Epigenetics for precision medicine and future therapies in type 2 diabetes

During 17-years, we have studied if epigenetics affect type 2 diabetes (T2D). We identified epigenetic changes (DNA methylation) in tissues from T2D patients versus controls. But the exact epigenetic modifications that cause T2D remain unknown.

A drawback with current epigenetic studies is that they have been done in whole human tissues containing many cell types, although epigenetics control cell specific expression. Hence, new studies on individual cell types should be done.

Most epigenetic T2D case-control studies have analyzed DNA methylation and no large studies have analyzed histone modifications. Since many T2D patients do not respond to current therapies, new treatments are needed. We will:1.

Study the impact of T2D, and its risk factors, on epigenetics (histone modifications) in individual cell types of human islets, muscle, fat and liver by novel experimental and machine learning methods.2.

Do functional experiments in cells and animals to test if identified epigenetic modifications associated with T2D cause T2D-related phenotypes. We will use epigenetic editing.3. Study if key epigenetic modifications found in aim 1-2 can be targeted for T2D therapies. We will test if inhibitors of epigenetic enzymes may affect insulin secretion and T2D.4.

Test if blood-based epigenetic biomarkers can be used for precision medicine in T2D. We will analyze DNA methylation in large prospective cohorts. We expect to open up new horizons for treatment and precision medicine of T2D.