Differential metabolic effects of distinct statins Atherosclerosis, 03/25/2011

Koh KK et al. – The authors discuss the differential effects of statins on metabolic homeostasis and insulin sensitivity.

• Reciprocal relationships between endothelial dysfunction and insulin resistance suggest that therapies improving endothelial dysfunction will simultaneously improve insulin sensitivity and other metabolic parameters.
• Previous studies with some statins either did not alter insulin sensitivity or promoted insulin resistance despite significant improvements in endothelial dysfunction and decreases in circulating pro-inflammatory markers.
• This may be due to pleiotropic or off-target effects of some statins to cause insulin resistance by diverse mechanisms unrelated to endothelial dysfunction.
• There is evidence of other differential metabolic actions of distinct statins including effects on hydroxymethylglutaryl-CoA reductase inhibition, isoprotenoid synthesis, calcium release, glucose transport, insulin secretion, and/or insulin resistance.
• Pravastatin increases expression of adiponectin mRNA, enhances adiponectin secretion, increases plasma levels of adiponectin, and enhances insulin sensitivity in humans.
• Clinical studies including large scale randomized controlled trials demonstrate potential differences between individual statins, with pravastatin promoting risk reduction for new onset of diabetes.
• Conversely, other statins including atorvastatin, rosuvastatin, and simvastatin all promote significant increase in this risk.
• Given the frequent concordance of metabolic diseases including diabetes, obesity, and metabolic syndrome with cardiovascular diseases associated with hyperlipidemia, it is important to understand the potential metabolic risks and benefits of therapies with distinct statins.