Actionability of Genetic Variants in Diabetes: Core Aspects and Applied Examples Free

Diabetes is a complex and highly heterogeneous disease, and its traditional division into broad diagnostic categories such as type 1 diabetes and type 2 diabetes fails to capture its underlying pathology, which can lead to diagnostic misclassification and suboptimal treatment. Growing evidence of the genetic components of diabetes, combined with advancements in and availability of genomic technologies, have created high expectations for precision medicine in the field of diabetes, which have yet to be met. Successfully implementing genomic precision medicine in the clinical setting requires bridging the translational gap between research and practice. At the core of this effort lies the concept of actionability, which lacks a clear, cross-disciplinary definition and robust and broadly accepted criteria to assess when and in which contexts a genetic variant is actionable. This work is a collaborative effort between philosophy of medicine and biomedical science disciplines that seeks to provide a framework to assess the actionability of genetic variants in the treatment and management of diabetes. Building on the scientific, medical, and philosophical literature and using an example case study, the authors describe core aspects of actionability and evaluate the tensions between research and practice, diagnosis and discovery, and clinical actionability and relevance.