Reprogramming of cellular metabolism is emerging as a fundamental characteristic of many chronic diseases, including both type 2 diabetes and cancer. In studying metabolic reprogramming of skeletal muscle in type 2 diabetes, we have identified a link between nutrient excess, metabolic reprograming and cell survival that involves a class IIa histone deacetylase-p53 signalling axis. Phenotypically, this adaptive response shares many characteristics with cancer. We have used transcriptomic studies to predict a role for this signalling axis in breast cancer. Manipulating class IIa HDAC expression in breast cancer cell lines has uncovered metabolic vulnerabilities that we are attempting to target with both novel and common diabetes drugs.