Diabetes mellitus as a risk factor for aortic stenosis: from new mechanisms to clinical implications

Aortic stenosis (AS) is a progressive disease, with no pharmacological treatment. The prevalence of diabetes mellitus (DM) among AS patients is higher than in the general population. DM significantly increases the risk of AS development and the rate of its progression from mild to severe. However, the mechanism of the interaction between AS and DM is not fully understood. Limited data regarding the influence of hyperglycemia on valvular calcification are available while understanding the cross-talk between them is pivotal in designing an effective therapeutic approach to prevent or at least retard AS development and/or progression in DM patients. Analysis of aortic stenotic valves revealed that increased accumulation of advanced glycoxidation end products (AGEs) was associated with enhanced valvular oxidative stress, inflammation, expression of coagulation factors and markers of calcification. Moreover, AGEs valvular expression correlated with AS severity. Interestingly, in diabetic AS patients, valvular inflammation correlated only with long-term glycemic control parameters, i.e. glycated hemoglobin and fructosamine but not with serum glucose levels. It has been demonstrated that transcatheter aortic valve replacement (TAVI) is beneficial for AS patients also with concomitant DM and safer as compared to surgical aortic valve replacement (SAVR). Moreover, new antidiabetic drugs, such as glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors, targeting inhibition of AGEs-mediated oxidative stress, have been proposed to reduce the risk of AS development in DM patients. This review aimed to comprehensively discuss the impact of DM on AS and its potential therapeutic implications.