health problems called metabolic syndrome -- while protecting them from type 2 diabetes. (Metabolic syndrome raises the risk for diabetes, stroke, and other serious health issues.)

One of the metrics doctors use to determine if a patient has metabolic syndrome is abdominal obesity. This is often calculated by comparing the patient's waist and hip measurements. But Civelek's research suggests that, for at least some patients, it may be more complex. In the future, doctors may want to check a patient's genes to determine how to best guide the person to good health.

"We found that among the hundreds of regions in our genomes which increase our propensity to accumulate excess fat in our abdomens, there are five which have an unexpected role," said Jonathan Aberra, the lead author of the study and a Ph.D. candidate at UVA's Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering. "To our surprise, these five regions decrease an individual's risk for type 2 diabetes."

In addition to producing surprising findings, Civelek's research provides essential new tools for his fellow researchers seeking to understand the complexities of gene variations. The sophisticated approach Civelek and his collaborators developed to identify the relevant variants and their potential effects will be helpful for future research into metabolic syndrome and other conditions.

The scientists say the tools could also prove invaluable in developing new and better treatments for metabolic syndrome.

"We now need to expand our studies in more women and people from different genetic ancestries to identify even more genes that underlie the metabolically health obesity phenomenon," Civelek said. "We plan to build on our findings to perform more experiments to potentially identify a therapeutic target."

The research was supported by the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases, grant R01 DK118287; the National Heart Lung and Blood Institute, award T32 HL007284; the American Diabetes Association, grant 1-19-IBS-105; and the National Science Foundation's Louis Stokes Alliances for Minority Participation Bridge-to-the-Doctorate Virginia-North Carolina Alliance Fellowship.

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