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.

difference in heart rate between inspiration and expiration; LF, square root of power of the low frequency oscillation; LF power, power of the low frequency oscillation; Mean RR, mean of all normal RR intervals; Mean RR D-N, difference between awake and sleep time in mean RR; RSA, respiratory sinus arrhythmia; SDANN, standard deviation of the mean RR in all 5 min segments in a 24 h period; SDNN, standard deviation of all normal RR intervals; SDNN index, mean of SD's calculated on 5 min of RR intervals during a 24 h period; SE, standard error; sNN6%, number of successive RR interval differences > 6%, standardized to 24 h; sNN50, number of successive RR interval differences > 50 ms, standardized to 24 h; UAE, urine albumin excretion. AbstractAims/hypothesis. Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In nondiabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that β-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional β-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. Methods. We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, Corresponding author: Dr. E. Ebbehøj, Medical Department M (Diabetes and Endocrinology), Aarhus Kommunehospitalet, DK-8000 Aarhus Denmark, E-mail: e.ebbehoj@dadlnet.dk Abbreviations: AMBP, Ambulatory blood pressure; CCVHF, coefficient of component variance for HF; CCVLF, coefficient of component variance for LF; HF, square root of power of the high frequency oscillation; HF power, power of the high frequency oscillation; HRV, heart rate variability; HRV index, geometric index of total variability in a 24 h period; I-E diff, Diabetologia (2002) 45:965-975 DOI 10.1007 Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. Results. Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in...

Acute hyperglycaemia does not seem to increase plasma levels of OPG in non-diabetic subjects, whereas hyperinsulinaemia may suppress plasma levels of OPG. This finding indicates that the elevated plasma levels of OPG observed in diabetic subjects with poor metabolic control cannot be ascribed to hyperglycaemia per se.