Author + information
- Kwang Kon Koh, MD, PhD⁎ ( and )
- Michael J. Quon, MD, PhD
- ↵⁎Division of Cardiology, Gachon University, Gil Medical Center, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, South Korea
We thank Dr. Mehta for commenting on our study (1). We agree that it is of significant clinical interest to understand potential mechanisms by which some statins have detrimental effects on glucose homeostasis whereas other statins improve the metabolic phenotype. Sukhija et al. (2) suggested that statins alter glycemic control by decreasing various isoprenoids that enhance glucose uptake via glucose transporter type 4 in adipocytes and contribute to insulin release.
Recent experimental studies have demonstrated that compared with hydrophilic statins, lipophilic statins have pleiotropic actions that cause unfavorable metabolic effects, such as reduction of insulin secretion and exacerbation of insulin resistance (3,4). Sattar et al. (5) showed that risk for the development of diabetes with statins is highest in older participants, while trials with pravastatin have reduced the development of diabetes in participants below a mean age of 65 years. We previously observed that pravastatin improves insulin sensitivity, whereas simvastatin worsens insulin resistance despite comparable improvements in lipid profiles and endothelium-dependent vasodilation in patients with hypercholesterolemia (6). These differential metabolic actions of lipophilic and hydrophilic statins are consistent with recent meta-analyses (7). Among plausible mechanisms that deserve further investigation are potential central nervous system actions of lipophilic statins to impair glucose homeostasis.
Certainly, mechanisms by which atorvastatin treatment results in increased fasting insulin and glycated hemoglobin levels require further investigation. Our observations are consistent with analyses of atorvastatin therapy and the incidence of diabetes (8). It is particularly important to investigate mechanisms of differential metabolic effects of various statins in patients at risk for metabolic diseases, including diabetes, obesity, and metabolic syndrome.
Please note: This study was partly supported by an established investigator award (2009-1) from Gil Medical Center, Gachon University (Incheon, Korea), and by a grant to Dr. Quon from the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health.
- American College of Cardiology Foundation
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