Dr Gordon Moran (Crohn’s Disease)

Dr Gordon Moran - 2015 BSPGHAN-Core Development Award
Dr Gordon Moran – 2015 Core / BSPGHAN Development Award

Institution: University of Nottingham

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 March 2017

Summary:

Weight loss, including muscle loss, in Crohn’s disease during childhood is a common problem. Even when the child is well, a large proportion of patients never grow their muscles back to normal. This is important as muscle loss has a negative effect on physical activity, patient wellbeing and quality of life. Moreover, physical activity plays a major role in normal growth development, physical fitness, bone strength, intellectual and social functions of children.

When inactive, the muscles tend to accumulate fat which stops the muscles from growing any further. This may lead to further physical inactivity and a further reduction in muscle mass and function. The inability of a muscle to grow is called anabolic resistance. Additionally, when muscles accumulate fat they are less able to respond to insulin, the hormone that allows muscle to absorb glucose (a type of sugar). This is called insulin resistance, a problem often associated with diabetes.

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 Dr Moran and his colleagues wanted to explore whether the gut inflammation that characterises Crohn’s disease could itself be affecting muscle function.  They thought it was possible that ‘inflammatory signals’ from the gut travel through the bloodstream to the muscles and cause them to suffer from anabolic and insulin resistance.

The researchers carried out a pilot study, co-funded by Core and BSPGHAN, to investigate their idea that children with Crohn’s disease (even when well) suffer from anabolic resistance. Children who participated in the study were asked to come into the laboratory to have an intravenous cannulae placed in the forearm and elbow of the non-dominant arm. The participants were given a meal in the form of a protein drink followed by an energy drink taken an hour afterwards. Blood samples were taken every 20 minutes during 3 hours. Information on the children’s metabolic rate, total muscle mass (using an X-ray), habitual food intake (obtained via phone calls during that study week), quality of life and physical activity (wearing a sensewear arm band for a few days) were also collected.

When they analysed all the data, the researchers found out that, in contrast to healthy children, children with Crohn’s disease do not have the capacity to build muscle after a meal.  The muscles of children with Crohn’s disease initially respond positively to the stimulus given by the meal i.e. they are not technically anabolically resistant.  However, they cannot sustain this response and so overall do not make extra muscle protein after eating.  This means the children are unable to build back up the muscle they have lost during the active phase of their disease and can only maintain what the muscles they have.

Understanding that children with Crohn’s disease, even when well, are unable to build muscle protein after a meal means we now know why they can’t grow their muscles back to normal size.  We can now design further studies to test interventions that may be able to solve this problem.

Further analysis of the current data is needed to understand if there are differences within this group of children with Crohn’s disease in terms of gender and / or treatment.  Once this is complete a further intervention study will be designed to see if this problem can be overcome with, for example,  medicines to reduce the breakdown by the body of muscle protein and/or with a high protein diet to boost the muscle’s response to a meal.

If we are able to successfully test an intervention we may be able to ensure children with Crohn’s disease do fully regain lost muscle mass when well, and so reduce fatigue and improve quality of life.

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