Development of a systems biomedicine approach for risk identification, prevention and treatment of type 2 diabetes.

Type 2 diabetes (T2D) is a major public health problem, affecting more than 415 million individuals worldwide. In Europe, 60 million citizens suffer from diabetes and an additional 66 million have impaired glucose tolerance, causing 630,000 deaths each year. By 2030 the European prevalence of T2D is projected to reach 150 million, meaning that every 5th European will have diabetes or impaired glucose tolerance. As a result, around 28% of European healthcare budgets are assigned to diabetes care, costing at least 78 billion Euros a year. T2D is a multifactorial disease with many contributing risk factors, including age, obesity and a family history of diabetes.

T2DSystems is a translational project with the primary objective of bridging the gap between in vitro human islet studies and clinical studies in human subjects. The aim is to integrate cellular and medical research data, collected by the partners, with computational modelling. This will allow us to identify the complex pathophysiological mechanisms and markers of a spectrum of biological and cellular processes involved in pancreatic beta cell failure leading to impaired glucose tolerance and T2D. Mathematical models and networks of functional associations will be employed to understand how the different specific mechanisms and their correlations are related to the different forms of disease predisposition, onset and progression. This knowledge will be used to stratify patient-specific treatments in well-phenotyped patient cohorts. A new system-level description (including feedbacks of the endocrine system) of T2D is a prerequisite for the development of precision medicine. While patients and different patient cohorts may differ quite profoundly from one another, our integrative approach will allow us to infer shared mechanistic underpinnings as well as the features that stratify patients. Understanding patient-specific disease mechanisms through data integration and mechanistic modelling will help to identify new avenues for preserving normal glucose tolerance in groups of individuals with varying risks for T2D. As such, T2DSystems will help to develop ‘P3 medicine’: healthcare that is predictive, preventive and personalised.

The T2DSystems consortium has the following specific objectives:

  • To compile and expand existing human islet biobanks and datasets from the major European islet research centres, thereby creating the Translational human pancreatic Islet Genotype tissue-Expression Resource (TIGER)

  • TIGER will contain genetic, functional genomic, epigenomic, transcriptomic, proteomic and metabolomic human islet data from more than 1400 subjects with a broad spectrum of age, sex, genome-wide genotypes and glucose tolerance. TIGER will represent a unique T2D systems biomedicine relational resource that will combine clinical, genetic and molecular data at an unprecedented scale. This holds the promise to change the map of T2D research and diabetes research in general. It will be available to the T2DSystems partners by month 18 and will be publicly accessible to the research community by month 36 of the project.

  • To develop powerful large-scale data fusion and analysis tools to exploit TIGER data towards system-level biological insight