title: Long-term severe diabetes only leads to mild cardiac diastolic dysfunction in Zucker diabetic fatty rats.
abstract: OBJECTIVE
  Type 2 diabetes mellitus (DM) leads to cardiac dysfunction irrespective of hypertension and coronary artery disease; this is called diabetic cardiomyopathy. Here, we investigated the severity of diabetic cardiomyopathy and myocardial remodelling in aged Zucker diabetic fatty (ZDF) rats.
  
  
  RESULTS
  Body weight, blood glucose and glycated haemoglobin (Hb(A1c)) levels, and urinary albumin excretion were monitored regularly in ZDF rats (n = 19) and control littermates (n = 19) up to age 45 weeks. ZDF rats were severely diabetic during the entire study period and demonstrated decreased body and heart weights at sacrifice. Left ventricular (LV) function was determined using magnetic resonance imaging (MRI) at age 44 weeks and revealed similar LV ejection fraction and cardiac output index in control and ZDF rats, indicating preserved systolic function. LV pressure characteristics assessed at age 45 weeks showed significant, but mild elevations of LV end-diastolic pressure (+45%) and relaxation time constant Tau (+54%) in ZDF rats, indicating diastolic dysfunction. Histological analyses revealed a significantly increased LV collagen content (+50%), but no cardiomyocyte hypertrophy in ZDF rats.
  
  
  CONCLUSIONS
  The present study clearly shows that long term, severe DM in 45-week-old ZDF rats resulted in relatively mild impairment of diastolic LV function, whereas systolic function was well preserved. These data do not support the notion that diabetes per se is a critical factor in the induction of a clinically relevant degree of cardiac dysfunction. Co-morbidities such as hypertension and coronary artery disease probably have larger impacts on myocardial function in diabetic individuals.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Daniels
authors.forename: Dominik
authors.initials: D
authors.lastname: Linz
authors.forename: Marc
authors.initials: M
authors.lastname: van Bilsen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rütten
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sadowski
authors.forename: Sven
authors.initials: S
authors.lastname: Ruf
authors.forename: Hans-Paul
authors.initials: HP
authors.lastname: Juretschke
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann-Haefelin
authors.forename: Chantal
authors.initials: C
authors.lastname: Munts
authors.forename: Ger J
authors.initials: GJ
authors.lastname: van der Vusse
authors.forename: Frans A
authors.initials: FA
authors.lastname: van Nieuwenhoven
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000209:etiology / Q000503:physiopathology*; D003971:Diastole; D008297:Male; D051381:Rats; D011924:Rats, Zucker; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*; D020257:Ventricular Remodeling