Metabolic Determinants of Cardiac Function

NCT ID: NCT03386864

Last Updated: 2023-08-08

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2020-04-30

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.

Conditions

Heart Failure; Diabetes Mellitus

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Control

Control

No interventions assigned to this group

Insulin Resistant

Insulin Resistant

No interventions assigned to this group

Type 2 Diabetes

Type 2 Diabetes

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• acute infection
• autoimmune disease
• pregnancy
• cancer

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: collaborator

German Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julia Szendroedi, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

German Diabetes Center

Locations

German Diabetes Center

Düsseldorf, North Rhine-Westphalia, Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 33972315 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30257974 (View on PubMed)

Other Identifiers

5263R

Identifier Type: -

Identifier Source: org_study_id