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Atorvastatin Causes Insulin Resistance and Increases Ambient Glycemia in Hypercholesterolemic Patients
Open accessAbstract
Objectives We investigated whether atorvastatin might decrease insulin sensitivity and increase ambient glycemia in hypercholesterolemic patients.Background Clinical trials suggest that some statin treatments might increase the incidence of diabetes despite reductions in low-density lipoprotein (LDL) cholesterol and improvement in endothelial dysfunction.Methods A randomized, single-blind, placebo-controlled parallel study was conducted in 44 patients taking placebo and in 42, 44, 43, and 40 patients given daily atorvastatin 10, 20, 40, and 80 mg, respectively, during a 2-month treatment period.Results Atorvastatin 10, 20, 40, and 80 mg significantly reduced LDL cholesterol (39%, 47%, 52%, and 56%, respectively) and apolipoprotein B levels (33%, 37%, 42%, and 46%, respectively) after 2 months of therapy when compared with either baseline (all p < 0.001 by paired t test) or placebo (p < 0.001 by analysis of variance [ANOVA]). Atorvastatin 10, 20, 40, and 80 mg significantly increased fasting plasma insulin (mean changes: 25%, 42%, 31%, and 45%, respectively) and glycated hemoglobin levels (2%, 5%, 5%, and 5%, respectively) when compared with either baseline (all p < 0.05 by paired t test) or placebo (p = 0.009 for insulin and p = 0.008 for glycated hemoglobin by ANOVA). Atorvastatin 10, 20, 40, and 80 mg decreased insulin sensitivity (1%, 3%, 3%, and 4%, respectively) when compared with either baseline (p = 0.312, p = 0.008, p < 0.001, and p = 0.008, respectively, by paired t test) or placebo (p = 0.033 by ANOVA).Conclusions Despite beneficial reductions in LDL cholesterol and apolipoprotein B, atorvastatin treatment resulted in significant increases in fasting insulin and glycated hemoglobin levels consistent with insulin resistance and increased ambient glycemia in hypercholesterolemic patients. (Effects of Atorvastatin on Adiponectin Levels and Insulin Sensitivity In Hypercholesterolemic Patients; NCT00745836).
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“The 3 studies by Koh et al. (19,20,22) from 2008, 2009, and 2010 used the Quantitative Insulin-Sensitivity Check Index as a surrogate measure for insulin sensitivity, whereas the study by Ohrvall et al. (21) from 1995 used the hyperinsulinemic-euglycemic clamp technique.”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [22]
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“Recently, it has been reported that statin treatment impairs insulin sensitivity and increases the prevalence of type 2 diabetes (19 -22); and it seems that lipophilic statins (i.e., simvastatin, atorvastatin, fluvastatin, lovastatin) have a more pronounced effect on insulin sensitivity compared with hydrophilic statins (i.e., pravastatin, rosuvastatin) (23).”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [22]
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Metadata
- Authors
- Koh, K. K., Quon, M. J., Han, S. H., Lee, Y., Kim, S. J., & Shin, E. K.
- Affiliations
- Gachon University Gil Medical Center (KR)
- National Institutes of Health (US)
- University of Seoul (KR)
- Corresponding author
- Koh, Kwang Kon
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 55
- Issue
- 12
- Pages
- 1209-1216
- ISSN
- 0735-1097 (ISSN-L)
- PMC
- PMC3016087
- OpenAlex
- W2052703897
- Cited by
- 229
- References
- 27
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 9 · 2023: 16 · 2022: 9 · 2021: 8 · 2020: 5 · 2019: 13 · 2018: 9 · 2017: 11 · 2016: 13 · 2015: 18 · 2014: 31 · 2013: 23 · 2012: 23
- FWCI
- 24.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- established investigator award
- Gachon University Gil Hospital
- Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- atorvastatin, insulin resistance, hypercholesterolemia, statins, fasting insulin, HbA1c, LDL cholesterol, apolipoprotein B, diabetes risk, dose-dependent effects, endothelial dysfunction, endothelial nitric oxide synthase, nitric oxide, nitric oxide synthase inhibition, hypertriglyceridemia
- MeSH terms
- Atorvastatin, Adult, Aged, Blood Glucose, Double-Blind Method, Female, Heptanoic Acids, Humans, Hypercholesterolemia, Insulin, Insulin Resistance, Male, Middle Aged, Pyrroles, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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