Simvastatin Reduces Insulin Sensitivity in Patients With High Cholesterol
Although simvastatin improves flow-mediated dilation in
hypercholesterolemic patients, the drug reduces adiponectin levels and
insulin sensitivity, according to a report in the April issue of
Diabetes Care. These effects were not dose-dependent and also did not
relate to the magnitude of apolipoprotein B reduction.

In earlier studies, Dr. Kwang Kon Koh and colleagues had shown that
certain drugs, such as fenofibrate and candesartan, increase levels of
adiponectin, a cytokine secreted by fat cells, and enhance insulin
sensitivity. Conversely, in another study, the team found evidence that
simvastatin has exactly the opposite effect.

To explore this further, the researchers assessed adiponectin levels and
insulin sensitivity in 156 hypercholesterolemic patients who were
randomized to receive placebo or simvastatin at one of four doses (10,
20, 40 or 80 mg) during a 2-month period. In addition, flow-mediated
dilation was assessed in all subjects using standard measures.

As anticipated, simvastatin use reduced total cholesterol, LDL
cholesterol, and apolipoprotein B levels, Dr. Koh, from Gachon
University in Incheon, Korea, and colleagues note. In addition, the drug
improved flow-mediated dilation.
By contrast, relative to baseline or placebo, simvastatin reduced
adiponectin levels and insulin sensitivity, independent of the dose or
the drop in apolipoprotein B level.

"Because of reciprocal relationships between endothelial dysfunction and
insulin resistance, we hypothesized that improvements in endothelial
dysfunction may be accompanied by simultaneous improvement in metabolic
parameters," the authors note. This, however, was not the case.

The findings "suggest that not all mechanisms for improving endothelial
dysfunction are tightly coupled to metabolic homeostasis," they add.

Diabetes Care 2008;31:776-782.