Glycaemic variability identified as a critical determinant of myocyte dysfunction and risk for myocardial injury in preclinical models of diabetes

This study evaluates mechanisms of glycaemic stress underpinning cardiovascular risk in diabetes. Using in vitro and in vivo models, we demonstrate that glycaemic variability rather than hyperglycaemia alone is a dominant risk factor for heart muscle dysfunction and myocardial injury sensitivity in diabetes. These findings provide new preclinical models for mechanistic and drug discovery studies and inform strategies for managing cardiovascular outcomes in patients with diabetes. Overall design: hiPSC-CMs cultured in backbone media conditions or underwent constant and variable glycaemic stress disease modelling, and cells were harvested for RNA preparation and genome-wide RNA sequencing.