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

NCT ID: NCT04698486

Last Updated: 2022-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-03
• Study Completion Date: 2021-12-01

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.

Conditions

NAFLD - Non-Alcoholic Fatty Liver Disease; Type 2 Diabetes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Type 2 Diabetes with NAFLD

Patients with Type 2 Diabetes with NAFLD

MR spectroscopy verified no steatosis

Group Type: ACTIVE_COMPARATOR

Hyperinsulinemic euglycaemic clamp

Intervention Type: OTHER

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.

Type 2 Diabetes without NAFLD

Patients with Type 2 Diabetes without NAFLD

MR spectroscopy verified steatosis

Group Type: ACTIVE_COMPARATOR

Hyperinsulinemic euglycaemic clamp

Intervention Type: OTHER

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.

Interventions

Hyperinsulinemic euglycaemic clamp

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Danish Diabetes Academy

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Endocrinology and Internal Medicine

Aarhus N, , Denmark

Countries

Denmark

Other Identifiers

74772

Identifier Type: -

Identifier Source: org_study_id