title: Are statins diabetogenic?
abstract: OBJECTIVE
  Statins are widely utilized for low-density lipoprotein lowering and for prevention of atherosclerotic cardiovascular disease. Although these drugs have a good safety record, increased risk of developing diabetes during extended use has recently garnered attention. Here we review clinical trial evidence related to statin use and incident diabetes, and the potential mechanisms for this association.
  
  
  RESULTS
  The increased incidence of diabetes with rosuvastatin treatment in Justification for the Use of Statins in Primary Prevention: an intervention Trial Evaluating Rosuvastatin (JUPITER) reignited attention on the link between statin therapy and diabetes. The JUPITER findings are supported by two recent meta-analyses of large-scale placebo-controlled and standard care-controlled trials, which, respectively, observed a 9% [odds ratio 1.09; 95% confidence interval (CI) 1.02-1.17] and 13% (risk ratio 1.13; 95% CI 1.03-1.23) increased risk for incident diabetes associated with statin therapy. However, the underlying mechanisms for this association remain unclear. Experimental evidence supports a paradigm implicating inhibition of β-cell glucose transporters, delayed ATP production, pro-inflammatory and oxidative β-cell effects of plasma-derived cholesterol, inhibition of calcium channel-dependent insulin secretion, and β-cell apoptosis.
  
  
  CONCLUSIONS
  The aggregate of large clinical trials supports the notion that statins modestly increase the risk of incident diabetes. Because diabetes is a risk equivalent condition for coronary and peripheral arterial diseases, these findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes while representing the strongest cardiovascular risk reduction tool in diabetics. We simply recommend regular glucose monitoring in patients taking statins.
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6300, USA. u.sampson@vanderbilt.edu
authors.forename: Uchechukwu K
authors.initials: UK
authors.lastname: Sampson
authors.forename: Macrae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control; D003920:Diabetes Mellitus / Q000139:chemically induced*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors