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Fighting the diabetes epidemic

Diabetes care in Ireland is “completely under resourced” and the Government needs to make treatment of the disease a much higher priority, including setting up a national islet cell transplant programme like those available internationally, a leading expert has told the Medical Independent (MI).

Notwithstanding this pressing need for more funding for diabetes care, there is a substantial amount of promising diabetes-related research being carried out in various institutions in Ireland, according to Dr Diarmuid Smith, former HSE Clinical Lead for Diabetes and now a member of the 3U Diabetes Partnership, which brings together the academic strengths of Dublin City University, Maynooth University and the RCSI to enhance education and research opportunities across the three partner institutions.

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Dr Diarmuid Smith

The Partnership, comprising clinicians and scientists from the three institutions, is committed to developing cutting-edge research into this chronic and costly disease in Ireland and aligns a number of interlinked areas of research into the condition extending from identifying and developing new molecules with therapeutic potential to providing world class diabetes care and treatments in the clinic.

Islet transplantation, a treatment not currently available for people with type 1 diabetes in Ireland, was a major focus of the fourth Annual 3U Partnership International Diabetes Conference entitled ‘Current Challenges in Diabetes Research’, which took place at the RCSI in Dublin earlier this year.

An islet cell transplant programme for type 1 diabetes patients should be part of the current pancreas transplant programme, which has moved from Beaumont Hospital, Dublin, to St Vincent’s University Hospital, Dublin, maintained Dr Smith, who is a Consultant Endocrinologist at Beaumont Hospital.

“Transplantation of islets, while never likely to be a treatment for all patients with type 1 diabetes, can be life-changing for some patients, particularly those who struggle to recognise and manage low blood sugar readings due to insulin treatment.

“Although this treatment has been available for almost 20 years in centres in North America and Europe, Irish patients are still not able to avail of it. We believe that it should be available for those patients in Ireland who would most benefit from it.

“We would love to develop the pancreas islet cell programme as a national programme. It is essential to develop the pancreas and islet programme together. A lot of it is down to political will, investment and infrastructural support.

“While I’m disappointed that the pancreas programme has been moved from Beaumont to St Vincent’s, essentially, I just want it to be a national programme that will work successfully and help all the patients in the country. It is logistically possible but it needs support for this to happen,” Dr Smith emphasised.

“This is a treatment for patients with type 1 diabetes, who have recurrent, severe hypoglycaemia. Their life is destroyed by recurrent low blood sugars and this is typically used as a treatment for patients who have failed in pump therapy — they’re on an insulin pump but they’re still getting recurrent low blood sugars.”

What we would like in the diabetes community is that that programme would be recognised both as a pancreas and islet cell programme and not just a pancreas programme on its own 

Type 1 diabetes affects about 23,000 people in Ireland and Dr Smith estimates that five-to-10 per cent of that group would be suitable for islet cell transplantation.

He outlined the elements required for a comprehensive transplant programme and the work that has already been done with the help of colleagues in the UK. “To develop an islet cell programme you would need a facility to be built that would be able to isolate and culture the islets. You would need scientists to be on call and you’d need the set up in a hospital to inject the islet. That costs a lot of money so we started to collaborate with colleagues in the UK.

“We planned to liaise with the scientists there and use their culture facilities and then fly the islets back to Ireland and inject them into a patient here. We collaborated with colleagues in Oxford, especially with Prof Paul Johnson (Director of the Oxford Islet Transplant Programme and Professor of Paediatric Surgery at the University of Oxford) and they were agreeable to that proposal. So that was potentially a runner.

“What we needed then was to develop the pancreas and islet cell programme together, as they’ve done in the UK.

“What we would like in the diabetes community is that the programme would be recognised both as a pancreas and islet cell programme and not just a pancreas programme on its own. We’ve had a number of meetings with colleagues and surgeons at St Vincent’s and they are agreeable to it being a pancreas and islet programme. So what the Government needs to do is put an infrastructure in place to make sure that happens. They need to recognise St Vincent’s as the pancreas and islet centre and put an infrastructure in St Vincent’s to facilitate the appropriate running of that programme. It’s like everything else; a lot of it comes down to resources, infrastructure, and support.”

Dr Smith explained why national recognition of an islet cell programme is so vital. “If there is no national recognition of an islet cell programme sometimes if the pancreas is not being used in conjunction with a kidney it gets left behind a little bit. That’s why national recognition is very important.”

Type 1 diabetes is becoming more common and the incidence is now doubling every decade. “We’re not sure why this is. It may be something in the environment that’s changing and driving the increase,” Dr Smith suggested.

“There’s quite a variation in the prevalence from country to country. The relative hotspots in the world are places like Finland and Sardinia, and Ireland is also a relative hotspot. But no matter what part of the world you’re living in it’s becoming more prevalent. We’re not sure why this is but some people say there’s a theory called the accelerator hypothesis that holds it’s partially due to changing diet and exercise, so that may be a driver of it even in type 1. Others think it could be driven by the hygiene hypothesis where you’re born with a genetic predisposition to developing it and something in the environment triggers an antibody response that destroys the cells of the pancreas.

“It’s thought that maybe your gut acts as a protector for this environmental trigger and because we now live in a more sterile environment the flora within the gut may have changed over the last 10, 20 or 30 years and that’s leading to an increase in this autoimmune type condition. But we’re not sure.”

Research

But the good news is that there is currently a tremendous amount going on in research, Dr Smith told MI. “The research on type 1 diabetes is focusing on trying to bring out new insulin, new testing devices, new monitoring devices, new insulin pump therapy. There’s a lot of research on developing an ‘electronic cure’, in which a pump acts as an artificial pancreas and the patient doesn’t have to worry about their blood sugar.

“There is also significant research going on in the area of transplantation, like islet transplantation and stem cell transplantation. With type 1 diabetes most of the research is going on in countries like the UK and US and in Asian countries, but some stem cell transplantation work is being done at the REMEDI centre in Galway and in other universities here.

“There’s also research that’s trying to find a vaccine, where you can identify someone with a very high risk of developing type 1 diabetes and you can give them a vaccine that might help or prevent it,” Dr Smith said. “Research is going on too to try to modify the antibodies and reduce their expression.”

At the RCSI, Dr Garry Duffy is leading the DRIVE (Diabetes Reversing Implants with enhanced Viability and long-term Efficacy) programme involving 14 partners from seven European countries that received €8.9 million in funding last year as part of the Horizon 2020 Research and Innovation Framework Programme.

“Essentially, he’s taking insulin-producing cells from a different source, like a pig or a cow, and he’s trying to put that in a protective envelope where it could be implanted into a human and those cells could release insulin appropriately,” explained Dr Smith, who is a collaborator on the clinical side. DRIVE’s five-year work plan will include laboratory testing, with a view to human testing at the end of the project.

Dr Smith said the EU funding for the programme was an enormous achievement because it is increasingly difficult to get research funding, particularly in Ireland.

With type 1 diabetes most of the research is going on in countries like the UK and US and in Asian countries but some stem cell transplantation work is being done at the REMEDI centre in Galway and in other universities here

“It’s partly a sign of the times. Research is often done by clinicians with an academic interest but they are being squeezed out and it’s now predominately being given to academics who do research only. There are pros and cons to this. Some people argue that it’s a good thing but I believe there’s a role for both. I’ve done research for the last 10 years, but I’m afraid I’m going to have to give it up because there’s really no funding for it.

“However, there is still lots of research being done in Ireland on diabetes. One of my colleagues, Prof Tim O’Brien [Director of REMEDI, at NUI Galway] is doing a lot of significant stem cell work. Another colleague, Prof Fidelma Dunne in Galway, also does incredible work. My own group does work on type 2 diabetes, looking at vascular risk, and I collaborate with Dr Phil Cummins of the School of Biotechnology, Dublin City University, looking at biomarkers.”

Ulcers

One of the complications of diabetes is that nerves in the lower legs and feet get damaged, which increases the risk of ulcers forming. Other aspects of diabetes, such as poor blood supply to the feet and a compromised immune system, mean the wounds can be hard to treat and slow to heal.

Diabetic foot ulcers are costly to the health system. Some 15 per cent of people with diabetes develop foot ulcers and 70 per cent of ulcers re-occur within five years and put the individual at risk of needing an amputation. And if an infection enters the wound and spreads to the blood stream it can threaten the life of the patient.

At the University College Dublin Charles Institute, Prof Winxin Wang and his group are developing a temperature-responsive dressing that can be placed on a chronic diabetic wound and deliver stem cells to the site. This new polymer-based system will contain stem cells derived from fat tissue and it will also contain key ‘extracellular matrix’ biomolecules such as hyaluronic acid, collagen or gelatine to support the stem cells and help them to grow.

This smart wound dressing will be liquid at room temperature, but when it is applied to the wound, it will turn into a hydrogel thus forming a dressing as well as a reservoir system to secrete essential molecules for accelerated wound healing in chronic diabetic ulcers.

Meanwhile, earlier this year, Ms Andrea Mahon, a PhD student in the Discipline of Podiatric Medicine at NUI Galway, was awarded a prestigious Journal of Wound Care Award for The Best Laboratory/Pre-Clinical Study for her work on designing a preclinical study to assess topical stem cell therapy in a diabetic wound model.

A stem cell clinical trial in diabetic foot ulcers will be planned by the outcome of this research.

Prof Caroline McIntosh, Head of Discipline of Podiatric Medicine, NUI Galway, helped supervise the research and said: “This is a fabulous achievement, which highlights the high quality of research being undertaken in wound healing and tissue repair at NUI Galway. Diabetes is one of the leading causes of lower limb ulceration and amputation. Diabetes-related foot ulcers are challenging to manage, with many failing to respond to standard wound therapies. There is a need to research advanced therapies for application on non-healing wounds. The findings of Andrea’s research will help in the design of first in human studies of Mesenchymal stem cell application for non-healing neuropathic diabetic foot ulcers.”

Under-resourced

But while progress is being made on many research fronts in Ireland, Dr Smith believes that diabetes care itself is “completely under resourced”. His ‘bucket list’ of improvements includes more consultants around the country within hospitals to manage type 1 diabetes. “We also need more resources to deal with the improved technologies in the management of type 1 diabetes. We need more nurses, dieticians, and so on, both in the hospitals and in the community. We need to upskill our primary care colleagues to manage type 2 diabetes. We need more podiatrists to manage diabetic foot disease. At transplant level we need to develop national services, such as an islet cell and pancreas programme, and we need to put more work into the pancreas programme at St Vincent’s.”

On the plus side, Dr Smith is heartened by the development in recent years of the national diabetic retinopathy screening programme, Diabetic RetinaScreen, which he calls a “fantastic development”. If diabetes is not well managed, he emphasises, it can lead to heart disease, strokes, kidney failure, nerve damage, blindness, and birth defects in babies born to women with diabetes.

“Foot care is a bit better because we have a national model of foot care, but you have to realise that five years ago there were only three podiatrists involved in diabetes foot care nationally when the recommendation was 90 to 100. We’ve gone up to maybe 20 now, but there’s still a long way to go.

The rising incidence of diabetes globally

Rates of diabetes in Ireland have grown by up to 70 per cent since 1980, according to a major study published in The Lancet. This is in line with a worldwide surge in the same period.

Since 1980, the number of adults with diabetes worldwide has quadrupled from 108 million to 422 million in 2014, according to the World Health Organisation (WHO) study. The findings provide the most comprehensive estimates of worldwide diabetes trends to date and show that the disease is fast becoming a major problem in low and middle-income countries.

“Diabetes has become a defining issue for global public health. An ageing population, and rising levels of obesity, mean that the number of people with diabetes has increased dramatically over the past 35 years,” said Prof Majid Ezzati, study senior author, from Imperial College London.

Between 1980 and 2014, diabetes has become more common among men than women. Adjusting for age, the incidence of the disease increased from 4.3 per cent to 9 per cent for men, and from 5 per cent to 7.9 per cent for women.

In Ireland, the rate for men grew from 4.3 per cent to 7.3 per cent, and for women from 3.3 per cent to 5.1 per cent.

The study includes data from 751 studies totalling 4.4 million adults in different regions of the world. The study estimates age-adjusted diabetes prevalence for 200 countries.

Although there was an increase in overall rates (crude prevalence) of diabetes in many countries in Western Europe, age-adjusted rates were relatively stable, suggesting that most of the rise in diabetes in Western Europe between 1980 and 2014 was due to the ageing population. The prevalence of the disease was lowest in Switzerland, Austria, Denmark, Belgium, and the Netherlands.

 In contrast, rates increased significantly in many low and middle income countries, such as China, India, Indonesia, Pakistan, Egypt, and Mexico. No country saw a significant decrease in diabetes prevalence.

The researchers calculated the annual worldwide cost of the disease to be more than €900 billion per year, which included costs related to treatment and managing complications, such as amputations. However, they pointed out that they had not included the cost of work days lost due to diabetes and added that the overall costs would be much higher if these were also incorporated.

“This is the first time we have had such a complete global picture about diabetes and the data reveals the disease has reached levels that can bankrupt some countries’ health systems,” the study noted.

The researchers said the biggest risk factor for type 2 diabetes is obesity, levels of which are “soaring out of control”. But they also noted that genetics and foetal and early-life conditions may also have a role to play.

There is increasing evidence that the interaction of genes and the environment plays a role in diabetes, the study found. “For example, certain genotypes may increase the risk of diabetes especially in people with unhealthy lifestyles. In addition, inadequate nutrition during pregnancy and in early life may increase the risk of diabetes later in life. Therefore, long-term diabetes prevention should address nutrition in every stage of life.”

The study did not differentiate between type 1 and type 2 diabetes, but most (85-95 per cent) cases of adult diabetes are type 2 so the observed rise is likely to be mostly due to increases in type 2 diabetes.

NUI Galway will play host to a major three-day international symposium focusing on improving health outcomes for young adults with type 1 diabetes from 22-24 June. For full programme details or to register for free visit goo.gl/3I1zMG. For further information contact Dr Lisa Hynes in NUI Galway’s School of Psychology on 091 494458.

“There is a huge deficit in the country in relation to diabetes and pregnancy care. This is a major risk area. That has to improve. We also have a lot of work to do in the management of obesity because diabetes and obesity go hand in hand. We need to do more work on paediatric diabetes and we need to do a lot of work on type 2 diabetes and primary care. We’ve got huge numbers increasing all the time with type 2 diabetes and then with type 1 diabetes the challenge of injecting yourself four times a day makes it a difficult disease to manage.”

Type 1 is about more investment around the hospitals, he says, and type 2 is about developing the infrastructure and communications between the GP and the hospital.

Dr Smith would like to see a new government making diabetes treatment and care a much bigger priority because diabetes is affecting up to 250,000 people here.

“Any government I believe has a responsibility to do this. And if you invest in diabetes care now it pays off down the line. Diabetes is covered by 10 per cent of the healthcare budget but 60 per cent of that budget is spent on complications that are preventable. The problem is that it takes a bit of time and every government we have wants a result within six months or a year.”

Chronic illnesses do not work like that, he emphasises. “We need a government that sees if we invest in this it will save money in five, 10, 15 or 20 years. That’s why we need a government that has a bit of vision and a bit of cop on, that says, ‘let’s invest now for the next five, 10 years or 20 years’, not just for the next year.”

In a global context, the WHO diabetes report (see panel) echoes many of Dr Smith’s sentiments and highlights the need to step up prevention and treatment of the disease.

Health-promoting environments

Measures needed, it says, include expanding health-promoting environments to reduce diabetes risk factors, like physical inactivity and unhealthy diets, and strengthening national capacities to help people with diabetes receive the treatment and care they need to manage their conditions.

“If we are to make any headway in halting the rise in diabetes, we need to rethink our daily lives: To eat healthily, be physically active, and avoid excessive weight gain,” said Dr Margaret Chan, WHO Director-General.

“Even in the poorest settings, governments must ensure that people are able to make these healthy choices and that health systems are able to diagnose and treat people with diabetes.”

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