Editors' ChoiceDiabetes

Hard on the Heart

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Science Translational Medicine  31 Aug 2011:
Vol. 3, Issue 98, pp. 98ec138
DOI: 10.1126/scitranslmed.3003105

Diabetes mellitus (DM) can make a person heartsick. And with nearly 350 million people living with DM worldwide, the resulting economic and quality-of-life costs can give one palpitations. Commonly, physicians focus on the clogging effects DM has on the coronary vasculature and the associated increased risk of heart attack. More recently, however, DM has been found to contribute to the stiffness and distensibility of the heart tissue, which causes exercise intolerance and eventually heart failure. To assess the effects of DM on cardiac muscle at the cellular level, Falcão-Pires et al. studied patients who have aortic stenosis (AS), either with or without DM, and controls that suffer from neither disorder.

AS is a narrowing of the aortic valve that causes an outflow-tract obstruction and results in thickening and stiffening of the left ventricular muscle of the heart. Surgical valve replacement is often the treatment of choice for AS. The researchers used echocardiography to measure heart hemodynamics in AS patients with and without DM who underwent aortic valve replacement. The authors also acquired myocardial tissue from the left ventricles of these AS patients and of controls, which included explanted donor hearts and patients with arrhythmia who underwent cardiac biopsy. Microscopic evaluation of heart tissue organization and structure (histomorphometry) as well as immunochemistry techniques revealed a larger myocardial collagen fraction (which indicates increased fibrosis) in samples from patients with AS and DM versus patients with AS alone or control subjects. This increase in fibrosis correlated with higher left-ventricular end-diastolic pressure (which indicates reduced relaxation of the left ventricle) measured in the echocardiograms. Vascular tissue from patients with DM and AS contained more deposition of advanced glycation end products relative to patients with AS alone, and this increase was associated with worse diastolic dysfunction. Cardiomyocyte dimension and resting tension were both higher in patients with DM and AS versus patients with AS alone or control subjects. These findings highlight the additive adverse effects that DM has on myocardial cells in the context of valve disease and imply that DM prevention parameters might spawn an increase in the number of healthy hearts.

I. Falcão-Pires et al., Diabetes mellitus worsens diastolic left ventricular dysfunction in aortic stenosis through altered myocardial structure and cardiomyocyte stiffness. Circulation 15 August 2011 (10.1161/ CIRCULATIONAHA.111.025270). [Abstract]

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