Changes of osteoprotegerin before and after insulin therapy in type 1 diabetic patients.

ABSTRACT

OBJECTIVE: Osteoprotegerin (OPG) regulates osteoclast and immune functions and appears to represent a protective factor for vascular system. However, the role of OPG in endothelial dysfunction of type 1 diabetic patients has not been evaluated. The purpose of this study was to investigate the relationship between plasma OPG levels and endothelium-dependent arterial dilation in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: This study subjects included 22 newly diagnosed type 1 diabetic patients and 28 healthy subjects. All patients were then given insulin therapy for 6 months. Plasma OPG concentration was measured in duplicate by a sandwich ELISA method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia and after sublingual glyceryltrinitrate (GTN). RESULTS: Plasma OPG level in patients before treatment was 3.09+/-0.70 ng/L, which was significantly higher than that in control (2.07+/-0.75 ng/L) (p<0.001). After 6 months treatment, OPG levels decreased markedly (2.58+/-0.59 ng/L) (p<0.001). The flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.35+/-0.67%, which was significantly lower than that in control (5.17+/-0.83%) (p<0.001), and improved markedly after 6 months treatment (4.27+/-0.63%) (p<0.001). In multivariate analysis, OPG was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and ultra sensitive C-reactive protein (CRP) at baseline (p<0.01). The absolute changes in OPG showed significant correlation with the changes in endothelium-dependent arterial dilation, FBG, HbA1c, and CRP in diabetic patients during the course of treatment (p<0.01). CONCLUSION: This study shows that plasma OPG levels are elevated in newly diagnosed type 1 diabetic patients, and that plasma OPG levels are significantly associated with endothelial function.