One of the biggest drains on EU health budgets is largely preventable
By Pierre Meulien, IMI Director
Type 2 diabetes can wreak havoc on the body. It can affect everything from the kidneys and heart, to mental health, vision and even sleep. It can lead to blindness, stroke and amputations. To live well requires careful monitoring, and sufferers often have to accept a diminished quality of life. In addition to the immense personal burden, costs associated with treating diabetes and its complications put immense pressure on public health systems, totalling approximately 10% of healthcare budgets by the most recent WHO estimates.
Looking at risk factors in a new light
While there is certainly genetic susceptibility, environmental factors play a very significant part in a person’s likelihood of being struck down with type 2 diabetes (type 1 diabetes, on the other hand, is much more genetically determined). While we should investigate pharmacological interventions, the approach will have to be much more holistic. Prevention will be key. While most of IMI’s research projects so far have concentrated on the mechanisms and pathways of the disease, identifying subtypes, biomarkers and new animal and cellular models, we are also starting to look at it from angles related to behaviour, nutrition, exercise and even psychology.
One of our newer projects, SOPHIA, is trying to better understand obesity, one of the major risk factors for developing type 2 diabetes. The way we currently treat the disease is not working, according to SOPHIA researchers, and they want to change the way the medical community and society as a whole think about it and talk about it. The researchers want to move away from ineffective calorie-control and exercise treatments, and try to focus on treating the individual, rather than pursuing a broad-brush approach. Patients living with obesity will be included and consulted throughout the project.
Diabetes means different things to different people
As the disease manifests in different ways for different people, stratification, or grouping types of sufferers into subgroups, is a major research goal for IMI, as it will allow for personalised treatments.. We have dedicated significant resources to this task. To give some examples of success: in 2016, the DIRECT project led to the discovery biomarkers for blood sugar deterioration, and developed tests to predict who will get diabetes, whose condition will deteriorate rapidly after diagnosis, and who will respond well or badly to certain drugs. In 2018, two of our projects, BEAT-DKD and RHAPSODY combined measurements of biomarkers like insulin resistance, insulin secretion, blood sugar levels and age at onset of illness, that allowed them to distinguish five distinct clusters of type 2 diabetes patients from a cohort of nearly 14,000 newly-diagnosed patients. Before that, classification was only type 1 or type 2.
Overcoming research bottlenecks
Biomarkers can also help predict who is at risk for complications such as cardiovascular problems, or problems of the retina, kidneys, and nervous system. Researchers from SUMMIT discovered 14 biomarkers that can differentiate between patients who will rapidly develop end-stage kidney disease, which requires dialysis, and patients who are less likely to need dialysis in the near future. This work of identifying and validating biomarkers helps overcome the inherent difficulty in designing clinical trials for diabetes, a major research bottleneck. By definition, the trials have to be very large because of the size of the population affected. That makes it extremely challenging to decide what kind of endpoint to consider.
Another bottleneck in diabetes research was overcome by IMIDIA researchers, who managed to develop a human pancreatic beta cell line that behaves the same way in the lab as beta cells in the body. This allows future researchers from both industry and academia to substitute rodent beta cell lines, previously used in all diabetes-related research, and to standardise the screening of molecules. This saves not only time and resources but also the use of animals in research, which is very important for IMI.
More patient involvement, better technological solutions
While most of our diabetes research concerns type 2, we are also funding projects that will advance our understanding of type 1 diabetes. Researchers from INNODIA have identified molecules that trigger the immune system in people with the disease, and shed new light on the role of white blood cells and the thymus. They’ve also developed a clinical trial protocol that will make it easier and faster to launch trials for new drugs. We have just launched a follow-on project called INNODIA HARVEST that will continue the hunt for biomarkers and run two new clinical trials for potential new treatments, with patients and their families at the heart of the research all the way through.
Diabetes research is one field that will benefit enormously from being able to remotely-monitor different variables like glucose and other biomarkers, but also activity, nutrition, and psychosocial variables. This idea underpins the mission of the future partnership that will take the place of, and expand on, IMI2 in the coming years. As we, with our new partners, continue to innovate and incorporate new and better technological solutions, even more benefits for patients are likely to emerge in the years to come.