Genetics linked to body shape could lead to increased risk of diabetes

A new study suggests people who are less likely to store fat around their hips also face a higher likelihood of suffering a heart attack.

Gene variations which reduce ability to store fat around the hips have been linked to higher risk of diabetes and heart attacks.

People who are less likely to put on excess fat around their hips due to their genes are at an increased risk of Type 2 diabetes and heart attacks, according to a new study.

While it has long been recognised that an “apple-shaped” body is associated with an increased risk of diabetes and heart disease, scientists said the new research sheds light on the specific genetics linked to this body shape and the potential mechanisms behind the increased risk.

The team, from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, suggest their findings may help to better identify individuals at risk of developing these conditions and inform their subsequent treatment.

Researchers studied the genetic profiles of more than 600,000 participants from several large UK and international studies.

They identified more than 200 genetic variants that predispose people to a higher waist-to-hip ratio, a measure of the “apple-shaped” body.

Using this data, they identified two specific groups of genetic variants that increased waist-to-hip ratio – one exclusively via lower hip fat and the other exclusively via higher waist (abdominal) fat.

Senior author Dr Claudia Langenberg, programme leader at the MRC Epidemiology Unit, said: “We found that both of the genetic variants we identified were associated with higher risk of Type 2 diabetes and heart attacks.

“The concept of an ‘apple-shaped’ figure has been understood for some time but our research considers how this body shape alters fat distribution in the body.

“Genetics which specifically change fat distribution by lowering fat storage around the hips increase risk of disease independent of, and in addition to, mechanisms that affect abdominal fat storage.”

The study, which is published in JAMA, saw the team conduct detailed assessments of fat distribution in different regions of the body of 18,000 people using DEXA, a low-intensity X-ray scan that can distinguish body fat, bone composition, muscle and lean mass across the whole body.

Lead author Dr Luca Lotta, senior clinical investigator at the MRC Epidemiology Unit, said: “It may seem counter-intuitive to think that some people with less fat around their hips are at higher risk of diabetes or heart disease.

“We believe that this is due to a genetically-determined inability to store excess calories safely in the hip region as opposed to elsewhere.

“This means that individuals with this genetic make-up preferentially store their excess fat in the liver, muscles or pancreas, or in their blood in the form of circulating fats and sugar, any of which can lead to a higher disease risk.

“We are trying to understand whether some of the genes identified by our study may be suitable targets for future drug development but this process may take several years.”

The team said they hope their findings will help to better understand the ways in which fat storage in different body compartments affects metabolic health and leads to disease and suggested their work could refine the way we detect and treat people at risk.

Dr Langenberg added: “Not all apple shapes are the same.

“Guidelines that focus solely on measuring waist circumference to assess risk overlook people whose body shape is not adequately captured by this metric but who are still likely to develop cardiovascular and metabolic diseases.

“Carrying excess weight around the hips is a metabolically safer way of storing fat but those who aren’t genetically predisposed to doing so would benefit greatly from lifestyle interventions, such as restricting their calorie intake or increasing their physical activity.”

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