Clinical trial NCT03386864: Metabolic Determinants of Cardiac Function
Official title: Metabolic Determinants of Cardiac Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Diabetes Mellitus
Keywords: Heart Failure, Diabetes Mellitus, Mitochondrial Respiration
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Heinrich-Heine University, Duesseldorf
First posted: 2017-12-29
Enrollment: 400
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: patients undergoing myocardial biopsy, left ventricular assist device implantation or heart transplantation for medical reasons

Brief summary: Assessment of cardiac energy metabolism in patients with impaired glucose tolerance

Detailed description: Insulin resistance, hepatocellular lipids (HCL) and plasma concentrations of free fatty acids (FFA) are predictors of heart failure, the leading cause of mortality in patients suffering from type 2 diabetes mellitus (T2DM). Epidemiological data suggest that diabetic cardiomyopathy (DC) presents as ventricular dysfunction in patients with T2DM independent of coronary artery disease. The underlying cellular mechanisms are poorly understood. Reduced mitochondrial activity and insulin resistance of skeletal muscle relates to liver steatosis, possibly due to higher substrate flux to the liver. High oxidation rates in the liver result in oxidative stress, damage of mitochondria and apoptosis. The investigators hypothesize that (i) HCL and impaired liver energy metabolism correlate with ventricular dysfunction, (ii) impaired glucose uptake and mitochondrial capacity in skeletal muscle relates to enhanced oxidative capacity, oxidative stress and lipid deposition in heart tissue (iii) reduced myocardial oxidative capacity limits recovery of myocardial function in patients with acute heart failure.

The investigators aim to assess (i) liver energy metabolism and heart function, (ii) respiration and lipid metabolites in skeletal muscle and heart tissue in humans with advanced heart failure and (iii) the prognostic impact of these factors in humans with acute heart failure.

This study will improve the understanding of mechanisms underlying the development of DC and the identification of patients at risk for poor outcome in heart failure.

Eligibility criteria: Inclusion Criteria:

* age ≥ 20 and ≤85 years
* myocardial biopsy for medical reason

Exclusion Criteria:

* acute infection
* autoimmune disease
* pregnancy
* cancer

Primary outcomes:
measure: mitochondrial oxygen flux
timeFrame: Up to 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: German Diabetes Center
state: NRW
Study officials:
affiliation: German Diabetes Center
name: Julia Szendroedi, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zweck E, Scheiber D, Jelenik T, Bonner F, Horn P, Pesta D, Schultheiss HP, Boeken U, Akhyari P, Lichtenberg A, Kelm M, Roden M, Westenfeld R, Szendroedi J. Exposure to Type 2 Diabetes Provokes Mitochondrial Impairment in Apparently Healthy Human Hearts. Diabetes Care. 2021 May;44(5):e82-e84. doi: 10.2337/dc20-2255. No abstract available.
citation: Jelenik T, Flogel U, Alvarez-Hernandez E, Scheiber D, Zweck E, Ding Z, Rothe M, Mastrototaro L, Kohlhaas V, Kotzka J, Knebel B, Muller-Wieland D, Moellendorf S, Godecke A, Kelm M, Westenfeld R, Roden M, Szendroedi J. Insulin Resistance and Vulnerability to Cardiac Ischemia. Diabetes. 2018 Dec;67(12):2695-2702. doi: 10.2337/db18-0449. Epub 2018 Sep 26.