Author Affiliation: Department of Chemical Toxicology, Zeliger Chemical, Toxicological, and Environmental Research, West Charlton, New York.
The findings reported by Culver et al1 on the association between the risk of diabetes mellitus (DM) and the use of all types of statins suggest that a common mechanism for this causative effect exists. Although the 5 statins reported on (lovastatin, simvastatin, fluvastatin, atorvastatin, and pravastatin) differ significantly from each other in many ways, all share 1 common trait—all are lipophilic species.2 A strong dose-response relationship between serum concentrations of lipophilic persistent organic pollutants (POPs), including organochlorine pesticides, polychlorinated biphenyls, dioxins, furans, and polybrominated biphenyl ethers, and diabetes has been reported.3 Increased DM prevalence has also been reported for those exposed to other lipophilic chemicals including environmental tobacco smoke.4 Could the lipophilic statins be behaving in a mechanistic manner similar to these other lipophilic exogenous chemicals in acting to increase the risk of DM? Though statins are not as long lived in the body as POPs, an individual taking statins on a regular basis can effectively establish a steady-state level of these lipophilic species in his or her serum that can function in a manner similar to POPs and other lipophilic chemicals. A significant association between regular use of lipophilic pharmaceuticals and metabolic impact has been reported in populations other than the postmenopausal women described by Culver et al.1 A just-published article reports a high prevalence of metabolic syndrome in children treated with lipophilic second-generation antipsychotics.5 These findings suggest that the association between statin use and DM may be due to the lipophilicity of the statins. Notably, the only hydrophilic statin, cerivastatin,2 was not part of the reported study.
Zeliger H. Statin Use and Risk of Diabetes. Arch Intern Med. 2012;172(11):896–897. doi:10.1001/archinternmed.2012.1243