Precision therapy of type 2 diabetes

Type 2 diabetes (T2D) is an escalating health problem of enormous proportions. Clinical guidelines emphasise the need for personalized treatment to stop disease progression.

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 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 combining cellular mechanistic studies, animal investigations and clinical intervention data with a view to enabling new personalized strategies to prevent and treat T2D more effectively than today.First, we will study how treatment response to existing drugs is influenced by pathophysiological and metagenomic features.

Second, we will expand on our recent demonstration that beta-cells dedifferentiate in T2D and define the functional and gene expression changes that cause beta-cell failure.

These mechanistic insights will be used to identify new targets for beta-cell preservation, which is essential to stop disease deterioration, in particular in patients with poor insulin secretion.

Third, we will study how disease progression can be prevented by tailored early intervention with sulforaphane.The proposed studies break new ground and have the potential to both advance our understanding of the disease mechanisms of T2D and open up more precise treatment.