Background: Activin A released from epicardial adipose tissue has been linked to contractile dysfunction and insulin resistance in cardiomyocytes. This study investigated the role of activin A in clinical diabetic cardiomyopathy by assessing whether circulating activin A levels associate with cardiometabolic parameters in men with uncomplicated type 2 diabetes (T2D), and the effects of treatment with pioglitazone versus metformin on these associations. Methods: Seventy-eight men with uncomplicated T2D and fourteen healthy men with comparable age were included, in this randomized, double-blind, active comparator intervention study. All T2D men were on glimipiride monotherapy, and randomized to a 24-week intervention with either pioglitazone or metformin. Cardiac dimensions and -function were measured using magnetic resonance imaging, whilst myocardial glucose metabolism (MMRglu) was determined using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography during a hyperinsulinemic-euglycemic clamp. Results:Circulating activin A levels were comparable in T2D men and controls. Activin A levels were independently inversely associated with MMRglu, and positively with left ventricular mass/volume (LVMV)-ratio in T2D men. Intervention with metformin decreased activin A levels, whereas pioglitazone did not alter activin A levels. The changes in plasma activin A levels were not correlated with the changes in MMRglu following either pioglitazone or metformin treatment. A borderline significant correlation (p = 0.051) of changes in plasma activin A levels and changes in LVMV-ratio was observed after pioglitazone treatment. Conclusions: Circulating activin A levels are associated with impaired myocardial glucose metabolism and high LVMV-ratio in patients with uncomplicated T2D, reflecting a potential detrimental role in early human diabetic cardiomyopathy.Trial registration number: Current Controlled Trials SRCTN53177482. © 2013 Chen et al.; licensee BioMed Central Ltd.
Chen, W. J. Y., Greulich, S., van der Meer, R. W., Rijzewijk, L. J., Lamb, H. J., de Roos, A., … Ouwens, D. M. (2013). Activin a is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes. Cardiovascular Diabetology, 12(1). https://doi.org/10.1186/1475-2840-12-150