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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
24
Infusion 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.
Aarhus University Hospital
Aarhus, Denmark
RECRUITINGHepatic FFA oxidation rate (µmol/100Ml/min)
Measured using \[11C\]palmitate positron-emission tomography (PET)
Time frame: 30 minutes at steady-state
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-state
Endogen glucose production (mmol/kg/min)
3-3H glucose tracer technique
Time frame: 30 minutes at steady-state
Fatty acid turnover (µmol/min)
Infusion af \[9,10-3H\] palmitate and measurement of specific activity
Time frame: 30 minutesat steady-state
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-state
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