|Type 2 diabetes (T2DM) is preventable by sustained changes in diet and physical exercise. Despite this, modern societies are already approaching 10% population prevalence of diabetes, and another 15% with pre-diabetes. The costs of T2DM are huge, approaching 10% of all health costs. Prevention of diabetes is a priority for national healthcare agencies and for the health insurance industry. Investment in prevention and lifestyle programmes requires a solid evidence-base for targeting and customising these interventions in a cost-effective manner. Translation of the findings from T2DM prevention studies to the benefit of general public health has not yet been possible.DEXLIFE will identify novel diagnostic and predictive biomarkers (i) to detect the progression toward diabetes in high risk individuals and (ii) that are responsive to lifestyle interventions known to be effective in diabetes prevention. New biomarkers alone will be insufficient to alter the course of diabetes progression. We bring a strong translational focus to this proposal, by setting the main intervention in the real-life context of a major health insurance system. The accumulated phenotyping repertoire from an extensive panel of –omic analyses will be refined and modelled into a new diagnostic panel for the allocation of high risk subjects to individualised preventive regimens.Our multi-disciplinary team has a strong track record in clinical diabetes and metabolism. Several unique clinical cohorts will provide the basis for a series of clinical, physiological and mechanistic investigations, which will identify, monitor and analyse the impact of biomarkers over time. An exercise and dietary intervention study will be included in two specific cohorts, enabling us to assess the impact of such interventions on plasma biomarkers and functional tissue-based markers. Project clinical and industry partners will support the translation of our findings into clinical practice.