Glucagon resistance in MASLD and type 2 diabetes
Mechanisms for Glucagon Resistance as Driver of Metabolic Associated Steatotic Liver Disease and Cardiovascular Disease in Humans With Type 2 Diabetes
This will see if people with type 2 diabetes, with or without MASLD, respond differently to glucagon in liver fat oxidation and VLDL-triglyceride secretion.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 30 Years to 70 Years |
| Sex | All |
| Sponsor | University of Aarhus Academic / other |
| Locations | 1 site (Aarhus) |
| Trial ID | NCT07246421 on ClinicalTrials.gov |
What this trial studies
Researchers will compare adults with type 2 diabetes who have MASLD to those without MASLD to determine whether glucagon's effects on hepatic fatty acid oxidation and suppression of VLDL-TG secretion differ between groups. Participants attend two short visits and one full-day visit for DXA body composition, MRI liver fat measurement, ultrasound elastography, blood tests, adipose tissue biopsies, and PET-CT imaging. During the full-day visit an 8-hour hormone and tracer infusion including basal and high glucagon phases will measure dynamic metabolic responses and collect lipidomic/metabolomic data. The protocol integrates imaging, tracer kinetics, and molecular profiling to characterize a potential glucagon-resistant phenotype in humans with T2DM and MASLD.
Who should consider this trial
Good fit: Adults with type 2 diabetes diagnosed at least six months earlier, BMI >26 kg/m², able to travel to Aarhus, and either meeting MR-spectroscopy liver fat >5.6% for the MASLD group or lacking MASLD for the comparator group.
Not a fit: People with severely uncontrolled diabetes (HbA1c ≥100 mmol/mol), low C-peptide (<200 pmol/L), current insulin or other excluded medications, active smoking, recent cancer, pregnancy, or recent radioactive isotope exposure are unlikely to qualify or benefit.
Why it matters
Potential benefit: If successful, the trial could identify glucagon resistance as a mechanism driving liver fat in people with type 2 diabetes and point to new treatment targets.
How similar studies have performed: Animal and some human studies support a role for glucagon in hepatic lipid metabolism, but comprehensive human protocols combining tracer infusions, PET-CT, and lipidomics to define glucagon resistance remain limited.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Aarhus
- Aarhus University Hospital — Aarhus, Denmark (Recruiting)
Study contacts
- Study coordinator: Kia E. Fonfara, Medical Doctor
- Email: kia.eistrup@clin.au.dk
- Phone: +4524607114
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.