The mineralocorticoid receptor: a new chapter for therapeutic regulation of diabetic cardiomyopathy

Abstract

Diabetes mellitus is a global health burden and represents a major cause of cardiovascular disease-related morbidity and mortality. Diabetic cardiomyopathy continues to predispose individuals to overt heart failure despite significant advances in the development of anti-hyperglycaemic medications. Currently, there is a lack of biomarkers for the detection of myocardial injury in the early stages of diabetic cardiomyopathy, which underscores the urgent need to identify early disease processes and develop novel therapeutic strategies. The mineralocorticoid receptor (MR) has proven to be a valuable therapeutic target in heart failure, which may translate to a promising option to reduce the risk of cardiovascular complications in mid-to-late stages of diabetic cardiomyopathy. This narrative review discusses the role of inappropriate MR activation in common pathogenic mechanisms underlying diabetic cardiomyopathy, as well as highlighting the circadian clock as an emerging target in diabetes that has been linked to modulation of MR activation. It will also outline the cardiovascular protection yielded from anti-diabetic agents and MR antagonists (MRA) in preclinical and clinical settings of diabetes. Although our knowledge of the mechanisms of myocardial injury in diabetes is expanding quickly, current therapeutic strategies do not mitigate the high risks of cardiovascular disease in this vulnerable population. Further investment in understanding the consequences of adverse MR signalling and potentially the early introduction of MR blockade in management plans may be critical for combating the burden of cardiomyopathy in the diabetic population.