Dr Gordon Moran
Title: Anabolic resistance and abnormal muscle function across the nutritional spectrum: a pilot study in Crohn’s disease
Project Start Date: 1 December 2015
Completion Date: 1 December 2016
Weight loss, including loss of muscle, is a very common problem in Crohn’s disease in childhood. Even when the child is well muscle weakness can be a persistent issue. This is important as it can lead to chronic lethargy, physical inactivity and a poor quality of life.
It is not known what causes this loss of muscle mass and function. It is possible that general lack of appetite, problems absorbing food and low levels of physical activity are the key contributors. However we think that the gut inflammation that characterises Crohn’s disease could itself be affecting muscle function. It is possible that ‘inflammatory signals’ from the gut travel in the bloodstream to muscles and cause them to suffer from something called ‘anabolic resistance’. This means they cannot grow properly even when provided with food. Muscles may also become ‘insulin resistant’ where they stop absorbing sugar because of the inflammation, a problem often associated with diabetes. This is another factor that may stop muscles working and growing properly.
Our project aims to investigate whether children with Crohn’s disease (even when well) suffer from anabolic and / or insulin resistance. This information will help us plan further work to see how we can use exercise, nutrition and / or various medicines, to improve muscle mass and function.
Dr Francis Stephens and Dr Kostas Tsintzas, muscle physiologists from the University of Exeter and University of Nottingham, respectively, are the key collaborators. Both have many years of experience and expertise in investigating muscle function in a variety of populations. Therefore are ideally placed to complement the expertise of the Lead Investigator, Dr Gordon Moran.
Dr Sian Kirkham is a clinical paediatric gastroenterologist and will aid on recruitment from the Nottingham Children’s Hospital.
The project will study 30 children in all. 20 who have been diagnosed with Crohn’s disease, of which 10 will have had more severe disease and 10 with milder disease. All these children will be well when they are studied and between the ages of 11 and 18. 10 healthy volunteers, of similar age and sex to the patients will also be studied, providing a group for comparison.
The study will consist of one main visit to the laboratory where we will investigate the children’s response to food and their ability to perform simple handgrip exercises. This information will tell us whether their muscles are suffering from anabolic and / or insulin resistance. It will involve taking small blood samples. We will also measure the child’s metabolic rate i.e. how much energy they are using just to rest on the bed. We will do this by measuring how much oxygen they are breathing in and how much carbon dioxide they’re breathing out. This data will also tell us how much fat and carbohydrate they are using as fuel. Additionally we will collect information on their eating and activity habits and lifestyle.
After all of the visits have been conducted and samples & data analysed, a final report will be produced. The project will begin in 01/12/2015 with the main work being completed within 12 months. A final report will be completed by 01/12/2016.
Findings from the project itself will serve as pilot data for further downstream studies. Success in this project will be measured in a number of ways: recruitment and finalisation of all the studies, publication and presentation of our findings in appropriate meetings and journals and increased understand of the altered muscle physiology in the groups studied. This will hopefully allow further detailed work investigating how exercise or pharmacological treatment altering fat content within the muscle might improve and normalise muscle physiology hence improving fatigue and quality of life in children with Crohn’s disease.
The Core fund has provided much need pump-priming funding to allow me to get pilot data and track record in this very competitive field. This will hopefully allow further detailed work investigating how exercise or pharmacological treatment altering fat content within the muscle might improve and normalise muscle physiology hence improving fatigue and quality of life in children with Crohn’s disease.Dr Gordon Moran