title: Activin A is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes.
abstract: 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.
  
  
  BACKGROUND
  Current Controlled Trials SRCTN53177482.
authors.forename: Weena J Y
authors.initials: WJ
authors.lastname: Chen
authors.forename: Sabrina
authors.initials: S
authors.lastname: Greulich
authors.forename: Rutger W
authors.initials: RW
authors.lastname: van der Meer
authors.forename: Luuk J
authors.initials: LJ
authors.lastname: Rijzewijk
authors.forename: Hildo J
authors.initials: HJ
authors.lastname: Lamb
authors.forename: Albert
authors.initials: A
authors.lastname: de Roos
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Ruige
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany. margriet.ouwens@ddz.uni-duesseldorf.de.
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
mesh_terms: D028341:Activins / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D058065:Diabetic Cardiomyopathies / Q000378:metabolism; D004311:Double-Blind Method; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D028322:Inhibin-beta Subunits / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009929:Organ Size; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D007004:Hypoglycemic Agents; D019275:Radiopharmaceuticals; D045162:Thiazolidinediones; C422405:activin A; C103008:inhibin beta A subunit; D019788:Fluorodeoxyglucose F18; D028341:Activins; D008687:Metformin; D028322:Inhibin-beta Subunits; D005947:Glucose; D000077205:Pioglitazone