Clinical Research
Lipid Disorders
Atorvastatin Causes Insulin Resistance and Increases Ambient Glycemia in Hypercholesterolemic Patients

Presented at the European Society of Cardiology 2009, Barcelona, Spain, August 29 to September 2, 2009, and American Heart Association Scientific Sessions 2009, Orlando, Florida, November 14 to 18, 2009.
https://doi.org/10.1016/j.jacc.2009.10.053Get rights and content
Under an Elsevier user license
open archive

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)

Key Words

adipocytokines
glycated hemoglobin
insulin resistance
metabolic syndrome
statins

Abbreviations andAcronyms

ANOVA
analysis of variance
CI
confidence interval
HbA1C
glycated hemoglobin A1C
hsCRP
high-sensitivity C-reactive protein
LDL
low-density lipoprotein
QUICKI
Quantitative Insulin-Sensitivity Check Index

Cited by (0)

This study was supported by grants from established investigator award (2005-1, 2006-1) (Dr. Koh), Gachon University Gil Hospital, and the Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health (NIH) (Dr. Quon).