Clinical trial NCT04698486: Hepatic and Cardiac Metabolic Flexibility in Subjects With T2DM With and Without NAFLD
Official title: Investigation of Hepatic and Cardiac Fatty Acid Metabolism in Patients With Type 2 Diabetes Mellitus With and Without Non-alcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NAFLD - Non-Alcoholic Fatty Liver Disease
Type 2 Diabetes
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Danish Diabetes Academy
First posted: 2021-01-07
Enrollment: 17
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH) and cirrhosis. Accumulating evidence indicates that NAFLD is associated with development of heart failure, abnormal ventricular glucose and fatty acid (FA) utilisation and cardiac steatosis. The mechanisms behind why some subjects progress from NAFLD to NASH and the link between cardiac involvement and NAFLD are poorly understood, but must include altered cardiac and intrahepatic lipid handling. Investigators plan comprehensive kinetic studies of heart and liver FA uptake and oxidation, ventricular function and substrate utilisation, and hepatic triglyceride (TG) secretion in order to assess mechanisms governing cardiac and hepatic lipid and glucose trafficking in subjects with type 2 diabetes with and without NAFLD and NASH and the relationship with heart function. In addition, the investigators will assess skeletal muscle and adipose tissue enzyme activities, gene expression and protein concentrations in type 2 diabetic subjects to define mechanisms involved in the cross-talk between heart, liver, muscle and adipose tissues. Investigators will address these questions using tracer techniques (11Cpalmitate PET tracers and triglyceride (TG) tracers) to study cardiac and liver substrate trafficking, as well as MR spectroscopy, echocardiography, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression. The overarching goals are to define abnormalities and differences between NAFLD and NASH in hepatic lipid (FA and TG) metabolism.


Eligibility criteria: Inclusion Criteria:

* Subjects with Type 2 Diabetes with and without NAFLD (steatosis FF% \> 5,6% on MR spectroscopy for NAFLD and NASH groups)

Exclusion Criteria:

* Active smoking
* Comorbidity other than hypertension and hyperlipidemia
* Fixed medical drug consumption (including insulin) except statins and anti-diabetic medications. However, statins and weekly based GLP-1 agonist must be paused 1 week before the examination date and other antidiabetic medication 3 days before the study date.
* Patients with cancer or former cancer patients
* Blood donation within the last 3 months prior to the study
* Participation in experiments involving radioactive isotopes within the last 3 months
* Alcohol abuse (over 21 items per week for men and over 14 for women)
* Pregnancy

Primary outcomes:
measure: Fatty acid uptake in Heart (mg/kg/min)
timeFrame: 1 day
measure: Fatty acid oxidation in Heart (µmol/min)
timeFrame: 1 day
Secondary outcomes:
measure: VLDL-triglyceride secretion (µmol/min)
timeFrame: 1 day
measure: VLDL-triglyceride oxidation (µmol/min)
timeFrame: 1 day
measure: Fatty acid uptake in liver (mg/kg/min)
timeFrame: 1 day
measure: Fatty acid oxidation in liver (µmol/min)
timeFrame: 1 day
measure: VLDL-triglyceride uptake in muscle (percent)
timeFrame: 1 day
measure: VLDL-triglyceride uptake in adipose tissue (percent)
timeFrame: 1 day
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Department of Endocrinology and Internal Medicine
Study officials:
References: