TRANSLATIONAL SIGNED

Project "TRANSLATIONAL" data sheet

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 Project objective

Type 2 diabetes (T2D) is an escalating health problem of enormous proportions. Current treatment strategies are unable to stop disease progression and prevent the devastating complications. Clinical guidelines emphasise the need for personalized treatment. However, this is currently implemented on trial-and-error fashion. We have recently found that T2D patients can be divided into four clusters, each with different characteristics. This represents a major step forward by pointing out the high variability of the pathophysiology and leads us to propose that anti-diabetic treatment should ideally target the underlying pathophysiology of each patient. The overall goal is to test this proposition by targeting existing and new treatment to patients who are archetypes of the two most severe T2D clusters, characterised by poor insulin secretion and pronounced insulin resistance, respectively. As a starting point, we will study how treatment response to existing drugs is influenced by pathophysiological features and also the gut microbiota. Next, we will expand on our recent demonstration that b-cells dedifferentiate in T2D and define the functional and gene expression changes that cause secretory failure. These mechanistic insights will be used to identify new targets for b-cell preservation, which is essential to stop disease progression, in particular in patients with poor secretion. Finally, we will study new compounds for tailored treatment, including sulforaphane as an early intervention for those with severe insulin resistance. My combined training in cell-physiology, bioinformatics and clinical medicine is unusual but necessary to conduct this multi-disciplinary programme. Whilst the programme builds firmly on my past research, it extends far beyond what I have attempted previously by exploiting novel state-of-the-art methodology to address central metabolic questions of high relevance to understand the causes, management and – ultimately – prevention of diabetes.