A recent conference in Dublin, entitled “Innovations in Diabetes”, focused on new approaches and research in clinical care and science that are building towards a cure for diabetes while simultaneously shedding light on what causes the disease.
Speaking to IMN at the conference, Professor Chris Newgard, Professor of Pharmacology and Cancer Biology at the Sarah W Stedman Nutrition and Metabolism Centre, North Carolina, US, explained how similar principles used to personalise and target cancer care after years of research are now being applied in type 2 diabetes.
Like in some forms of cancer, where mutations in a patient’s genetic profile can determine targeted treatment, Prof Newgard is leading studies that hope to eventually do the same for sufferers of type 2 diabetes and obesity. He is an expert in metabolomics, which is what he spoke about at last week’s conference.
Type 2 diabetes is caused by a complex set of interactions between genetic and environmental factors, researchers now know. Recent work has shown that the condition is in fact is a group of disorders associated with polymorphisms in a wide variety of genes.
“Everyone has heard of genomics – large scale studies of genes in the body – and what we try to do with metabolomics is comprehensively measure all the small molecule metabolites in the body,” Prof Newgard explained. “The over-arching value of the technology, from my perspective, is that it basically allows us to measure all the chemical changes that occur in the body.
“Basically, the products of the metabolic pathways are what we are measuring with our technologies. It gives us an up to the minute chemical phenotype of a person. What we then do with this tool is compare subjects with conditions or diseases such as diabetes with normal subjects – go out and recruit 70 obese, insulin-resistant patients and compare them to a similar number of lean, insulin-sensitive patients and ask: are there any striking differences here that we never noticed before? Are there individual metabolites or perhaps clusters of metabolites that differentiate obese insulin-resistant patients from lean?”
At the conference in Dublin Prof Newgard presented this exact experiment and showed that he and his team did, in fact, find something unanticipated.
“We found that the metabolite cluster most strongly associated with insulin resistance was one involving the branched-chain amino acids and related metabolites,” said the Professor. “If you had asked us (before this) what class of metabolites would be most strongly linked with insulin resistance, we would have said fatty acids and related molecules. But this is not so; it is actually amino acids. That gave us a clue that led us into animal experimentation to try understand what this means.”
When the team fed branched-chain amino acids to laboratory rats they created insulin resistance, which had features that were unique compared to the insulin resistance one can get from just feeding on a high-fat diet.
“From a public health persective, we are bombarded with information about the problems of excess fat and sugar in our diets – and when you think about the American brand of nutrition, we have no prejudice against any food group. We eat whatever they put in front of us – and that McDonalds burger doesn’t just have fat, it has protein in it. What our work is calling out is the possibility that we have underestimated the contribution that excess protein consumption – on top of too much fat and sugar – can make to the development of metabolic disease,” Prof Newgard said.
Prof Newgard believes we are facing a “tsunami” of type 2 diabetes.
“The thing is, we all know the horrifying statistics on the rise of type 2 diabetes and obesity since the 1980s but there is not much we can do about it,” he remarked. “Over 65 per cent of Americans are overweight and we can expect a pandemic of diabetes to go hand in hand with that, there is no way around it. There is no single drug currently that really treats the disease. We look ahead and see a tsunami wave, not just because it affects individuals and families but because of the huge economic costs.”
He agrees, though, that hope lies in research and continuing innovation.
Type 1 diabetes
One of the most hopeful trends in diabetes research is the quest to develop an artificial pancreas, a device that could make the lives of people with type 1 diabetes safer, healthier and easier – possibly within the next few years. This is according to leading diabetes specialist Dr Roman Hovorka, Principal Research Specialist at Cambridge University, UK. Speaking to IMN at the conference in Dublin, Dr Hovorka said the technology already exists, and what is needed are trials in outpatients to determine how it works outside hospital.
“The next step is to move studies of an artifical pancreas from controlled conditions in a hospital setting out to real life,” said Dr Hovorka. Currently he and is team are investigating an overnight “closed-loop” system, which links continuous glucose measurements to insulin delivery. They want to see whether closed-loop insulin delivery can control overnight blood glucose.
“One challenge is that there are currently no dual pumps that can deliver both insulin and glucagon simultaneously. We have to work closely with the regulatory authorities as these are a new type of product. If someone was dying one would have to have very advanced solutions, but because in diabetes it is an ongoing condition, the authorities need very very good evidence that these devices provide a benefit over existing systems,” said Dr Hovorka.
Type 1 is typically harder to manage than type 2 and this treatment will “transform patients lives”, he added. However, it won’t be suitable for all patients, as the technology needs to be managed and some patients may find this difficult.
“It is not a biological cure. From my point of view the technology is there – before the first car was built they had an engine, then a wheel... they just needed to put them together and use it. As we go along the new generation (of devices) will get better and better.”
According to Dr Hovorka, perhaps the best part of the technology is that an artificial pancreas is there all the time.
“It can make decisions while a person sleeps. In a not too distant future, people with diabetes may finally be able to rest easy.”
A 10-year vision for research and care
Over 31 million people in the EU suffer from diabetes, and researchers acknowledge that they must respond to this problem with studies that can be translated into effective treatment that will quickly reach patients.
At the conference, consultant endocrinologist, formerly of St James’s Hospital, Dublin, Professor John Nolan, stated that Europe’s potential to “lead the world in diabetes research” is not being maximised because of the lack of a common research network.
He told the conference that new data from a European Commission-driven research initiative called DIAMAP shows that there is significant deficit in the level of funding across the European Union provided for diabetes research. The figure is estimated at approximately €500,000,000 compared to the amount spent on treating the condition, which is estimated to be more than €50 billion annually.
Earlier this month, Prof Nolan took up his position as CEO and head of the Steno Diabetes Centre in Copenhagen, Denmark. He left Ireland with an admirable legacy – setting up the diabetes clinic in St James’s Hospital, which now sees over 9,000 patients a year.
“The Steno Centre is a one-stop shop when it comes to diabetes care and research,” Prof Nolan explained. “It’s an endocrinological, chiefly diabetological research hospital and international teaching centre that specialises in treating and managing diabetes.”
His new position has allowed Prof Nolan make comparisons between the Danish model for chronic disease management and the Irish one.
“The problem in Ireland is that although people work very hard, the frontline is extremely stretched and there’s a lack of resources available to them. There’s no doubt that chronic-illness areas, such as diabetes care, will struggle because it’s so hard to keep acute services afloat.”
Diabetes rates are very similar all across northern Europe, he continued. “According to the most up-to-date data, the rates of type 1 and type 2 combined sit at around six per cent of the population. Of this, around 90 per cent is type 2. However, we know that there’s still not enough screening for pre-diabetes of people aged between 40 and 75 – this is when people are teetering on the edge of developing the condition. Studies show that around 10 per cent of the population are in the pre-diabetes category.”
