For patients with coronary artery disease who develop diabetes, pioglitazone improves endothelial dysfunction independently of its beneficial effects on insulin resistance and glycemia, reported Dr. Harald Sourij and his associates at the Medical University of Graz, Austria.
This added benefit is important because “better endothelial function is associated with improved cardiovascular outcome in patients with manifest CAD,” the investigators noted.
Preliminary research indicated glitazones, “a new class of antidiabetic drugs that primarily act via amelioration of insulin resistance,” might also influence endothelial function. The researchers assessed endothelial function in 42 patients with stable CAD and newly diagnosed type 2 diabetes. Their mean age was 60 years.
All participants had profoundly impaired endothelial function when they entered the study. They were randomly assigned to treatment with 30 mg pioglitazone or a placebo once daily for 12 weeks.
Only pioglitazone significantly improved endothelial function. Although the drug also improved insulin resistance and β-cell function, its effects on endothelial function were independent of those metabolic effects (Diabetes Care 2006;29:1039–45).
The drug's mechanism of action is not yet understood. It is known that “oxidative stress and local inflammatory activity play key roles in the pathogenesis of endothelial dysfunction in diabetes,” and the glitazones may reduce the production or availability of nitric oxide as well as decreasing inflammatory factors.
“We suggest our findings justify further research into possible direct effects of glitazones in the vascular wall, as well as into the possible role of endothelial function to predict treatment-induced vascular benefit in glitazone-treated patients,” they said.