Objectives: The bone-related peptide osteoprotegerin (OPG) was recently found in high concentration inside vascular tissues in diabetic patients. OPG is produced by vascular smooth muscle cells and endotheliocytes, and inhibits progression of advanced plaque by delaying size progression as well as plaque calcification. We aimed at determining in type 2 diabetes patients the relationship between serum OPG and circulating level of angiotensin II (AngII), but also the relationship between serum OPG and either lower-limb atherosclerotic peripheral arterial disease (PAD) and/or mediacalcinosis (MC). Research design and methods: Serum OPG was determined in 37 adult patients with type 2 diabetes using an ELISA method. Circulating level of AngII were measured by conventional methods. Patients were divided into three groups: group 1: PAD(−)/MC(−) (n=12); group 2: PAD(+)/MC(−) (n=11); and group 3: PAD(±)/MC(+) (n=14). The groups were matched regarding pharmacotherapy with either angiotensin-converting enzyme inhibitors or sartans. Results: Whereas all type 2 diabetic patients had high levels of OPG (between two- to threefold higher), there were no significant correlations between OPG and the presence of macroangiopathy (either PAD or mediacalcinosis) nor between OPG and aldosteronemia P=0.05), Significant correlations were found between serum OPG and circulating levels of AngII (P=0.03, t ratio −2.13), patients age (P=0.0012), gender (P=0.0084), von Willebrand factor levels (P=0.03) and serum matrix protein Gla level (P=0.02). Conclusion: All type 2 diabetic patients in this study had an increased circulating level of OPG. Serum OPG levels were significantly and positively associated with circulating level of von Willebrand factor. These correlations suggest that OPG is a candidate marker for endothelial dysfunction in type 2 diabetes. The negative correlation between OPG and AngII also point toward a novel potential mechanism for the beneficial pharmaco-therapeutic effect of angiotensin-converting enzyme inhibitors in vascular protection against arterial calcification.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology