Glucagon Resistance in Patients With MASLD and T2DM
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age30-70
SponsorUniversity of Aarhus
About this trial
The goal of this clinical trial is to investigate the sensitivity to glucagon in patients with type 2 diabetes mellitus (T2DM), with and without metabolic associated fatty liver disease (MASLD).
The main questions it aims to answer are:
1. Is the sensitivity to glucagon with respect to hepatic FA oxidation and suppression of VLDL-TG secretion impaired in humans with T2DM and MASLD? 2. Is glucagon resistance and MASLD reflected in an aberrated lipidomic/metabolomic profile in blood and adipose tissue?
Researchers will compare patients with T2DM with and without MASLD to see if the response to basal and high levels of glucagon differs between the groups.
Participants will attend 2 short visits and 1 full-day visit, including:
* Body scan (DXA) to check fat and bone composition * MRI to measure liver fat. * Blood tests. * Ultrasound to check liver stiffness and scarring. * Fat biopsies * 8-hour hormone (including glucagon) and tracer infusion * PET-CT scans
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
BMI > 26 kg/m²
confirmed diagnosis of Type 2 Diabetes Mellitus (T2DM) min. 6 months prior enrollment
steatosis FF% > 5,6% on MR spectroscopy for MAFLD group
Disqualifiers
Alcohol abuse (>10 units per week for both sexes) or other substance abuse
Smoking
Current or previous malignant disease
Blood donation within the last 3 months prior to the study day
Trial design
Design model
Parallel
Treatments tested in this trial
Glugagon
Other interventionInfusion of low dose glucagon and high dose glucagon during simultaneous somatostatin infusion and replacement doses of insulin and growth hormone. Infusion of palmitate, VLDL-triglyceride and glucose tracers. \[11C\]palmitate PET during low and high dose glucagon.
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: Subjects with T2DM and MR spectroscopy verified NO steatosisActive comparator 1 intervention
Group B: Subjects with T2DM and MR spectroscopy verified steatosisActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Hepatic FFA oxidation rate (µmol/100Ml/min)
Measured using \[11C\]palmitate positron-emission tomography (PET)
Time frame
30 minutes at steady-state2
Blood and adipose tissue proteomic and lipidomic profiles
Mass spectrometry-based lipidomic/proteomic profiles of paired adipose and plasma samples.
Time frame
30 minutes after steady-stateSecondary outcomes
1
Endogen glucose production (mmol/kg/min)
3-3H glucose tracer technique
Time frame
30 minutes at steady-state2
Fatty acid turnover (µmol/min)
Infusion af \[9,10-3H\] palmitate and measurement of specific activity
Time frame
30 minutesat steady-state3
VLDL-triglyceride kinetics (appearance rate (µmol/min) and oxidation (µmol/min))
Ex vivo labeled VLDL \[14C\]-triolein tracer technique. Oxidation is measured by specific activity in exhaled air.
Time frame
30 minutes at steady-stateSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Aarhus
Lead sponsor
Novo Nordisk A/S
Collaborator
Source ClinicalTrials.gov