"Collaborative research is key to tackling diabetes complications. It accelerates impact bringing benefit to patients, scientists and the health service" says Professor Catherine Godson, Director of the UCD Diabetes Complications Research Centre (DCRC) at the UCD School of Medicine and UCD Conway Institute.

Expertise across a breadth of clinical and scientific disciplines at the DCRC is brought to bear on the investigation of how best to tackle the serious and life limiting complications of diabetes including heart disease, stroke and kidney disease. Diabetes and its associated complications consume 10% of our national healthcare spend. "Our spirit of collaboration also extends to patients," says Godson. "The DCRC will host The Patient Voice in Diabetes Research on November 14, World Diabetes Day, so we can share our news and get their feedback."

Collaboration has already resulted in some major steps forward.

 

Research to reverse diabetic complications

 

Godson and her colleagues are researching the role of inflammation as a driver of diabetic kidney disease (DKD), heart diseases and stroke, in a bid to find a new treatment to prevent - and even reverse - its effects.

Currently there are no drugs that stop or reverse DKD. Godson says: "Failure to resolve chronic inflammation is a causal factor in this. In healthy conditions, inflammation usually resolves in response to messengers generated by the body leaving no scars, but inflammation that does not resolve sufficiently leads to scarring and eventual organ failure.

"We have worked with UCD synthetic chemist, Professor Patrick Guiry and his team, to generate molecules that mimic the molecular messengers that tell the body to resolve inflammation. Using these compounds, in research conducted with collaborators in Australia, we have been able to reverse both kidney and heart disease in diabetic animals. Using human tissue, we have also seen that these molecules can dampen inflammatory reactions in blood vessels.

These synthetic molecules might, in future, lead to the development of drugs that could transform DKD treatment. Other investigations, as part of a major international effort, are looking for genetic reasons as to why not everyone with diabetes develops complications, an approach that Dr Eoin Brennan says “will help doctors to tailor or ‘personalise’ treatments”.

 

How diet and nutrition can help

 

The role of diet and nutrition in diabetes is the subject of research by Helen M Roche, Professor of Nutrigenomics at the UCD Conway Institute and UCD Institute of Food and Health.

"Nutritional research requires a lot of hard scientific evidence, and the DCRC offers a bridge to other scientists, such as Dr Fiona McGillicuddy who, from a pharmacological perspective, also studies the impact of dietary regulation of cardiovascular risk related to obesity and diabetes," says Roche.

"I have colleagues in the nutrition group and public health team, and in clinical medicine. We are all tackling diabetes from different perspectives, so combining knowledge helps everyone - including patients." For example, Professors Cecily Kelleher, Pat Wall and Dr Catherine Phillips lead the field in public health and, together with collaborators at the HRB Centre for Health and Diet Research, are studying obesity across generations.

 

Link between children with obesity and their grandmothers

 

Interesting recent findings indicate a link between obesity in children and their maternal grandmothers, but not other grandparents. In addition, other colleagues from the School of Medicine include Professor Donal O’Shea, who leads the national taskforce on obesity and Professor Fionnuala McAuliffe  who investigates maternal and infant nutrition at the National Maternity Hospital.

Roche's research has revealed that, while some diets lower the risk of diabetes in some people, it's not the same for everyone. "There is more to it than just 'calories in-calories out," she says. "No single diet will reduce everyone's risk of obesity or diabetes." This concept is referred to as Personalised Health.

She explains: "We are looking at why some individuals are more at risk than others of developing problems from eating saturated fats, and how to mitigate their risk."

A group of teenagers who were overweight or obese were given an anti-inflammatory nutritional 'cocktail' and two portions of oily fish (in pill form) daily. Roche reports: "40% responded showing lower insulin and glucose levels - but 60% didn't. We are using biomarkers to try to identify people who will respond to particular dietary interventions." So, we can target individuals who will benefit and work on alternative therapeutic approaches for those who do not.

 

How the gut talks to the brain

 

Professor Carel le Roux, Co-Director of the Metabolic Medicine laboratory, at the UCD DCRC, is researching how the link between the gut and the brain can help prevent - and even reverse - diabetes complications.

"Here, we can discuss theory, work in the molecular biology laboratory, and test treatments on the same site. It takes research right from the bench to the bedside," he says.

"We also have access to local clinical colleagues, including Miss Helen Heneghan (Consultant Bariatric Surgeon at St Vincent’s University Hospital) and Professor Donal Brennan (Consultant Surgeon at the Mater Misericordiae University Hospital) and international collaborations. Few centres anywhere have this capacity."

le Roux explains: "Patients with Type 2 diabetes have a deficiency of the hormone GLP-1, which signals from the gut to the pancreas to make insulin - but it also tells the brain when you have eaten enough, so people lacking GLP-1 do not feel full after a meal."

Overeating results in a layer of fat building up between organs such as the liver and pancreas, causing insulin resistance. "It's like a wall, and there is not enough insulin to push the glucose from the bloodstream into the cells. Thus, the glucose accumulates in the blood making the problem worse," says le Roux.

There are three current treatments for low GLP-1: specific diet and exercise, which leads to diabetes remission in two out of ten patients; injecting extra GLP-1, which works in three out of ten; and rerouting the gut to send food quickly to the small bowel, where GLP-1 is made, to boost production - this works for five out of ten people.

le Roux says: "We are researching which of the three options works best for individual patients and combining all three options to reverse complications in the sickest patients. Our experiments are starting to show that this is possible."

Dr Neil Docherty, Co-Director of the Metabolic Medicine laboratory at the UCD DCRC is exploring another angle to optimise the control of blood sugar in patients with diabetes. In a Health Research Board funded collaboration with international experts from Monash University in Melbourne, Docherty and his team are examining whether a hormone normally associated with skin colouring might also have applications in diabetes. Docherty says: “Curiously, a hormone called alpha-MSH, which is released from the brain and plays a role in skin pigmentation, is also elevated in the bloodstream after eating. We have evidence demonstrating that this surge of the hormone after eating helps our muscles to burn glucose, hence helping with blood sugar control. Derivatives of the hormone hold promise as novel anti-diabetic drugs and studies in humans are now underway as a result of the Ireland-Australia research collaboration.

The DCRC team of Principal Investigators also includes Dr John Crean, who is working on re-engineering damaged cells, Dr Orina Belton working on fundamental mechanisms governing atherosclerosis regression and macrovascular complications of diabetes and Dr Daniel Crean working on inflammation and re-purposing of existing therapeutics for the treatment of organ damage in diabetes.

Funding helps collaboration - funders include Science Foundation Ireland, Irish Research Council, Health Research Board, The European Union, Wellcome Trust, the National Institutes of Health, the Juvenile Diabetes Research Foundation, European Renal Association (ERA), European Foundation for the Study of Diabetes and the bio-pharma industry.