Public Release: 

New genetic form of obesity and diabetes discovered

Imperial College London

Scientists have discovered a new inherited form of obesity and type 2 diabetes in humans.

A large number of genes are involved in regulating body weight, and there are now over 30 genes known in which people with harmful changes in DNA sequence become extremely overweight. Similarly, there are a number of genes that can, when altered, cause type 2 diabetes. These conditions are inherited through families in exactly the same way as disorders such as cystic fibrosis or Huntington's disease.

It is unclear what proportion of severe obesity and type 2 diabetes is caused by genetic disease.

Researchers at Imperial College London discovered the new defect by sequencing the DNA of an extremely obese young woman and members of her family. In addition to an increased appetite leading to severe weight problems from childhood, she had type 2 diabetes, learning difficulties, and reproductive problems.

They found that she had inherited two copies of a harmful genetic change that meant she could not make a protein called carboxypeptidase-E (CPE). This is an enzyme that is important in the proper processing of a number of hormones and brain transmitters controlling appetite, insulin and other hormones important in the reproductive system.

Studies have previously shown that CPE deficiency causes obesity, diabetes, and impaired memory in mice, but no humans with the condition have been found before. CPE deficiency is a recessive condition, so a person would need to inherit the altered genetic sequence from both parents to be affected.

The study, published in the journal PLOS ONE, was funded by the NIHR Imperial Biomedical Research Centre and Diabetes UK.

Professor Alex Blakemore from the Department of Medicine at Imperial College London, who led the study, said: "There are now an increasing number of single-gene causes of obesity and diabetes known. We don't know how many more have yet to be discovered, or what proportion of the severely obese people in our population have these diseases - it is not possible to tell just by looking.

"These are serious disorders that affect the body's ability to regulate hunger and fullness signals. They are inherited in the just same way as other genetic diseases and the sufferers should not be stigmatised for their condition. They should be offered genetic counselling and specialised lifelong support to allow them as healthy a life as possible."

The patient was clinically evaluated by consultant endocrinologist Dr Tony Goldstone, who runs a specialist genetics obesity clinic at Hammersmith Hospital. The patient's parents are cousins, giving her a relatively high likelihood of inheriting the same genetic change from both parents. She had an older brother with similar symptoms who died aged 21.

The first author Dr Sanne Alsters, also in the Department of Medicine, who carried out the genetic tests, said: "Finding a genetic cause for the patient's problems has helped her and her family to understand and manage her condition better. We can also look at members of her family with one abnormal copy of the gene, to see they are affected in more subtle ways that could increase their risk of obesity."

Professor Blakemore said genetic tests should be widely available for patients with severe obesity. "If people are diagnosed with a genetic condition like this one, we can look for other possible symptoms, and offer genetic advice to other family members if they want this. Diagnosis is very valuable to the patient. It helps to set realistic expectations, and can help them get the best possible treatment," she said.

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For more information please contact:

Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. Suzanne I.M. Alsters et al. 'Truncating homozygous mutation of carboxypeptidase E (CPE) in a morbidly obese female with type 2 diabetes mellitus, intellectual disability and hypogonadotrophic hypogonadism.' PLOS ONE, 29 June 2015. DOI: 10.1371/journal.pone.0131417

Open access article: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131417

2. About Imperial College London

Imperial College London is one of the world's leading universities. The College's 14,000 students and 7,500 staff are expanding the frontiers of knowledge in science, medicine, engineering and business, and translating their discoveries into benefits for society.

Founded in 1907, Imperial builds on a distinguished past - having pioneered penicillin, holography and fibre optics - to shape the future. Imperial researchers work across disciplines to improve global health, tackle climate change, develop sustainable energy technology and address security challenges. This blend of academic excellence and its real-world application feeds into Imperial's exceptional learning environment, where students participate in research to push the limits of their degrees.

Imperial nurtures a dynamic enterprise culture, where collaborations with industrial, healthcare and international partners are the norm. In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Imperial has nine London campuses, including Imperial West: a new 25 acre research and innovation centre in White City, west London. At Imperial West, researchers, businesses and higher education partners will co-locate to create value from ideas on a global scale.

http://www.imperial.ac.uk

3. About the National Institute for Health Research

The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website (http://www.nihr.ac.uk).

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