Effects of exenatide on cardiac function, perfusion, and energetics in type 2 diabetic patients with cardiomyopathy: a randomized controlled trial against insulin glargine

Weena J Y Chen, Michaela Diamant, Karin de Boer, Hendrik J Harms, Lourens F H J Robbers, Albert C van Rossum, Mark H H Kramer, Adriaan A Lammertsma, Paul Knaapen, Weena J Y Chen, Michaela Diamant, Karin de Boer, Hendrik J Harms, Lourens F H J Robbers, Albert C van Rossum, Mark H H Kramer, Adriaan A Lammertsma, Paul Knaapen

Abstract

Background: Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.

Methods and results: Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed. Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [15O]H2O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls. Myocardial oxygen consumption and myocardial efficiency, measured using [11C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.

Conclusions: T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism. Trial registration NCT00766857.

Keywords: Cardiac function; Diabetes mellitus type 2; Exenatide; Myocardial oxidative metabolism; Myocardial perfusion.

Figures

Fig. 1
Fig. 1
Flowchart of type 2 diabetic patient disposition. LV left ventricular
Fig. 2
Fig. 2
Resting, and hyperemic myocardial blood flow, and coronary flow reserve (CFR) in healthy controls (triangles) and type 2 diabetic (T2DM) patients (lozenges). *P = 0.02, †P < 0.01
Fig. 3
Fig. 3
Association between left ventricular (LV) ejection fraction and myocardial efficiency in healthy controls (white triangles) and type 2 diabetic (T2DM) patients (black lozenges)
Fig. 4
Fig. 4
Left ventricular (LV) ejection fraction in type 2 diabetic patients at baseline and after 26-weeks of exenatide [dots; open dots (mean ± SD)] versus insulin glargine [squares; open squares (mean ± SD)]
Fig. 5
Fig. 5
a Hyperemic myocardial blood flow (MBF) and b coronary flow reserve in type 2 diabetic patients at baseline and after 26-weeks of exenatide [dots; open dots (mean ± SD)] versus insulin glargine [squares; open squares (mean ± SD)]
Fig. 6
Fig. 6
Myocardial efficiency in type 2 diabetic patients at baseline and after 26-weeks of exenatide [dots; open dots (mean ± SD)] versus insulin glargine [squares; open squares (mean ± SD)]

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