Troglitazone-induced changes in adiponectin do not affect endothelial function in diabetes.

OBJECTIVE

Adiponectin has been proposed to be related to endothelial function. We have examined the relationship between the increase in adiponectin levels that is associated with troglitazone treatment and endothelium-dependent vasodilation in type 2 diabetic patients.

RESEARCH METHODS AND PROCEDURES

Seventy-two patients participated in this randomized, placebo-controlled, double-blinded study. High-resolution ultrasound images were used to measure the flow-mediated dilation (endothelium-dependent) and nitroglycerin-induced dilation (endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was employed to measure the vascular reactivity in the forearm skin.

RESULTS

Troglitazone treatment resulted in an average 75% increase in the adiponectin levels, but no changes were observed in the endothelium-dependent vasodilation, any other measurement of vascular reactivity, or any other markers of endothelial activation. Also, no changes were observed in the expression of the receptor for advanced glycation end-products in skin biopsies taken from the forearm. Significant correlations were observed during troglitazone treatment between the changes in the adiponectin levels and the changes in fasting plasma glucose (r = -0.29, p < 0.05), hemoglobin A(1c) (r = -0.30, p < 0.05), total cholesterol (r = 0.25, p < 0.05), and low-density lipoprotein-cholesterol (r = 0.34, p < 0.01).

DISCUSSION

The increase in adiponectin levels after troglitazone treatment is not associated with an improvement in the endothelium-dependent vasodilation, indicating that adiponectin is not a major determinant of endothelial function. In addition, receptor for advanced glycation end-products expression in the skin microcirculation is not affected by troglitazone treatment.