Where your body stores fat affects diabetes risk

by Barbara Hewitt on January 7, 2019

People who are less likely to put on excess fat around their hips due to their genes are at higher 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, the new research sheds light on the specific genetics linked to this body shape and the potential mechanisms behind the increased risk.

Body Types

Image by By M-SUR/Shutterstock.com

The study, led by scientists from the MRC Epidemiology Unit at the University of Cambridge in England, aims to help to better identify individuals at risk of developing these conditions and inform their subsequent treatment.

The researchers studied the genetic profiles of over 600,000 participants from several large UK and international studies and identified over 200 genetic variants that predispose people to a higher waist to hip ratio, a measure of the apple shaped body.

Using this data, the researchers 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.

‘We found that both of the genetic variants we identified were associated with higher risk of type 2 diabetes and heart attacks,’ said senior study author, Dr Claudia Langenberg, programme leader at the MRC Epidemiology Unit.

‘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,’ she explained.

According to lead author, Dr Luca Lotta, senior clinical investigator at the MRC Epidemiology Unit, it may seem counterintuitive 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,’ she said.

To validate their findings, the authors conducted 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.

The researchers also suggest that there is a greater proportion of people in the general population with subtle forms of familial partial lipodystrophy, a rare genetic disorder characterised by the inability to develop fat in the arms, legs and buttocks. Those with this condition often go on to develop diabetes and its cardiovascular complications.

The team behind the research hope that their findings will help to better understand the ways in which fat storage in different body compartments affects metabolic health and leads to disease. They suggest their work could refine the way people are risk are detected and treated.

Dr Langenberg pointed out that 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,’ she said.

‘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,’ she added.

Existing diabetes drugs called glitazones prevent or improve the disease in part by enhancing the ability to expand hip body fat. However, their use in clinical practice is limited by some of their side-effects.

Dr Lotta said that the researchers hope that their genetic findings might lead to the development of new agents targeting body fat deposition in the future.

‘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,’ she added.

The opinions expressed in this article do not necessarily reflect the views of the DiabetesForum.com Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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