Category: New content

In a new series of films on Horizons, leading researchers and clinicians from around the world talk about the journal articles that have left a deep impression on their understanding and practice in the field of diabetes.

Scientific discovery is a slow, painstaking business. Eureka moments are few and far between. Even so, it’s the breakthroughs that stick in the mind. Those turning points – usually accompanied by a much pored-over journal article and hinging on the sharing and accumulation of knowledge over many years – when, for the scientific community, the penny finally drops and our collective understanding advances.

The history of diabetes research is unusually blessed with such moments. The Diabetes Control and Complications Trial, which conclusively demonstrated the importance of tight glycaemic (and blood pressure) control in preventing the complications of type 1 diabetes. The United Kingdom Prospective Diabetes Study, which did much the same for type 2 diabetes. And of course, just over a century ago, the discovery of insulin itself.

We wanted to know which trial results and articles had been breakthrough moments for our authors and collaborators. Starting earlier this year, whenever we were filming a module or panel discussion, we began asking presenters or participants to choose the diabetes-related journal article that had had the biggest impact on them, and to explain how it had affected their understanding of diabetes and their practice as a researcher or clinician. The result is a new film series -‘Gamechangers’ – which starts on Horizons this week.

To kick the series off, EASD President Professor Stefano Del Prato chooses two articles, separated by 20 years but closely connected by subject (the effects of phlorizin on glycaemia and insulin secretion) and ultimately by their potential to transform the treatment of diabetes:

Rossetti L, Shulman GI, Zawalich W, De Fronzo RA. Effect of Chronic Hyperglycemia on In Vivo Insulin Secretion in Partially Panceatectomized Rats. J Clin Invest. 1989 (Oct):80; 1037-1044. https://pubmed.ncbi.nlm.nih.gov/3308956/

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE. EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. NEJM. 2015 (Nov): 2117-2128. https://pubmed.ncbi.nlm.nih.gov/26378978/

Watch the first film in the ‘Gamechangers’ series, ‘New vision, new treatment’ presented by Professor Stefano Del Prato, launching this week on Horizons.

For more on this topic, enrol on the following EASD e-Learning course:

• SGLT-2 inhibitors

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

In his new module for EASD e-Learning, Professor Eelco de Koning considers the various options available for restoring normal glucose regulation by replacing insulin-producing cells – whether through islets or whole pancreas transplantation.

Eelco de Koning, Professor of Diabetology at Leiden University Medical Center, The Netherlands, is in no doubt about the challenges posed by diabetes self-management. “We should all realise that the insulin-producing cell is the perfect closed-loop system,” he says. “It measures glucose continuously. It provides the right signals to the secretory part of the insulin-producing cell, providing exactly the amount of insulin that is needed. The insulin will have its effect on glucose uptake, especially in muscle and fat tissue. And the lowering of glucose by increased glucose uptake will be detected by the glucose sensor. In our treatment of patients with severe beta cell failure, we try to mimic this sensory function and the secretory function of the cell as well as possible. But it is impossible to achieve a perfect mimicry of this. And therefore, chronic hyperglycaemia will always exist, even with the advanced hybrid closed-loop systems that are currently available. So the only real solution for completely normal glucose regulation without risk of hypoglycaemia is replacement of the insulin-producing cells. But how do we do that?”

This last point is the central question addressed by Eelco’s module. Several transplantation options are now available, including islet transplants, simultaneous pancreas-kidney transplants and pancreas transplantation alone. All carry risks – not least the necessity for immunosuppressive treatment for as long as the transplant endures. Whole pancreas options carry additional surgical risk, including bleeds, leaks and fistulas. Islet grafts will likely require more than one infusion of islets due to the high rate of beta cell mass-loss involved. All are constrained by availability of donor tissues.

Weighed against these are the benefits in terms of glycaemic control, risk of diabetes complications, long-term survival and quality of life. Of huge significance for many transplant recipients is the associated relief from hypoglycaemia – a benefit Eelco is keen to highlight, and spoke passionately to in his podcast on ‘The patient who changed the way I think about diabetes’. He describes the case of a middle-aged woman whose life had been seriously disrupted by repeated episodes of severe hypoglycaemia and loss of hypo awareness. “When we performed an islet transplantation it really transformed her life. She still needed a little bit of long-acting insulin, but still her life changed in a way that she was able to go out again, to go shopping, to interact with her friends, to have a social life. This example showed me what the impact of type 1 diabetes can be on patients that have to live with type 1 diabetes every minute of their life. And it also showed me the power of islet replacement therapy, the enormous impact that can have in a positive way on the lives of patients with type 1 diabetes.”

Eelco’s module ‘Pancreas and islet transplantation’ launches this week on the EASD e-Learning platform.

Don’t miss ‘Hypo impact’, Eelco’s contribution to our series The patient who changed the way I think about diabetes’, available on Horizons.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

The centrality of disrupted beta cell function to type 1 diabetes is widely understood. Less commonly appreciated is the vital part it plays in type 2 – a role that takes centre stage in Professor Hindrik Mulder’s new module.

In his module ‘Stimulus-secretion coupling in pancreatic beta cells’, the first in EASD e-Learning’s new course ‘Beta cell biology’, Professor Hindrik Mulder starts by addressing head on the significance of dysfunctional beta cells in the pathogenesis of type 2 diabetes.

“To develop type 2, it’s not sufficient to be insulin resistant. You can be as insulin resistant as you may and you will not develop diabetes – as long as your beta cells are strong and healthy enough to deliver the right amount of insulin, at the right time.”

What follows is a fascinating exploration of what we currently know about beta cell biology – focusing in particular on the complex intracellular triggering pathway by which healthy beta cells regulate blood glucose. Along the way, Hindrik examines the impact of recent innovations – including genome editing and stem cell research – which promise to revolutionise what is possible in beta cell biology research.

It’s a topic close to Hindrik’s heart. He has been actively researching in this field at Lund University, Sweden, for several years, developing metabolomics and imaging techniques to explore metabolic events in beta cells and islets. More recently he has elucidated how genetic variants associated with type 2 diabetes contribute to disease mechanisms.

Given the rarity of monogenic forms of type 2 diabetes and the multi-gene and multifactorial nature of the condition’s most frequent form, why should we pay attention to these genes? “I think it’s really important to understand how the disease develops,” Hindrik explains. “The more we learn, the better we understand it. But also, we can actually base treatment on understanding how these genes are implicated in the development of type 2 diabetes. It could be a pathway that we could perhaps affect by some drug. So it’s very helpful to the pharmaceutical industry that we have all this information about these genes that are involved in the development of the disease. These genes will help us to identify drug targets. And since diabetes is such a severe disease affecting so many people, it’s really important to find as many useful therapies as we possibly can.”

For more on this topic, including from Hindrik’s research colleagues at the Lund University Diabetes Centre, watch out for other modules in the Beta cell biology course, coming soon.

For more on the causes of type 2 diabetes, enrol on the following EASD e-Learning modules:

• Understanding the causes of type 2 diabetes and how to achieve remission, by Professor Roy Taylor
• Obesity and the pathogenesis and outcomes of type 2 diabetes, by Professor Naveed Sattar
• Insulin resistance, the metabolic syndrome and type 2 diabetes, by Professor Kåre Birkeland

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

For the latest in our series ‘The long and the short of it’, renowned psychologists with a specialism in diabetes, Professors Bill Polonsky (University of California, USA) and Frank Snoek (Amsterdam University Medical Center, Netherlands) discuss the psychosocial aspects of diabetes technology.

Recent decades have revolutionised what’s possible in diabetes self management with the arrival on the market of new technologies to support blood glucose monitoring and insulin delivery – or even to combine the two. But how far have these innovations actually benefited people with diabetes, not just in terms of their health outcomes but also their quality of life?

Between them, Professors Bill Polonsky and Frank Snoek have many years of active engagement with this topic – both as clinicians and as researchers. One thing they both agree on is the potentially transformative power of new technologies, in particular pumps, continuous glucose monitoring (CGM) and closed-loop systems. Says Bill: “From clinical experience I know that for many people with diabetes [these technologies] can bring an ‘Aha!’ moment. Certainly with sensor technology, it’s like someone turning a light on in a dark room. And that enthuses them about wanting to become more engaged with their diabetes care.”

Frank agrees, though he is careful to distinguish between his experiences as a clinician and as a researcher. Bill shares this observation. “As a clinician I’ve seen numerous examples of how it benefits people in their daily lives. As a researcher – not so much. So far, the research doesn’t show as much as we might hope.”

Quite why that may be, neither is sure, though they agree that it’s likely something to do with the way research is carried out, or how certain outcomes are measured. “A topic for a future discussion,” Frank suggests. What’s obvious, though, is the divergence in access to technology – which the two can testify is manifest both in the USA (where access is dictated by the patient having an insurer willing to pay) and in Europe, where national health systems have different approaches to reimbursement for such technology. For Frank this raises the troubling issue of inequality: “It’s worrying that technology actually increases the divide rather than closing that gap.”

The criteria according to which healthcare professionals deem people with diabetes to be suitable (or unsuitable) to have access to new diabetes technologies are also of concern to both. Frank explains that in the Netherlands, access to real-time CGM has been limited to those doing ‘poorly’ – with the result that people with better diabetes control are effectively punished by being denied access to technology that could improve their quality of life. In the USA, Bill points out, the bias has worked both ways. Access to CGM was initially limited to people with good control – therefore not available to people who needed it the most.

“There is implicit bias in these decisions about who gets access,” Frank says. “Its often based simply on healthcare professionals’ (HCPs) gut feelings about who might benefit. Ultimately, both hope the time will come soon when HCPS can ditch the inclusion criteria – stop thinking about people qualifying for technology and watch out instead for those people who are going to struggle with these technologies.

So what problems might be associated with diabetes technologies? Frank highlights the problem of perfectionism some people with diabetes may have. “Technology enables them to take that impulse even further – increasing the burden of living with diabetes.”

Bill agrees. “We sometimes see an obsessive-compulsive quality, and people in competition to achieve ‘great numbers’, seeking 100% time in range. Some people drive themselves nuts doing this. And put themselves at risk from hypoglycaemic problems as well.”

There are also problems relating to a lack of guidance and support in how to use the technology, and both argue that people need ‘problem-solving’ support for how to use these tools in order for them to really make a difference.”

Finally, HCPs need to be careful not to let the data generated by these technologies become another stick to beat their patients with. Says Frank: “they should be prepared to talk with their patients in a non-judgmental way about what these technologies reveal in terms of their behaviours.”

“There is so much blaming and shaming in diabetes,” says Bill. “It makes it very difficult for patients to stick with it.”

For more on this topic, see the following EASD e-Learning content:

• Do novel diabetes technologies really lighten the load?
  Professors Moshe Philip and Tadej Battelino
• Accessing new diabetes technologies: who decides – and how?

For more from Professor Frank Snoek, enrol on his module Fear of hypoglycaemia, module 3 of our Hypoglycaemia course.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

Patient education and support are crucial for effective diabetes management, right? So far, so uncontroversial – but what should that education encompass? Who should provide it, where and when? These are just some of the questions addressed in our latest module.

In his new module, An introduction to patient education in diabetes, which launches this week, Dr Joao Filipe Raposo traces the development of patient education in diabetes back to the earliest days of insulin treatment – in fact, almost to the moment insulin was first discovered by Banting and Best.

“Education and patient involvement were fundamental to achieving the benefits of insulin,” he points out. “For the first time in the history of medicine, patients had to be involved in their treatment and surveillance, since it was not possible to keep patients with a lifetime condition in hospitals, and with multiple daily injections of insulin. Since that time, in Canada, in the USA, in Portugal, patient education has been a requisite for healthcare providers.“

As well as being a professor at the NOVA Medical School in Lisbon, Dr Raposo is Clinical Director of Portugal’s Diabetes Association (the APDP) and President of the Portuguese Diabetes Society. He credits diabetes patient organisations such as these with much of the early advances in this field, citing the example of Ernesto Roma – the APDP’s founder. As an intern at the Massachusetts General Hospital, Dr Roma visited Joslin’s celebrated diabetes clinic in Boston, where Banting and Best sent the first vials of insulin in 1922. On his return to Lisbon in 1925, Roma set about introducing not just insulin therapy but education in the skills patients required to use it effectively – creating an educational department at the association that provided group lessons and individual tuition in nutrition, insulin administration and glucose monitoring.

It’s a story that was to be repeated many times over in the years after insulin therapy was first introduced (RD Lawrence and the British Diabetic Association is another example – see https://easd-elearning.org/exercise-and-insulin-a-powerful-combination/).

Times – and treatments – have changed considerably since then and Dr Raposo’s module is a valuable guide to the evolution of the tools and terminology employed in diabetes patient education over the years – including key concepts in disease models, behaviour change and self-care behaviours. The module also includes practical case studies highlighting the benefits of particular approaches to diabetes patient education, barriers to effective education and the role of technology in diabetes self-care and structured education.

For Dr Raposo’s new module, enrol on the EASD e-Learning course Patient education and support.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.

In the latest episode of The long and the short of it, professors Larry Fisher and Frank Snoek get to grips with some of the emotional aspects of living with diabetes – focusing on diabetes distress and depression.

One of the first points Professors Frank Snoek (Amsterdam University Medical Centre, Netherlands) and Larry Fisher (University of California, USA) make in their fascinating and wide-ranging discussion is just how important it is to understand the difference between diabetes-related distress and depression.

Diabetes distress, often linked to an overwhelming sense of powerlessness to control blood glucose and a fear of hyper- and (in particular) hypoglycaemia, is to be expected. As Larry says: “One would expect people living with this condition to have these experiences at some stage.”

His point is borne out in the statistics: around 35-45% of people with diabetes have elevated distress levels – a fact bemoaned by both professors given how easily distress can be addressed and reduced.

Depression on the other hand – “major depressive disorder or clinical depression, not just depressive symptoms; it’s a psychopathological diagnosis” – is much broader, affecting all aspects of life; tends to be episodic (whereas distress tends to be more chronic), and significantly has a lower prevalence relative to diabetes distress (estimated rates for depression in diabetes range between 4%-17%).

Clinical implications

Frank agrees that the distinction is crucial – and not only from a scientific point of view. “It also has important clinical implications for people with diabetes. It’s important to be able to tell people if the symptoms of distress that they are experiencing are ‘to be expected’. One of the things we do as clinicians and as psychologiests is to normalise these feelings. That can be a huge therapeutic intervention in itself.”

The distinction also has significant implications for how we approach diabetes-related psychological problems. “Only one in 20 people with diabetes distress also has clinically depressive symptoms,” Frank observes. “That’s an intriguing finding because it clearly demands us to think about the difference between these entities – anxiety, distress, depression, etc.

Larry reiterates the point: “They are not two sides of the same coin. They are very, very different. And that means very different clinical approaches – not only in terms of what to do about it, but who should be doing it and where those different interventions can occur.”

For instance, it’s important to get to grips with diabetes distress not just for the well-being and happiness of the patient – it may have an effect on other disease outcomes. Frank highlights that there is a stronger association between diabetes distress (much the more prevalent of the two conditions) and difficulty self managing than between depression and self management

What can be done?

The good news is that diabetes distress is extremely malleable and there are lots of things that can be done to help people overcome it.

‘Normalisation’ itself – reassuring people that the distress they are experiencing is normal – is one approach both Frank and Larry highlight. “Normalisation is an incredibly powerful and simple technique,” says Larry. ‘You don’t need to refer somebody to do that. That can be done in regular, traditional comprehensive diabetes care settings. Which suggests that maybe comprehensive care needs to include dealing with the emotional part of diabetes as well as glucose levels.”

What about other interventions? Can therapy reduce the problems people with diabetes distress experience with self-management? Based on his own clinical trial experience, Larry says yes, it can. “People who are distressed don’t have the bandwidth to adopt and process some of the interventions, such as diabetes education. It constrains energy, motivation and engagement. Once you begin to address the emotional portion of that, they become much more open. One of the striking things in our last trial  – which did not deal with management at all – was that there was a 20% increase in continuous glucose monitoring (CGM) adoption within the month following the intervention.”

But what about people with diabetes-related depression? “I find it reassuring,” says Frank, “to see that most of the approaches that have been shown to be relatively effective in depression in the general population are effective in people with diabetes. But we also know from our research that if you incorporate diabetes distress in your depression treatment, it becomes even more effective. And more acceptable to people.”

Incorporating diabetes into depression treatment will, however, require the involvement of psychologists or psychiatrists with diabetes knowledge – a combination, Larry cautions, that can be hard to find. As the two professors conclude, there’s still a lot of work to be done in this area.

Catch Larry and Frank’s full discussion in The long and the short of it, Diabetes distress and depression.

Pressed for time? Watch the short version of their presentation.

For more on the topics raised in this film, enrol on the following EASD e-Learning module:

• Fear of hypoglcyaemia, written and presented by Professor Frank Snoek.

(Module 3 in our Hypoglycaemia course.)

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.