There are an estimated 420 million people worldwide suffering from diabetes, and that figure is set to rise to 700 million by 2025. Many diabetes patients develop devastating, chronic complications including coronary heart disease, stroke and peripheral vascular disease, as well as eye and kidney problems. These complications impose an immense burden on the quality of life of the patients and account for more than ten percent of the health care costs in Europe.
Currently there is a high therapeutic need for new treatments for diabetes complications beyond the existing diabetes treatments, which focus mostly on lowering blood glucose levels. Clinical trials to show the benefits of potential therapies are lengthy and costly. Therefore, the key objective of SUMMIT was to develop procedures, technologies and tools to make clinical trials to test novel medications for diabetes complications shorter and more focused.
Clues in patients’ blood
Not all patients are at equal risk of developing diabetic complications. In order to better predict, monitor and treat the patients at risk, the scientists of the SUMMIT project searched for biological clues (biomarkers) in the patients’ blood and urine that indicate if a patient is likely to develop complications. As part of the analysis, researchers measured almost 2 000 biomarkers, and identified some important predictors for diabetes complications. For example, they discovered a panel of 14 biomarkers which can differentiate between patients who will rapidly develop end-stage renal (kidney) disease, which requires dialysis, and patients who are less likely to need dialysis in the near future. A patent has been filed for this panel of biomarkers, and could become a valuable tool for doctors and hospitals in evaluating their patients and predicting their future treatment needs.
When it comes to the cardiovascular disease, the scientists also discovered a panel of six biomarkers which improve our ability to predict which patients will develop cardiovascular disease. They also found that an enzyme which softens the plaque that builds up in blood vessels is a risk factor in developing cardiovascular disease. If this enzyme is active it leads to plaque rupture, which in turn leads to a heart attack or a stroke.
Looking for answers in the genes
In addition to the biomarkers, SUMMIT scientists performed large examinations of genetic variants in different individuals to see if any variants are associated with a higher risk of developing diabetes complications. These studies were performed on almost 11 000 patients for kidney disease, more than 24 000 patients for cardiovascular disease, nearly 10 000 patients for retinopathy (a common eye disorder in diabetes patients) and more than 17 000 patients for lower extremity arterial disease. The comprehensive analysis – the largest such effort undertaken to date – showed that there are no obvious genetic markers which predispose patients to developing diabetes complications. The huge collection of genetic data which was generated during this effort will be a valuable asset in further research.
Of mice, rats and men
In order to improve preclinical trials, the SUMMIT team also performed a systematic review of 19 existing and newly generated animal models for diabetes complications. Such an effort had never been done before, and it helped clean up and clarify the situation in the field. A promising new rat model was developed, validated and a patent application for it has been filed.
Imaging and a new tool for predicting heart attacks and strokes
As part of its effort to improve imaging techniques to monitor the progress of atherosclerosis (the build-up of plaques in the blood vessels), the project has also developed a new, non-invasive ultrasound device capable of identifying patients at imminent risk of a heart attack or stroke. Although the device was developed for diabetes patients, it is now being validated for a range of other diseases. A patent application is pending and a start-up company, Mediscienta, has been created to develop this innovation commercially.
In addition to the work on biomarkers, genetic markers, imaging and animal models, the project recorded a number of other achievements.
- Scientists in the project completed a multi-centre study of diabetic cardiovascular patients, and created a database and a biobank with one of the best characterised diabetic cardiovascular patient groups in the world. Both will be an asset in future research.
- With 1 320 study subjects, the project created the largest dataset of optical coherence tomography (OCT) measurements in diabetes patents. OCT is a technique for obtaining images of the inside of the body at much higher resolution than other imaging modalities such as MRI or ultrasound. The project also developed a method to standardise OCT measurements in multi-centre trials and clinical practice.
- The project generated more than 100 scientific publications, with more publications still to come. It also resulted in 15 doctoral theses from different universities.
For the benefit of industry, academia and patients
Tools and techniques developed during this project, such as new biomarkers and imaging modalities, will improve the prediction of major diabetes complications in clinical trials. New animal models developed will make it easier to choose the right models for specific research questions in preclinical trials. All this will make drug development faster and more efficient, benefitting both the pharmaceutical industry and patients.
The academic community also reaped many benefits, such as access to the resources, expertise and knowledge of the pharmaceutical industry. Additionally, the project has opened up many new funding opportunities and new avenues for future collaborations between industry and academia.
Last but not least, SUMMIT raised the profile of the European research community globally; before SUMMIT, the diabetes research field was dominated by US consortia, but now Europe is increasingly seen as the leader in the field.
What happens next?
SUMMIT generated a lot of data and opened up many avenues for future research. Two new IMI projects, BEAT-DKD and RHAPSODY, will build on the legacy of SUMMIT to further advance research in the diabetes field in coming years.