Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications

Objective: Osteoprotegerin (OPG) is a newly identified inhibitor of bone resorption. Recent studies indicate that OPG also acts as an important regulatory molecule in the vasculature. Plasma levels of OPG seem to be elevated in subjects with diabetes as well as in non-diabetic subjects with cardiovascular disease. The aim of the present study was to examine the association between plasma OPG levels and microvascular complications and glycemic control in patients with type 2 diabetes. Design and methods: Four groups of 20 subjects in each, individually matched for age and gender, were included in the study: (i) subjects with normal glucose tolerance (NGT); (ii) subjects with impaired glucose tolerance (IGT); (iii) type 2 diabetic patients without retinopathy; and (iv) type 2 diabetic patients with diabetic maculopathy (DMa). Plasma concentration of OPG was measured in duplicate by a sandwich ELISA method. Furthermore, fundus photography, flourescein angiography, and measurements of urinary albumin excretion rate (RIA) were performed. Results: Plasma OPG was significantly higher in diabetic (iii + iv) than in NGT (i) subjects (3.04+/-0.15 vs 2.54+/-0.16 ng/l, P < 0.05). Plasma OPG was significantly higher in the DMa (iv) group than in the NGT (i) group (3.25+/-0.23 vs 2.54+/-0.16 ng/l, P = 0.01). Moreover, plasma OPG was significantly higher (3.61+/-0.36 ng/l) in the group of diabetic subjects with both microalbuminuria and DMa (n = 7) than in the NGT (i) (2.54+/-0.16 ng/l, P < 0.01), IGT (ii) (2.82+/-0.21 ng/l, P < 0.05), and no retinopathy (iii) groups (2.83+/-0.20 ng/l, P < 0.05). Conclusions: We found increased levels of OPG in plasma from diabetic patients with microvascular complications. This finding indicates that OPG may be involved in the development of vascular dysfunction in diabetes.