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Statin Use and Risk of Diabetes

Statin Use and Risk of Diabetes 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. Back to top Article Information Correspondence: Dr Zeliger, Department of Chemical Toxicology, Zeliger Chemical, Toxicological, and Environmental Research, 1270 Sacandaga Rd, West Charlton, NY 12010 (hiz@zeliger.com). Financial Disclosure: None reported. References 1. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med. 2012;172(2):144-15222231607PubMedGoogle ScholarCrossref 2. Joshi HT, Fakes MG, Serajuddin ATM. Differentiation of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors by their relative lipophilicity. Pharm Pharmacol Comm. 1999;5(4):269-271Google ScholarCrossref 3. Lee DH, Lee IK, Song K, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002. Diabetes Care. 2006;29(7):1638-164416801591PubMedGoogle ScholarCrossref 4. Ko KP, Min H, Ahn Y, et al. A prospective study investigating the association between environmental tobacco smoke exposure and the incidence of type 2 diabetes in never smokers. Ann Epidemiol. 2011;21(1):42-4721130368PubMedGoogle ScholarCrossref 5. Devlin AM, Ngai YF, Ronsley R, Panagiotopoulos C. Cardiometabolic risk and the MTHFR C677T variant in children treated with second-generation antipsychotics [published online January 24, 2012]. Transl Psychiatrydoi:10.1038/tp.2011.68Google Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Statin Use and Risk of Diabetes

Archives of Internal Medicine , Volume 172 (11) – Jun 11, 2012

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Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2012.1243
Publisher site
See Article on Publisher Site

Abstract

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. Back to top Article Information Correspondence: Dr Zeliger, Department of Chemical Toxicology, Zeliger Chemical, Toxicological, and Environmental Research, 1270 Sacandaga Rd, West Charlton, NY 12010 (hiz@zeliger.com). Financial Disclosure: None reported. References 1. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med. 2012;172(2):144-15222231607PubMedGoogle ScholarCrossref 2. Joshi HT, Fakes MG, Serajuddin ATM. Differentiation of 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors by their relative lipophilicity. Pharm Pharmacol Comm. 1999;5(4):269-271Google ScholarCrossref 3. Lee DH, Lee IK, Song K, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002. Diabetes Care. 2006;29(7):1638-164416801591PubMedGoogle ScholarCrossref 4. Ko KP, Min H, Ahn Y, et al. A prospective study investigating the association between environmental tobacco smoke exposure and the incidence of type 2 diabetes in never smokers. Ann Epidemiol. 2011;21(1):42-4721130368PubMedGoogle ScholarCrossref 5. Devlin AM, Ngai YF, Ronsley R, Panagiotopoulos C. Cardiometabolic risk and the MTHFR C677T variant in children treated with second-generation antipsychotics [published online January 24, 2012]. Transl Psychiatrydoi:10.1038/tp.2011.68Google Scholar

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jun 11, 2012

Keywords: statins,diabetes mellitus,diabetes mellitus, type 2

References