Diabetogenic action of statins — mechanisms and consequences. Review

Abstract

Over the past 20 years, the data according to the primary and secondary prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM 2), usually using predefined subgroup analyses, has consistently shown conclusive evidence of reduced relative and absolute risk of CVD. However, enthusiasm for using 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors has been significantly reduced by the results of follow up of patients in whom DM developed against the background of statins’ administration.The mechanisms by which statins may contribute to the DM 2 development have not been fully understood, but both targeted and non-targeted effects may be involved. These effects include: the effects on the mevalonate pathway, accompanied by inhibition of several pathways of cellular biosynthesis; activation of gluconeogenesis processes by increasing the expression of key enzyme genes; disruption of insulin signalling pathways; changes in circulating free fatty acids; hormones; functional and structural state of β-cells; maturation/differentiation of adipocytes. Additional mechanisms, particularly epigenetic regulation mediated by specific miRNAs (a class of short non-coding RNA molecules involved in the regulation of RNA translation and degradation), are also involved in the reduction of insulin secretion.Currently investigations are being conducted to elucidate the statin-induced mechanisms of DM 2 development. It has been established that therapy with HMG-CoA reductase inhibitors, although it affects the accession of DM 2, but helps to reduce the accession and/or progression of CVD. Therefore, statins should be continued in patients at high or very high risk of CVD to achieve the target levels of low-density lipoprotein cholesterol. Therefore, before starting treatment, it is necessary to assess the degree of risk. HbA1c and blood glucose levels should be monitored regularly in people at high risk for developing DM 2 who receive statins.