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Activin a is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes

Weena JY Chen1, Sabrina Greulich28, Rutger W van der Meer3, Luuk J Rijzewijk1, Hildo J Lamb3, Albert de Roos3, Johannes WA Smit4, Johannes A Romijn5, Johannes B Ruige6, Adriaan A Lammertsma7, Mark Lubberink79, Michaela Diamant1 and D Margriet Ouwens268*

Author Affiliations

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

2 Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany

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

4 Department of General Internal Medicine 463, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands

5 Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands

6 Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

7 Department of Radiology & Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, The Netherlands

8 German Center for Diabetes Research (DZD), Neuherberg, Germany

9 Present address: Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET, Uppsala University, Uppsala, Sweden

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Cardiovascular Diabetology 2013, 12:150  doi:10.1186/1475-2840-12-150

Published: 17 October 2013



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.


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.


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.


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

Activin A; Myocardial glucose metabolism; Cardiac remodeling; Diabetic cardiomyopathy