In diabetes research, we need to forget the idea of an ‘average’ patient

29 Nov 2017

Dr Donal O’Gorman, interim director, National Institute for Cellular Biotechnology, Dublin City University. Image: DCU

With diabetes skyrocketing globally, researchers such as DCU’s Dr Donal O’Gorman are facing new realities.

According to the World Health Organisation, diabetes has now been declared an epidemic. It affects 422m people globally, with 90pc of these having the type 2 variant commonly associated with obesity and ageing.

With such an enormous challenge ahead – and even now – many researchers are investing huge amounts of time and energy into finding out how exactly the disease develops and whether it can be prevented – or, if not, treated.

One such researcher is Dr Donal O’Gorman from Dublin City University (DCU), interim director of the National Institute for Cellular Biotechnology (NICB).

The NICB is a major focus for cell and molecular biology research in Ireland, and O’Gorman is leading his own group to investigate the regulation of energy metabolism, with a particular interest in diabetes.

He recently worked with the European Space Agency and the 3U Diabetes Consortium on a bed-rest study, which found that the body’s ability to regulate metabolism is tightly linked to the number of mitochondria (the powerhouse of our cells).

What inspired you to become a researcher?

There are two clear periods of time that inspired me to become a researcher. I have a varied background, initially starting with physical education teacher training at the University of Limerick.

During my time there, the National Coaching and Training Centre (NCTC) was established to test and provide support for elite athletes in Ireland. There was a call for student ‘helpers’ and I responded with a number of others.

As soon as I became involved in this process, I knew straight away that I wanted to pursue a career understanding the physiology of performance – though, at this time, I knew relatively little about research opportunities.

The director of the NCTC decided to take up a position at Penn State University and, within 18 months, he provided me with an opportunity to undertake an MSc under his supervision. It was during this time in the US that I was exposed to the knowledge and techniques that would form the basis for my career.

Can you tell us about the research you’re currently working on?

The main focus of my work is the study of energy metabolism. I am particularly interested in the small but subtle changes that take place in the early development of disease, or those that are easily responsive to change following muscle contraction.

I work on the basis that these ‘early adapters’ are important for maintaining normal function and health.

This work includes an understanding of how energy expenditure is regulated at rest, during daily activities, and how it changes with ageing and disease onset. As part of this work, we study the fuels the cells use to produce the energy needed, mainly focusing on how carbohydrates and fat get broken down or stored.

Finally, we link these changes in energy metabolism to other physiological processes – for example, how sensitive the cells are to insulin and how this might influence the rate at which glucose is transported into cells. When this becomes impaired, it contributes to the development of type 2 diabetes.

In your opinion, why is your research important?

The rate at which type 2 diabetes is developing in Ireland and around the world means that healthcare systems are not able to cope with the management and treatment of the disease.

In 1985, it was estimated that 30m people had diabetes, but the latest estimates suggest it is expected to grow to 642m by 2040.

As most people with diabetes develop complications that affect the cardiovascular system, kidneys, eyes and the nervous system, the overall impact on health is far greater than just high blood glucose, while the overall cost to treat diabetes is a major component of total healthcare spending.

What commercial applications do you foresee for your research?

The measurement of small and subtle changes in metabolism requires the development of new techniques and models. We are currently working on a system that will allow for better detection of respiration in contracting cells, and would be a valuable and low-cost tool for screening different compounds.

We are also working on a technique that would advance our ability to quantify energy metabolism from fat. In the past, DCU licensed the MyEnergy software, an Enterprise Ireland commercialisation project with Cathal Gurrin, to predict energy expenditure using a range of wearable sensors.

What are some of the biggest challenges you face as a researcher in your field?

We have for many years based the effectiveness of a treatment on the ‘average’ response during a trial.

Yet, it has become apparent that most people are not ‘average’ and we need much better patient characterisation and stratification in order to identify groups of individuals that respond in a similar manner.

A major challenge we face is to better understand ‘integrated physiology’. Most researchers study one system in great detail and, for me, this would be skeletal muscle metabolism. However, a disease like type 2 diabetes affects so many different tissues in the body that it is important we understand how all of these systems, collectively, lead to the development and progression of the disease.

Some of my biggest frustrations include not being able to execute ideas quickly enough, or not having the facilities/resources to investigate in the required depth. In many cases, the good ideas I have get addressed by someone else before I get the chance to finish.

Are there any common misconceptions about this area of research? How would you address them?

The biggest misconception about type 2 diabetes is that all patients are relatively similar. Yes, they have high blood glucose levels, but the reason it becomes elevated may be due to a variety of reasons, including their genetic predisposition, how well their pancreas can produce insulin and how well that insulin acts around the body.

Our experience suggests that patients respond to treatment very differently and that it becomes difficult to individualise the management of the disease.

Patients with type 2 diabetes around the world can appear very different. In western Europe and North America, type 2 diabetes is associated with obesity but in Asian countries, patients can often be normal or even underweight but still have high glucose. We need to better understand the factors that lead to diabetes in a global context.