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

Abstract

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 þ 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 ¼ 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 ¼ 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.

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

“…This was first shown by Browner et al [12], who reported that although no associations were seen between the bone parameters and plasma osteoprotegerin levels, individuals with diabetes as well as persons with cardiovascular disease had increased values. Since then, these findings have been confirmed in both type 1 [38,39] and type 2 diabetes [13,40]. Moreover, we recently found that plasma osteoprotegerin is increased in subgroups of type 1 diabetic patients with nephropathy and in subgroups with signs of cardiovascular disease [18].…”

“…Cardiovascular disease was considered present at baseline in patients with a history of admission for stroke or myocardial infarction. Plasma osteoprotegerin was measured by a sandwich ELISA using commercially available antibodies (R&D Systems, Minneapolis, MN, USA), as previously described [13]. Briefly, mouse antihuman osteoprotegerin (R&D Systems) was used as capture antibody and a biotinylated goat anti-human osteoprotegerin (R&D Systems) for detection.…”

“…Plasma levels are increased in patients with diabetes [12,13] as well as in non-diabetic individuals with coronary artery disease [12,14,15]. Of particular interest, the plasma osteoprotegerin concentration correlates to the degree of arterial calcification [16,17], a phenomenon often observed in patients with diabetes [16,17].…”

“…Of particular interest, the plasma osteoprotegerin concentration correlates to the degree of arterial calcification [16,17], a phenomenon often observed in patients with diabetes [16,17]. Furthermore, a relationship between increased plasma osteoprotegerin concentration and micro-and macrovascular parameters has been observed in patients with type 1 [18] and type 2 diabetes [13]. In addition, a few recent studies indicate that plasma osteoprotegerin may be a strong and independent predictor of cardiovascular events in some populations.…”

Vascular calcification and osteolysis in diabetic neuropathy?is RANK-L the missing link?

“…Browner and colleagues found that serum OPG concentrations were higher in women with diabetes and that they correlated with cardiovascular risk [28]. Serum concentrations of OPG were also found to be higher in another small study of patients with Type 2 diabetes, and possibly associated specifically with microvascular complications [29]. There is evidence that the OPG/RANK-L system is involved in the accelerated vascular calcification of chronic renal failure [30], and it has been shown that it is modulated in vitro by inorganic phosphate [31].…”