FEATURES

Ten of the best, ten years on: Reversing the effects of diabetes

Photo credit: University of Sydney

Professor David James

Garvan Institute of Medical Research | $690,000

Since 2008 NHMRC has funded over $680 million in diabetes research1

Professor David James was featured in NHMRC’s Ten of the Best 2008 publication for his research into type 2 diabetes, specifically looking for new compounds for treatment. Ten years later, NHMRC decided to catch up with Professor James to see what has changed in the understanding, treatment and prevention of type 2 diabetes.

A lot has advanced since 2008, with a significant shift in the thinking on how to combat type 2 diabetes. A revolution in gathering and analysing large amounts of data has seen a huge leap forward in understanding how our bodies work.

For Professor James this means he has been able to produce a map to explore the metabolic process involved, not only in insulin resistance but also the processes involved in diet and exercise—which are closely linked to type 2 diabetes.

‘Today we routinely work hand in glove with mathematicians, statisticians and physicists. We have developed the technology to be able to measure how the proteins in our cells behave from countless types of modifications,’ Professor James said.

‘We used highly sophisticated mathematical approaches to try to understand how relatively simple molecules, like insulin, trigger complex biology in target cells. Specifically, looking at the outcomes after insulin engages its receptor on those cells.  We have identified literally thousands of changes within seconds of insulin binding. Think of it – this is exactly what occurs in us every time we eat.’

Professor James explained how the lifestyle choices that lead to type 2 diabetes are strongly linked to socioeconomics and where you live in Australia. This is entwined with biochemical processes in each cell that have been evolving for over four billion years—in the very first cellular life-forms on earth.

‘In my opinion the real challenge in metabolic diseases, such as type 2 diabetes, is understanding how the evolved genotype interacts with the modern-day lifestyle choices we make.’

Professor James has received NHMRC funding since 1990 to undertake research into metabolic processes such as type 2 diabetes. Now at the Charles Perkins Centre at the University of Sydney, he is turning his attention to how the body processes what we eat and how that relates to metabolic disease like type 2 diabetes.

‘Understanding why some people become obese and why not all obese people acquire type 2 diabetes will really not only change how we treat patients but also the food industry itself,’ Professor James said.

‘We now suspect that understanding how each patient’s body interacts with different ratios of carbohydrates and fat is critical to determining outcomes, such as feelings of satiation or fullness.

‘This same understanding will also have huge impacts on how we treat patients with medications for type 2 diabetes. At the moment patients are indiscriminately put on medications when we know each medication only works in a subgroup of the population.  In the future we can envisage that patients will be screened for how their bodies react to medications—meaning they will be able to go straight onto the medication that will work for them,’ he explained.

In the next decade, Professor James hopes to see the development of, what is termed—precision medicine—for not just a cure but the prevention of type 2 diabetes.

‘It’s not simple—we are working against a very deliberate evolutionary process. We will need to work more on human populations, which will be expensive and take time,’ he said.

‘Every time I get an NHMRC grant my heart races a bit not just because it makes me feel good but because I know I can continue to provide the salaries and resources to keep these young researchers going.'

‘Behind me stands a team of fantastic people from all over the world. They are driven and absolutely excited about what they are doing, and feel privileged to get funding to do this.

‘They are going to be tomorrows hope. That is what this is all about. It is about creating the next generation of people and without NHMRC you couldn’t do that.’


1Source: NHMRC Research Grants Management System (RGMS)