The Influence of Genetics and Epigenetics on the Diabetes

Coordinators:

Annette Schürmann | Johannes Beckers | Martin Hrabě de Angelis

The (Epi)Genetics Academy has made significant progress in understanding the molecular causes of T2D and metabolic disorders. The successful transfer of research results from model systems to human cohorts has made it possible to identify central mechanisms that contribute to the development of the disease. These findings create a solid basis for the development of improved strategies for early diagnosis, individual risk assessment and targeted intervention – with the aim of sustainably optimizing care along the entire course of the disease.

Using functional genomics and mouse models, the Academy identified 17 new genes involved in obesity, MASLD and type 2 diabetes. Among other things, they influence fat cells, liver metabolism and the function of the islets of Langerhans. Their relevance has been confirmed in animal and human tissue, thus forming an important basis for new therapeutic targets. 

Genetic factors also have an influence on complications of T2D such as cardiovascular disease: The insulin regulator TBC1D4 not only increases muscle insulin resistance, but also heart damage post ischemia (vasoconstriction or vascular occlusion). This underlines insulin resistance as a controllable risk factor in diabetes-related heart failure.

DZD researchers analyzed blood samples from over 1700 people and found certain lipids and amino acids that are associated with obesity and T2D. The fat molecules sphingomyelin and phosphatidylcholine in particular could explain how obesity increases the risk of diabetes. Genetic analyses and animal experiments confirm that changes in fat metabolism play a central role in the early development of the disease.