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

Investigation of Hepatic and Cardiac Fatty Acid Metabolism in Patients With Type 2 Diabetes Mellitus With and Without Non-alcoholic Fatty Liver Disease


Lead Sponsor: University of Aarhus

Collaborator: Danish Diabetes Academy

Source University of Aarhus
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.

Overall Status Recruiting
Start Date July 3, 2020
Completion Date January 1, 2022
Primary Completion Date January 1, 2022
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Fatty acid uptake in Heart (mg/kg/min) 1 day
Fatty acid oxidation in Heart (µmol/min) 1 day
Secondary Outcome
Measure Time Frame
VLDL-triglyceride secretion (µmol/min) 1 day
VLDL-triglyceride oxidation (µmol/min) 1 day
Fatty acid uptake in liver (mg/kg/min) 1 day
Fatty acid oxidation in liver (µmol/min) 1 day
VLDL-triglyceride uptake in muscle (percent) 1 day
VLDL-triglyceride uptake in adipose tissue (percent) 1 day
Enrollment 20

Intervention Type: Other

Intervention Name: Hyperinsulinemic euglycaemic clamp

Description: Infusion of constant intravenous insulin to achieve hyperinsulinemia and concomitant infusion of glucose to maintain euglycemia (plasma glucose at 5 mM). Infusion of palmitate and VLDL-triglyceride tracer. PET/CT scans of heart and liver, both in basal period and during intervention.



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

Gender: All

Minimum Age: 30 Years

Maximum Age: 70 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Contact

Last Name: Indumathi Kumarathas, MD

Phone: +4530299715

Email: [email protected]

Facility: Status: Department of Diabetes and Hormone diseases in Aarhus University Hospital
Location Countries


Verification Date

December 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Type 2 Diabetes with NAFLD

Type: Active Comparator

Description: Patients with Type 2 Diabetes with NAFLD MR spectroscopy verified no steatosis

Label: Type 2 Diabetes without NAFLD

Type: Active Comparator

Description: Patients with Type 2 Diabetes without NAFLD MR spectroscopy verified steatosis

Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov