Mechanisms of prevention of type 2 diabetes by lifestyle intervention in subjects with pre-diabetes or at high risk for progression

DEXLIFE – FP7 EU-funded multidisciplinary diabetes prevention project

Aim and purpose
Large-scale diabetes prevention studies have clearly shown that type 2 diabetes can be prevented or delayed in people at high-risk by sustained changes in both diet and physical exercise. However, despite solid evidence for preventive actions, it remains a challenge to effectively identify and manage individuals in the general population who are at high risk of developing diabetes or those who already have undiagnosed diabetes.

Not only are there multiple patterns of progression towards diabetes, there is also a significant variation in individuals response to interventions on exercise and diet. Thus, even if people are accurately identified as having pre-diabetes, their subsequent response to preventive exercise intervention remains difficult to forecast and is still highly variable.

DEXLIFE is tackling these problems by identifying novel markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. These markers should ideally be sensitive to small changes in physiology and demonstrate change with deteriorating glucose tolerance as well as with improvements in glucose tolerance in response to lifestyle intervention. The identification of new biomarkers of this kind could facilitate a completely new approach to disease prevention, based on accurate prognostic phenotyping of high-risk subjects and accurate selection of these individuals for the appropriately matched interventions.

Design and method
The DEXLIFE project encompasses a uniquely broad and deep research population. This includes 4 cohorts and 1 intervention study. These include the METSIM (Metabolic Syndrome in Men) cohort (a longitudinal study following 10,197 men aged 45 to 73 from the city of Kuopio in Finland); the VHI Diabetes Mellitus and Vascular Health Initiative (DMVhi) cohort (The VHI screening study identified 700 participants out of the 30,000 VHI policy holders who participated in this first large-scale screening study); a YT2 (135 Young Type 2 participants were recruited from the outpatients clinics at St. James’ Hospital Dublin) cohort; and the longitudinal multicentre RISC cohort (1,500 Europeans, recruited in 2003 and followed-up in 2008 and 2013). The intervention study will comprise of 400 participants from Ireland who have a sedentary lifestyle and are deemed at higher risk for developing type 2 diabetes. This programme will help to determine if circulating and tissue biomarker metrics change along with physiological and clinical parameters. Novel biomarkers for the prediction of progression towards T2D will be sought following scientific analysis of samples from these studies.

Target group
The research project targets patients with type 2-diabetes and people at risk for developing type 2- diabetes.

Expected outcome

The greatest impact of the DEXLIFE project will be to prevent progression to diabetes in high-risk European citizens. This will happen, on a small scale, during the lifetime of our research project and on a larger scale following the dissemination and/or commercialisation of the project results. The prevalence of diabetes is reaching epidemic proportions, driven by modern trends in diet and physical inactivity. The associated treatment challenges are complex because diabetes is a major contributor to cardiovascular disease, blindness, non-traumatic amputation and kidney failure.

The impact of DEXLIFE will extend beyond European borders. Type 2 diabetes is now a global epidemic with the greatest rates of increase in Asia and developing countries. However, phenotypic characteristics of patients in these countries may differ from the typical pattern of patients from European countries. For example, BMI is significantly lower in Asian patients diagnosed with type 2 diabetes. Nonetheless, the underlying biochemistry and physiology are similar. What these countries most urgently require is an inexpensive, easy to administer, widely available screening test to identify high-risk individuals. The screening capabilities resulting from DEXLIFE can therefore benefit citizens that are at risk worldwide.

Funding and collaborators
DEXLIFE is an EU FP7 program with an EU contribution of 5,5 mio euros.
To achieve its aims, DEXLIFE brings together a multi-disciplinary team of experts in clinical diabetes, metabolism, *omic technologies and large-scale screening and intervention. This includes:

  • Steno Diabetes Center (clinical diabetes, project management, dissemination, exploitation)
  • DCU (exercise physiology, insulin resistance, community-based exercise interventions, interventions in high risk cohorts)
  • VHI (largest Irish health insurance company, first large-scale Irish diabetes screening programme)
  • IRB Barcelona (energy metabolism, cellular mechanisms of insulin resistance)
    • IDIBELL (epigenetics, development of new drugs)
  • VTT (metabolomics, systems biology)
  • UEF (diabetes risk and prevention)
  • Metabolon (metabolomics, mass spectrometry analysis technologies, insulin resistance diagnostics, diabetes prognostic, project management, dissemination, exploitation)
  • UNEW (type 2 diabetes, insulin resistance, diabetes genetics)
  • Pintail (project management, dissemination, exploitation) 

Sidst opdateret 16-02-2016

Responsible

John Nolan
CEO and Head of Steno Diabetes Center

Tanja Thybo
Project Manager