Glucagon Resistance in Patients With NAFLD

University of Aarhus

Status: Completed

Conditions: Glucose Metabolism Disorders; Non-alcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease

Treatments: Other: glucagon

Study type: Interventional

Funder types: Other

Identifiers

NCT04042142

230279

Details and patient eligibility

About

The investigators propose that the sensitivity to glucagon in hepatic lipid metabolism is impaired in subjects with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH). Moreover, they propose a dys-coordinated, reduced glucagon sensitivity in hepatic lipid metabolism and endogen glucose production in patients with NAFLD and NASH compared with healthy subjects and patients with simple steatosis. This reduced sensitivity may be the basis of a more severe dyslipidemia and the production of increased concentrations of toxic lipid intermediates in plasma and muscle tissue. The study will include healthy subjects with obesity and subjects with simple steatosis and NASH, tested at basal glucagonemia and moderate hyperglucagonemia to mimic insulin resistant levels during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers in combination with indirect calorimetry as well as skeletal and adipose tissue biopsies will be employed to assess free fatty acid and VLDL-triglyceride kinetics (turnover, and oxidation) and hepatic fatty acid-esterification.

Enrollment: 28 patients

Sex: All

Ages: 38 to 68 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• BMI > 28 kg/m2
• steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups

Exclusion criteria

• active smoking
• pregnancy
• comorbidity other than hypertension and hyperlipidemia
• participation in other radioactive isotope studies within the past 3-5 months (depending on radiation dose)
• blood donation (within 3 months)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 3 patient groups

Healthy overweight subjects

Active Comparator group

Description:

MR spectroscopy verified no steatosis

Treatment:

Other: glucagon

Subjects with non-alcoholic fatty liver disease

Active Comparator group

Description:

MR spectroscopy verified steatosis, no steatohepatitis on liver biopsy

Treatment:

Other: glucagon

Subjects with non-alcoholic steatohepatitis

Active Comparator group

Description:

MR spectroscopy verified steatosis, steatohepatitis on liver biopsy

Treatment:

Other: glucagon