Hepatic and Cardiac Metabolic Flexibility in Subjects With T2DM With and Without NAFLD

University of Aarhus

Status

Completed

Conditions

NAFLD - Non-Alcoholic Fatty Liver Disease

Type 2 Diabetes

Treatments

Other: Hyperinsulinemic euglycaemic clamp

Study type

Interventional

Funder types

Other

Identifiers

NCT04698486

74772

Details and patient eligibility

About

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.

Enrollment

17 patients

Sex

All

Ages

30 to 70 years old

Volunteers

Accepts Healthy Volunteers

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