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Open Access Original investigation

Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men

Weena JY Chen1*, Luuk J Rijzewijk1, Rutger W van der Meer2, Martijn W Heymans3, Eelco van Duinkerken1, Mark Lubberink4, Adriaan A Lammertsma4, Hildo J Lamb2, Albert de Roos2, Johannes A Romijn5, Jan WA Smit5, Jeroen J Bax6, Mette Bjerre7, Jan Frystyk7, Allan Flyvbjerg7 and Michaela Diamant1

Author Affiliations

1 Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands

2 Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands

3 Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands

4 Department of Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands

5 Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, the Netherlands

6 Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands

7 Medical Department of Endocrinology and Internal Medicine, Aarhus University Hospital & The Medical Research Laboratories, Clinical Institute, Aarhus University, Aarhus, Denmark

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Cardiovascular Diabetology 2011, 10:67  doi:10.1186/1475-2840-10-67

Published: 19 July 2011



Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. Negative associations exist between circulating OPG and cardiac function. The adipocytokine adiponectin (ADPN) is downregulated in type 2 diabetes mellitus (T2DM) and coronary artery disease and shows an inverse correlation with insulin sensitivity and cardiovascular disease risk. We assessed the relationship of plasma OPG and ADPN and arterial function, cardiac function and myocardial glucose metabolism in T2DM.


We included 78 asymptomatic men with uncomplicated, well-controlled T2DM, without inducible ischemia, assessed by dobutamine-stress echocardiography, and 14 age-matched controls. Cardiac function was measured by magnetic resonance imaging, myocardial glucose metabolism (MMRglu) by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography. OPG and ADPN levels were measured in plasma.


T2DM patients vs. controls showed lower aortic distensibility, left ventricular (LV) volumes, impaired LV diastolic function and MMRglu (all P < 0.05). In T2DM men vs. controls, OPG levels were higher (P = 0.02), whereas ADPN concentrations were decreased (P = 0.04). OPG correlated inversely with aortic distensibility, LV volumes and E/A ratio (diastolic function), and positively with LV mass/volume ratio (all P < 0.05). Regression analyses showed the associations with aortic distensibility and LV mass/volume ratio to be independent of age-, blood pressure- and glycated hemoglobin (HbA1c). However, the associations with LV volumes and E/A ratio were dependent of these parameters. ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.


OPG was inversely associated with aortic distensibility, LV volumes and LV diastolic function, while ADPN was positively associated with MMRglu. These findings indicate that in asymptomatic men with uncomplicated T2DM, OPG and ADPN may be markers of underlying mechanisms linking the diabetic state to cardiac abnormalities.

Trial registration

Current Controlled Trials ISRCTN53177482

osteoprotegerin; adiponectin; type 2 diabetes mellitus; arterial function; cardiac function; myocardial metabolism