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        Troglitazone Improves Endothelial Function And Fasting Plasma Insulin Concentrations

        A DGReview of :"The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial."
        Metabolism: Clinical and Experimental

        03/04/2003
        By Mark Greener


        Troglitazone improved endothelial function and fasting plasma insulin concentrations in recently diagnosed type 2 diabetics, who did not show clinical macrovascular disease.

        Researchers from Harvard Medical School, Boston, United States, enrolled three groups of patients with type 2 diabetes: 27 recently diagnosed patients without clinical macrovascular disease; 29 patients with long-term diabetes, but without clinical macrovascular manifestations; and 31 patients with diabetes as well as cardiovascular, cerebrovascular, or peripheral vascular disease. Patients took troglitazone, which activates peroxisome proliferator-activator receptor gamma (PPARgamma), or placebo for 12 weeks. The authors assessed the function of endothelial cells, which express PPARgamma.

        Flow-mediated dilation, which is endothelium-dependent, and the fasting insulin level improved in newly diagnosed patients taking troglitazone. Indeed, fasting insulin levels were strongly correlated with changes in flow-mediated dilation. Neither flow-mediated dilation nor fasting insulin levels improved in either of the other groups.

        Troglitazone was not associated with changes in nitroglycerin-induced dilation, which is endothelium-independent, in any group. The authors measured several biochemical markers of endothelial cell activation: von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM) and soluble vascular cell adhesion molecule (sVCAM). Neither these markers nor measurements of microcirculation reactivity changed with troglitazone treatment.

        Patients with long-term diabetes, but without clinical macrovascular manifestations, who received placebo showed a small, but significant, improvement in flow-mediated dilation. The authors suggested that this increase may reflect the low baseline flow-mediated dilation.

        The authors concluded that in patients recently diagnosed with type 2 diabetes and who did not show clinical macrovascular disease, 12 weeks troglitazone treatment enhances endothelial function and this was, in turn, associated with the improved fasting plasma insulin concentrations.
        Metabolism 2003;52:2:173-80. "The effects of troglitazone, an insulin-sensitizing agent, on the endothelial function in early and late type 2 diabetes: a placebo-controlled randomized clinical trial."

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