Pathogenetic mechanisms of statin dysglycemia and risk of new-onset diabetes

Abstract

Statins are the cornerstone for primary and secondary prevention of cardiovascular disease as they have been proven to reduce cardiovascular morbidity and mortality. Statins act by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, the rate limiting enzyme of cholesterol synthesis. Despite their important role in prevention of cardiovascular disease, there is evidence suggesting that they worsen glycaemia increasing the risk of type 2 diabetes by 10–12%, an effect that appears to differ by dose and type of statin used, with higher doses related to higher risk. Statins may cause hyperglycaemia through many pathways e.g., by increasing the intracellular concentration of calcium in the β-cell, leading to a decrease in insulin release and in addition may decrease the GLUT-4 transporter hindering the peripheral uptake of glucose. Diabetes is a major risk factor for cardiovascular disease, with statins offering remarkable protection, a property which should be stressed to the patient and perhaps even to healthcare personnel when hesitant to prescribe statins.