The diabetogenic action of statins — mechanisms and clinical implications

Abstract

Treatment with statins has transformed primary and secondary prevention of cardiovascular disease (CVD), including thrombotic stroke. Evidence-based data demonstrate the benefits and safety of statin therapy and help to guide clinicians in the management of populations at high risk of CVD. Nevertheless, clinical trials, meta-analyses and observational studies highlight a 10-12% increase in new-onset diabetes mellitus (NODM) among patients receiving statins. The risk further increases with intensive therapy and among individuals with known risk factors for NODM. Mechanisms underpinning this effect are not yet fully understood; however, Mendelian randomization studies suggest that they are related to lowered activity of HMG-CoA reductase, the target of statin therapy. In vitro research indicates that statins potentially impair β-cell function and decrease insulin sensitivity but how these findings relate to patients is unknown. In the clinic, statins should be prescribed on the basis of CVD risk and individual patient characteristics. In addition, diet and lifestyle interventions should be emphasized to help mitigate the risk of NODM. Individuals who develop NODM while taking statins do not exhibit increased microvascular disease, which is reassuring. In diabetes mellitus of long duration, the effect of statins on glycaemic control is small and unlikely to be clinically important.

Simvastatin and Atorvastatin inhibit DNA replication licensing factor MCM7 and effectively suppress RB-deficient tumors growth

“…Statins, inhibitors of HMG-CoA reductase and well-known cholesterol-lowering drugs, have been used in clinic for almost 40 years and have been proved to be safe, effective drugs with minor side effects. 43, 44, 45 Randomized controlled clinical trials have indicated that statins have provocative and unexpected benefits for reducing the incidence of colorectal cancer and melanoma. 46, 47, 48 Statins can also inhibit tumor growth via different mechanisms, such as inhibition of angiogensis or inflammation.…”

“…No evidence shows that statins result in tumor; instead randomized controlled clinical trials indicate that statins have unexpected benefits of reducing tumors. 43-45 …”

Associations of statins and antiretroviral drugs with the onset of type 2 diabetes among HIV-1-infected patients

“…In contrast, a study of the HOPS cohort [18] reported a 14% increase in the incidence of DM for each year of statin use, although the authors did not specifically analyze the association between statin dose and DM occurrence. However, as the cardiovascular benefits of high-dose statin use outweigh the potential risk of developing DM [23], it may be advisable to regularly monitor for changes blood glucose and glycated hemoglobin levels in patients who are receiving high-dose statins and have a high risk of developing DM.…”

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

“…109,110 Getting back to the cardiovascular protective effect of statins, a controversy exists due to the observations that statin therapy has been associated with a 10-12% increased risk of developing diabetes. 111 A meta-analysis showed that statin therapy is associated with a 9% increase risk for diabetes; however, authors conclude that the benefits of statin therapy outweighed the risks. 112 Indeed, hyperglycemia produces endothelial dysfunction, a key determinant of diabetic micro-and macro-angiopathy, and statins could be beneficial in both conditions due to pleiotropic effects of this particular class of drugs.…”