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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.