Abstract
BackgroundOsteoprotegerin (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.MethodsWe 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.ResultsT2DM 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.ConclusionsOPG 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 registrationCurrent Controlled Trials ISRCTN53177482
Highlights
Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease
Within the normal range, systolic and diastolic blood pressure and heart rate were significantly higher in type 2 diabetes mellitus (T2DM) patients relative to controls (Table 1)
Parameters related to left ventricular (LV) volume and diastolic function were, significantly decreased in patients (Table 2)
Summary
Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. 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. Type 2 diabetes mellitus (T2DM) patients are at high risk of developing cardiovascular disease [1]. Circulating OPG levels were reported as independent predictor of cardiovascular mortality in patients with stable coronary artery disease [9]. In asymptomatic T2DM patients OPG levels predicted subclinical atherosclerosis and cardiovascular events [10]. A 17-year prospective observational study in T2DM patients showed a strong predictive value of OPG for all-cause mortality, independent of conventional risk for cardiovascular disease, including renal function [11]
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