Glucagon Resistance in Patients With MASLD and T2DM

University of Aarhus

Status

Enrolling

Conditions

Metabolic Associated Fatty Liver Disease

Type 2 Diabetes (T2DM)

Treatments

Other: Glugagon

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT07246421

0092321 (Other Grant/Funding Number)

MASLD_GLUCA2025

Details and patient eligibility

About

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:

Is the sensitivity to glucagon with respect to hepatic FA oxidation and suppression of VLDL-TG secretion impaired in humans with T2DM and MASLD?
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

Enrollment

24 estimated patients

Sex

All

Ages

30 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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
Participation in studies involving radioactive isotopes within the past 3 months
Pregnancy
Severely dysregulated type 2 diabetes mellitus (haemoglobin A1c ≥ 100 mmol/mol)
C-peptide < 200 pmol/L
Previous acute myocardial infarction (AMI)
Clinical symptoms of heart failure
Current or previous malignant disease
Known ongoing systemic disease, except for dyslipidaemia and hypertension
Regular use of medication that may affect lipid and glucose metabolism, including insulin treatment, regular use of over-the-counter medications, and hormonal contraception. Exceptions:
1. Participants treated with statins may be included following a 2-week washout period prior to the experimental study day.
2. Participants receiving oral glucose-lowering therapy for T2DM and antihypertensive medication may be included provided that medication is withheld on the study day only.
3. Participants receiving weekly injectable glucagon-like peptide-1 receptor agonists (GLP-1 analogues) may be included following a 1-week washout period prior to the study day.