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Diabetes: Belly fat gene increases risk

Excess weight is a known risk factor for diabetes. However, the latest study finds that where and how that fat is stored is just as important. The researchers identify and investigate a pivotal fat-controlling gene.
DNA helix illustration
A new study digs into the genetics of fat cells and their relationship with diabetes.

According to the Centers for Disease Control and Prevention (CDC), more than 30 million people in the United States have diabetes. That’s almost 1 in 10 people.

This is no small issue and, as such, a great deal of research effort is spent trying to understand who is most likely to develop the condition, as well as why.

Certain risk factors for type 2 diabetes are already known.

For instance, being 45 or older and having high blood pressure, depression, heart disease, or a family history of diabetes are all likely to raise a person’s risk.

Arguably, the most well-known risk factor is being overweight or obese.

But a new study shows that, although body fat certainly is a risk factor, the story is a little more convoluted.

The research was completed by scientists from the University of Oxford, MRC Harwell, King’s College London — all of which are in the United Kingdom — the University of California, Los Angeles, and the University of Pennsylvania in Philadelphia, among others.

The genetics of fat distribution

Of particular interest to the team was a gene called KLF14.

Although this gene has little impact on a person’s weight, it modifies the way in which fat is stored.

They discovered that in women, a certain variation of KLF14 causes fat to be deposited on the hips rather than the abdomen.

Also, although there are fewer fat cells in total, each one is much larger and chocked full of fat.

The theory is that, because there are fewer fat cells overall, each needs to take on a higher volume of fat and, consequently, it is stored less efficiently.

This results in unhealthful and inefficient fat cells that are likelier to give rise to metabolic disorders, such as diabetes.

Another interesting finding was that the KLF14 gene variant only increases risk in women who inherited the gene from their mother.

In fact, these women had 30 percent greater risk of developing diabetes.

The results — which are published in the journal Nature Genetics — demonstrate that developing type 2 diabetes involves much more than the liver and pancreatic cells that produce insulin; fat cells could play a pivotal role, too.

‘Not all fat is equal’

“Being overweight is known to increase the risk of type 2 diabetes, but this study shows that not all fat is equal: where any excess fat is stored in the body has a big impact on disease risk,” explains co-lead study author Prof. Mark McCarthy, from the University of Oxford.

He continues, “Here, we identify a key gene involved in women in determining whether excess fat is stored around the hips (where it tends to be free of metabolic consequences) or around the waist (where it is particularly likely to increase diabetes risk).”

The authors hope that these new findings will pave the way toward more personalized treatments for type 2 diabetes.

Future studies will be planned to build on these results and develop an understanding of why KLF14 only affects women in this way.

These findings provide one of the most complete understandings of a piece of genetic data — we have studied the KLF14 gene to the point that we understand not only where and how it acts in the body but also who it acts in.”

Co-lead study author Dr. Kerrin Small

Personalized medicine is still in its infancy, but studies such as this bring it closer.

The research also shows how challenging personalized medicine can be.

For example, one gene can have a different impact depending on the sex of the carrier, as well as the sex of the parent from whom they inherited it.

Diabetes:  Belly Fat Gene Increases Risk

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