Diabetologie und Stoffwechsel 2017; 12(S 01): S1-S84
DOI: 10.1055/s-0037-1601761
Poster: *Poster + Kurzpräsentation
Komplikationen
Georg Thieme Verlag KG Stuttgart · New York

Reduced myocardial mitochondrial oxidative capacity in heart transplant recipients with type 2 diabetes

D Scheiber
1   Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
2   Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
T Jelenik
1   Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
3   German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Partner Düsseldorf, Düsseldorf, Germany
,
P Horn
2   Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
HP Schultheiss
4   Institute for Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany
,
D Lassner
4   Institute for Cardiac Diagnostics and Therapy (IKDT), Berlin, Germany
,
U Boeken
5   Clinic for Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
D Saeed
5   Clinic for Cardiovascular Surgery, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
M Kelm
2   Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
6   Cardiovascular Research Institute Düsseldorf, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
M Roden
1   Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
3   German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Partner Düsseldorf, Düsseldorf, Germany
7   Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
R Westenfeld
2   Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
,
J Szendrödi
1   Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
3   German Center for Diabetes Research (DZD e.V.), München-Neuherberg, Partner Düsseldorf, Düsseldorf, Germany
7   Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
05 May 2017 (online)

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Background:

Myocardial mitochondrial function has been suggested to play a pivotal role in pathogenesis of diabetic cardiomyopathy.

Aims:

To establish gold-standard analysis of mitochondrial respiration in endomyocardial biopsies (EMB) to study the impact of Type 2 Diabetes (T2D) on myocardial energy metabolism in heart transplant (HTX) recipients.

Hypothesis:

1. Myocardial mitochondrial respiration analysis using high-resolution respirometry (HRR) is feasible in EMB. 2. Myocardial energy metabolism is impaired in T2D HTX patients.

Methods:

To assess effects of tissue acquisition, we compared excised myocardial samples with ex vivo biopsies using EMB-bioptomes in apex samples obtained during heart surgery in 9 heart failure patients undergoing left-ventricular assist device (LVAD) implantation. Further, tissue samples were obtained from EMB following HTX in patients with T2D and in glucose-tolerant recipients of similar age, body-mass index (BMI) and cardiac output (HTX-T2D: n = 5; 58 ± 6years; cardiac index expressing the ratio of cardiac output to body surface area [CI]: 2.90 ± 0.11 l/min*m2; BMI: 22.2 ± 1.1 kg/m2; HbA1c: 6.5 ± 0.4%; HTX: n = 13; 51 ± 4years; CI: 2.81 ± 0.14 l/min*m2; BMI: 23.8 ± 0.8 kg/m2; HbA1c: 5.6 ± 0.1%, p < 0.05 vs. HTX-T2D). Maximal mitochondrial respiration on citrate cycle derived substrates and octanoylcarnitine was assessed by HRR.

Results:

Excised myocardial samples and bioptome-harvested EMB had equal respiration rates (r = 0.9988, p < 0.0001) with preserved outer mitochondrial membrane integrity tested by cytochrome-c substitution. In HTX-T2D, maximal oxidative capacity was 29% lower compared to glucose-tolerant participants (122.3 ± 8.6 vs. 170.8 ± 19.6 pmol/s*mg, p < 0.05).

Conclusion:

HRR is feasible in EMB and reveals reduced myocardial oxidative capacity in HTX-T2D patients. Longitudinal assessment of mitochondrial respiration in T2D HTX recipients will provide new insights in the role of T2D-induced alterations of myocardial energy metabolism.