Statin Therapy and New-onset Diabetes: Molecular Mechanisms and Clinical Relevance

Abstract

Despite positive effects on the plasma lipid profile and vascular events, statin use is associated with various side effects. Among these, statins might cause a disruption of a number of regulatory pathways including insulin signaling. This may affect insulin sensitivity, pancreatic beta-cell function and adipokine secretion. The statin-associated risk of new-onset diabetes (NOD) appears to be a dose-dependent class effect. It still remains unclear whether statin treatment is associated with increased risk of NOD in the general population or if there are groups of individuals at particular risk. However, according to the available data it seems that cardiovascular (CV) benefits in high-risk individuals strongly favor statin therapy since it outweighs other risks. Whether statins should be used for primary prevention among patients with a relatively low baseline CV risk is still questionable, however the results of primary prevention trials have shown reductions in mortality in this population. Thus, there is a need for randomized, placebo-controlled statin studies with carefully selected groups of patients and NOD as a key end point in order to resolve queries concerning this issue.

Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

“…At least few mechanisms may contribute to causing NOD associated with statin therapy [34]. In recent years there has been a debate regarding the clinical implications of this phenomenon -whether and when we should start treatment, in what groups we should continue, stop it, or reduce the statin dose, and which groups of patients are at the highest risk of NOD [33,35].…”

STATINS-Do We Know Them or Are We Alice in Wonderland?

“…Rather, it advises doctors to monitor the blood sugar levels of their patients who take these drugs. The diabetogenic effects of statins are thought to arise from several mechanisms that converge on glucose regulation and pancreatic beta cells [2][3][4][5][6][7][8]9]. Including inhibition of isoprenoid synthesis and subsequent inhibition of glucose uptake by beta cells, increased uptake of LDL leading to glucokinase inhibition (hence blocking glucose conversion to pyruvate), and cytokine-induced overproduction of nitric oxide (NO) leading to beta cell apoptosis.…”

Statins-the Most Controversial Drug of Our Times: A Commentary

“…(8)(9) including inhibition of isoprenoid synthesis and subsequent inhibition of glucose uptake by beta cells, increased uptake of LDL leading to glucokinase inhibition (hence blocking glucose conversion to pyruvate), and cytokine-induced overproduction of nitric oxide (NO) leading to beta cell apoptosis. In addition, statins suppress ubiquinone and ATP synthesis.The ultimate effect of all these is the suppression of insulin production.Large no of studies have eventually reported that the as compared to the placebo group a greater no of patients eventually receiving statins therapy were subsequently diagnosed with Diabetes.…”