Lowering liver fat in people with type 2 diabetes
A Parallel Group Randomized Trial Investigating the Effect of Hepatic Fat Depletion Via a Very-low Calorie Diet on Hepatokine Secretion and Function in People With Type 2 Diabetes
This trial will try a two-week very-low-calorie diet to see if lowering liver fat restores exercise-induced FGF21 secretion in people with type 2 diabetes.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 42 (estimated) |
| Ages | 30 Years to 70 Years |
| Sex | All |
| Sponsor | Rigshospitalet, Denmark Academic / other |
| Locations | 1 site (Copenhagen, Capital Region) |
| Trial ID | NCT06211556 on ClinicalTrials.gov |
What this trial studies
This parallel randomized trial will enroll 42 adults with type 2 diabetes and obesity to test whether a two-week very-low-calorie diet (~800 kcal/day) reduces liver fat and restores exercise-induced FGF21 secretion. Participants will have baseline and post-intervention MRI liver fat measurements, exercise testing with serial FGF21 sampling after about one hour of cycling at 60% VO2peak, body composition, and cardiometabolic blood markers. Participants are randomized to the VLCD or a free-living control group and changes from before to after the two-week period will be compared between groups. Secondary analyses will examine links between liver fat loss, adiponectin, and other metabolic outcomes.
Who should consider this trial
Good fit: Adults aged 30–70 with type 2 diabetes diagnosed less than 7 years, BMI 30–40 kg/m2, inactive, and managing glucose with diet or metformin are the ideal candidates.
Not a fit: People taking glucose‑lowering medications other than metformin, those with very high HbA1c, long-standing diabetes, or BMI outside 30–40 kg/m2 are unlikely to be eligible or to benefit.
Why it matters
Potential benefit: If successful, lowering liver fat could restore beneficial exercise-driven FGF21 signaling and improve insulin sensitivity and metabolic health.
How similar studies have performed: Short-term very-low-calorie diets have previously reduced liver fat and improved metabolic markers, but restoring exercise-induced FGF21 secretion in type 2 diabetes is relatively novel and unproven.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Men and women 30-70 years of age * The target population is persons with type 2 diabetes. I.e., persons are eligible if they are diagnosed with type 2 diabetes either only with metformin for managing glucose or without use of glucose lowering medications. Persons with a HbA1c ≥ 48 mmol/mol with or without the use of glucose lowering medications are also eligible. Any glucose lowering medications other than metformin are disallowed (described under "Exclusion criteria, below) * Diabetes duration \< 7 years * Body Mass Index (BMI) ≥ 30 kg/m2 and ≤ 40 kg/m2 * Accepts medical regulation by the study endocrinologist * Inactivity, defined as \< 1,5 hours of structured physical activity pr. week at moderate intensity and cycling \< 30 minutes/5 km pr. day at moderate intensity (moderate intensity = out of breath but able to speak) Exclusion Criteria: * HbA1c ≥ 75 mmol/mol with no glucose lowering medications * HbA1c ≥ 64 mmol/mol with mono glucose lowering therapy (if compliant with the prescription) * HbA1c ≥ 57 mmol/mol with ≥ dual glucose lowering therapy (if compliant with the prescription) * Diagnosis of Type 1 diabetes, MODY-diabetes, Type 1½ diabetes or LADA-diabetes * eGFR\<60mL/min (assessed via screening blood sample) * Treatment with any glucose-lowering medications other than metformin (e.g., insulin (long and/or short acting), sulphonylurea based drugs, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter-2 inhibitors, thiazolidinediones, alpha-glucosidase inhibitors) * Presence of metal in the body that would contraindicate an MRI scan * Known or signs of intermediate or severe microvascular complications to diabetes (retino-, neuro- or nephropathy) * Known cancer * Lung disease, other than asthma that can be managed with beta2-agonists and does not exhibit seasonal variation * Known cardiovascular disease * Known hyperthyroid disease * Clinical or biochemical signs of hypothyroid disease * Changes in hypothyroid disease treatment within the last 3 three months prior to enrolment * Known liver disease - defined as ALAT or ASAT elevated three times above upper limit * Known autoimmune disease * Psoriasis disease requiring systemic treatment or cutan elements bigger than a total area of 25 cm2 * Other endocrine disorder causing obesity * Current treatment with anti-obesity medication * Current treatment with anti-inflammatory medication * Weight loss of \> 5kg within the last 6 months * Changes in symptoms or anti-depressive medication three months prior to enrolment * Diagnosis of psychiatric disorder or treatment with anti-psychotic medication * History of suicidal behavior or ideations within the last three months prior enrolment * Previous surgical treatment for obesity (excluding liposuction \> 1 year prior to enrolment) * Pregnant/considering pregnancy, or lactating * Functional impairments that prevent the performance of intensive exercise * Participation in other research intervention studies * Macroalbuminuria at pre-screening (assessed via screening blood sample) * Biochemical sign of other major diseases * Presence of circulating glutamatdecarboxylase anti body (GAD) 65 (assessed via screening blood sample) * Objective findings that contraindicate participation in intensive exercise * Incidental findings that contraindicate participation in the study * Unable to allocate the needed time to fulfill the intervention * Language barrier, mental incapacity, unwillingness, or inability to understand and be able to complete the interventions
Where this trial is running
Copenhagen, Capital Region
- Rigshospitalet - CFAS — Copenhagen, Capital Region, Denmark (Recruiting)
Study contacts
- Principal investigator: Cody G Durrer, Ph.D. — Center for Aktiv Sundhed - Rigshospitalet
- Study coordinator: Cody G Durrer, Ph.D.
- Email: cody.garett.durrer@regionh.dk
- Phone: +4550104538
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.