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Diabetes Care. 2009 Feb;32(2):209-14. doi: 10.2337/dc08-1123. Epub 2008 Oct 28.

Effects of high-dose simvastatin therapy on glucose metabolism and ectopic lipid deposition in nonobese type 2 diabetic patients.

Author information

1
Department of Internal Medicine 3, Medical University of Vienna, Vienna, Austria.

Abstract

OBJECTIVE:

Statins may exert pleiotropic effects on insulin action that are still controversial. We assessed effects of high-dose simvastatin therapy on peripheral and hepatic insulin sensitivity, as well as on ectopic lipid deposition in patients with hypercholesterolemia and type 2 diabetes.

RESEARCH DESIGN AND METHODS:

We performed a randomized, double-blind, placebo-controlled, single-center study. Twenty patients with type 2 diabetes received 80 mg simvastatin (BMI 29 +/- 4 kg/m2, age 55 +/- 6 years) or placebo (BMI 27 +/- 4 kg/m2, age 58 +/- 8 years) daily for 8 weeks and were compared with 10 healthy humans (control subjects; BMI 27 +/- 4 kg/m2, age 55 +/- 7 years). Euglycemic-hyperinsulinemic clamp tests combined with D-[6,6-d2]glucose infusion were used to assess insulin sensitivity (M) and endogenous glucose production (EGP). 1H magnetic resonance spectroscopy was used to quantify intramyocellular and hepatocellular lipids.

RESULTS:

High-dose simvastatin treatment lowered plasma total and LDL cholesterol levels by approximately 33 and approximately 48% (P < 0.005) but did not affect M, intracellular lipid deposition in soleus and tibialis anterior muscles and liver, or basal and insulin-suppressed EGP. In simvastatin-treated patients, changes in LDL cholesterol related negatively to changes in M (r = -0.796, P < 0.01). Changes in fasting free fatty acids (FFAs) related negatively to changes in M (r = -0.840, P < 0.01) and positively to plasma retinol-binding protein-4 (r = 0.782, P = 0.008).

CONCLUSIONS:

High-dose simvastatin treatment has no direct effects on whole-body or tissue-specific insulin action and ectopic lipid deposition. A reduction in plasma FFAs probably mediates alterations in insulin sensitivity in vivo.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00704314.

PMID:
18957532
PMCID:
PMC2628681
DOI:
10.2337/dc08-1123
[Indexed for MEDLINE]
Free PMC Article

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