title: 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.
authors.affiliation: Department of Diabetes &Endocrinology, University College Hospitals Trust, 3rd Floor Central, 250 Euston Road, London NW1 2PQ, UK.
authors.forename: D John
authors.initials: DJ
authors.lastname: Betteridge
authors.affiliation: Department of Medicine, University of Valencia, Avenida Blasco Ibañez, 17, 46010 Valencia, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control; D005247:Feeding Behavior; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D066298:In Vitro Techniques; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects; D057182:Mendelian Randomization Analysis; D012307:Risk Factors; D040242:Risk Reduction Behavior; D055502:Secondary Prevention
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006903:Hydroxymethylglutaryl CoA Reductases