Diabetes challenges of the 2020s

A sustainable society with equal care for all

The societal costs of diabetes are high, require large efforts from healthcare and affect the individual's work situation. People with diabetes have a greatly increased risk of several serious conditions such as heart attack, stroke, kidney failure, foot ulcers and visual impairment.

In diabetes, the risk of cardiovascular complications is particularly high if there are other concomitant risk factors, such as high blood pressure and high levels of blood fats. Type 2 diabetes, if community efforts are made, could in many cases be prevented by identifying and intervening in high-risk groups. Even when diabetes is diagnosed, improvement in the patient's lifestyle and support for self-care is a cornerstone of treatment. Obesity and physical inactivity are important risk factors for type 2 diabetes and also affect the effectiveness of treatment.

Joint efforts to improve diet and physical activity have a high potential to cost-effectively prevent illness and improve prognosis. Knowledge is needed on how new habits can best be stimulated and motivation is extremely important in the individuals affected by diabetes. Good communication between patients and healthcare professionals is an important aspect of care and can lead to increased knowledge and better outcomes of the disease. A major challenge is also to provide individuals with a mother tongue other than Swedish with full information and good care. Non-European immigrants are a high-risk group for diabetes, which is considered to be a consequence of exposure to diabetes-driving risk factors such as vulnerable socio-economics, unfavourable lifestyles, heredity and genetics. In this patient group, the metabolic control is poorer and the risk of complications is higher than in people born in Sweden. Language barriers and demands for translation in combination with a lack of knowledge to understand the importance of self-care further complicate the whole thing. Increased knowledge about cultural and structural barriers could lead to health economic gains for healthcare and not least to better health and quality of life for the individual.

At Uppsala University, there is research that addresses these issues, including a transnational perspective. The Center for Health Economics (HEFUU), a collaboration between Humsam and Medfarm, has great expertise in understanding the future social costs of diabetes and participates in the diabetes network. The Center for Medical Humanities and Social Sciences (CMHS), a collaboration between the faculties of history-philosophy and social sciences and Medfarm also constitute a platform for research and multidisciplinary dialogue on issues related to medicine and health.

A good life with type 1 diabetes – how can technological innovations contribute?

The medical treatment of diabetes aims to lower blood sugar to normal levels, but in many cases also carries risks of so-called hypoglycemia, too low blood sugar. It is a condition that can lead to death.

To limit the development of complications to the disease, as well as side effects of medication, there is a great need to develop new, more effective individualised drugs and technical systems for treatment support for patients.

With new technology such as automatic blood glucose meters connected to mobile apps and blood glucose-controlled insulin pumps ("artificial pancreas"), healthcare and patients with type 1 diabetes have been provided with advanced decision support. Today, just over a fifth of type 1 diabetes patients in Sweden have insulin pumps and the trend is that the insulin pumps are becoming an increasingly advanced type where they are combined with technology to measure blood sugar continuously. However, even patients who have had access to these advanced systems usually do not reach the national treatment goals but have harmful, chronically elevated blood sugar levels. Much of the responsibility for the treatment of type 1 diabetes remains with the patient, who makes daily decisions about the dosage of insulin, which is significantly affected by difficult-to-assess factors such as diet and lifestyle. Thus, there is still great potential for technological development to even better mimic the body's secretion of insulin and other blood sugar-regulating hormones such as glucagon, alternatively to develop regenerative therapies or cell therapies that replace destroyed beta cells.

In this context, it will be important to study the effect of technical interventions on cells and endocrine systems. Automatic systems for blood sugar regulation are rapidly evolving towards fully implantable solutions, which require new materials and design of components as well as new principles for communication between units inside and outside the body. Uppsala University has ongoing research regarding the improvement of sugar sensors and IT security in these sensitive systems. Furthermore, Uppsala University's strengths in microfluidics, nanotechnology and biomaterials apply to these issues.

Curing type 1 diabetes – is it possible?

Today, treatment for type 1 diabetes still focuses on lifelong insulin replacement therapy. In the future, cell therapies may provide the opportunity for curative treatment of patients, for example through treatment with stem cells into insulin-producing cells.

This challenge requires the understanding and development of bioprocesses for the safe and scalable manufacture of new biological drugs and cell therapies (so-called “advanced therapeutic medicinal products” (ATMP)) that are effective and safe for the individual and cost-effective for society.

The development is going at a furious pace and Sweden is a pioneering country with high technical competence and many actors who drive the development forward in combination with a strong patient group that pushes the development. In Uppsala, there are excellent conditions for leading the development in both medical technology and cell therapy in type 1 diabetes. At the University Hospital, there is an established Center of Excellence (CoE) in type-1 diabetes, which is a natural gathering place for clinical trials in the field and which can then also benefit from the University Hospital's centrally established support for clinical trials and close collaboration with Uppsala Clinical Research Center (UCR) as regulatory support. In addition, the University Hospital in collaboration with Uppsala University has a special investment in medical technology and innovation with the potential to further strengthen this competence.

Stop the infarction before it comes with an individualised type 2 diabetes treatment

For the treatment of type 2 diabetes, several new classes of drugs have been added in recent years. Some enhance insulin production by mimicking the body's own intestinal hormone, GLP1 and a group of drugs that increase sugar excretion in the urine, so-called SGLT2 inhibitors.

Both of these types of drugs have shown great benefits in addition to controlling blood sugar, such as reducing high blood pressure and obesity.

In addition, significant effects of these drugs have been found in protecting against cardiovascular and premature death in some patients with type 2 diabetes. At Uppsala University, there is extensive experience and several ongoing projects around these and other new treatments for type 2 diabetes.

Despite these advances, the disease is progressive with deterioration of self-insulin production and blood sugar control over time. Therefore, we need to better understand how humans' regulation of metabolism works, as well as the causes of hormonal changes, such as declining insulin production and increasing insulin resistance, during disease development.

New treatment strategies that are tailored to the individual, as well as the possibility of targeted treatment aimed at beta cells or insulin receptors in, for example, the liver, are important to develop, to achieve a more effective treatment in the future.

In Uppsala, there are many established cohorts and biobanks that make it possible to study individuals at risk for developing type 2 diabetes (such as PIVUS, SCAPIS and EpiHealth) and also a cohort of individuals who have developed diabetes (All new diabetics in Uppsala County; ANDIU). Most patients with type 2 diabetes are treated in Sweden in primary care. The equivalent of the Academic Hospital in primary care is Near Care and Health in the Uppsala Region (NVH), which is a separate university health care unit and as part of this has created an academic primary care centre with two academic care centres (AVC). AVC also has an assignment for the health centres run by private actors. NVH has recently chosen to prioritise efforts against diabetes and will in the spring of 2020 create an interprofessional network of employees in primary care health care who are interested in diabetes research. This constitutes a natural basis for collaboration on diabetes research also in primary care between an Uppsala Diabetes Centre and those active in the Uppsala region.

Can interdisciplinary science solve the diabetes mystery?

A major problem in diabetes research is that it is difficult to study the insulin-producing beta cells in living people in isolation. Taking a tissue sample of the pancreas involves risks for the patient. Studying tissue in patients with diabetes who have just died is a way forward and here the Rudbeck Laboratory at Uppsala University has been a pioneer in collecting tissue and extracting living cells as beta cells in the form of Langerhans cell islands. This provides unique opportunities to study in detail the physiology and pathophysiology of beta cells, as well as how beta cells interact with other cell types in the Langerhans islands such as glucagon-producing cells and support cells such as endothelium and macrophages.

Another method developed at Uppsala University is that, with the help of modern imaging, including functional imaging with the labelling of the beta cells, it is possible to follow how the amount of cells changes during diabetes development in both humans and animals. In the same way, it is possible to take "digital biopsies" of the body's organs with imaging to study important processes in the development of diabetes and its complications, such as studying immune cells, fibrosis, flow and insulin resistance.

Common to all these studies is that today we generate large amounts of data. In Uppsala, we have extensive experience of working with large amounts of data from registers and biobanks, and we have a high level of competence with opportunities to process its data further through advanced calculation methods to assess disease risk. Uppsala University offers an exceptionally good environment for the development of computer-aided technologies and methods. For example, an interdisciplinary medical technology centre, Medtech Science and Innovation, is in the start-up phase at the Department of Information Technology at Uppsala University. This centre is at the forefront in terms of e.g. mathematical modelling, machine learning and computerised image analysis and a professorship in artificial intelligence are under appointment.

Two national infrastructures for modern imaging have been placed at Uppsala University. An integrated PET/MRI (Positron Emission Tomography/Magnetic Resonance Imaging) camera for clinical research (funded by the Swedish Research Council) and the Preclinical PET-MRI Platform (funded by KAW and SciLifeLab). These platforms are located in strong research environments in various interdisciplinary constellations, such as the Centre for Image Analysis at the Faculty of Science and Technology, the Section for Radiology at the Department of Surgical Sciences at the Faculty of Medicine and the Department of Medicinal Chemistry at the Faculty of Pharmacy.