Statin treatment may improve cardiovascular risk profiles for some patients through a decrease in risk for type 2 diabetes, according to a presentation at the American Physiology Society-sponsored conference, Experimental Biology 2003.

Over the past decade, evidence has accumulated indicating that nitric oxide may play a key role in control of metabolic and cardiovascular homeostasis: Mice that do not have the gene for endothelial nitric oxide synthase are both insulin resistant and hypertensive.

The current study shows that stimulating nitric oxide bioavailability with use of statins may represent a new way to improve metabolic control.

A Swiss research team identified two groups of mice. The first group showed partial deficiency in enzyme activity; they were heterozygous for a functional allele. The second group of mice had no enzyme activity; they were homozygous for the nonfunctional allele.

Half of the first group was treated with simvastatin, while the other was fed an inert vehicle (no treatment). Half of the simvastatin group was fed a high-fat diet for 8 weeks, whereas the other half received a normal diet. The same dietary steps were taken for the no treatment mice.

Arterial pressure and insulin sensitivity were measured at the end of the 8-week period.
A high-fat diet caused both arterial hypertension and insulin resistance in the heterozygous mice that received inert vehicle. In contrast, the mice in the simvastatin group that were fed a high-fat diet did not show either insulin resistance or arterial hypertension. In the homozygous mice (those without enzyme activity), all of the mice showed similar levels of insulin resistance and arterial hypertension.

These findings provide the first evidence that simvastatin can prevent diet-induced arterial hypertension and insulin resistance in mice with some level of endothelial nitric oxide synthase activity. The data suggest that simvastatin may improve cardiovascular risk in some human patients through nitric oxide?mediated improvements in insulin sensitivity and arterial pressure.