Depletion of Liver Fat in Type 2 Diabetes

ConditionsType2diabetes Obesity

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age30-70

SponsorRigshospitalet, Denmark

About this trial

The aim of this randomized trial is to determine whether liver fat depletion via a short-term (i.e., two weeks) very-low calorie diet will restore the normal exercise-induced secretion of a signaling protein (fibroblast growth factor 21) from the liver in people living with type 2 diabetes. Participants will have their liver fat, body composition, and various markers of metabolic health assessed and then will be randomized to either the very-low calorie diet intervention or a free-living control group for two weeks. Upon completion of the two-week intervention period, participants will redo all of the pre-intervention assessments. The changes in the assessments from before vs. after the intervention period will be compared between the two intervention groups (i.e., the very-low calorie diet group vs. the free living control group).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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 "

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

Very-low calorie diet
Behavioral
\~800 kcal/day delivered via commercially available diet plan (NUPO).

Treatment groups

42 Participants

are divided into 2 treatment groups

Group A: Very-low calorie dietExperimental treatment 1 intervention

Group B: Free-living controlNo intervention 0 interventions

Trial outcomes

Primary outcomes

Difference in change in FGF21 incremental area-under-the-curve

The difference in change between groups of FGF21 incremental area-under-the-curve in plasma following an exercise bout (continuous cycling at an intensity equivalent to 60% VO2peak for a gross energy expenditure of \~2500 kJ) from baseline to follow-up.

Time frame

4 weeks

Secondary outcomes

Difference in change in fasting plasma FGF21

The difference in change between groups in fasting plasma FGF21 from baseline to follow-up.

Time frame

4 weeks

Difference in change in liver fat fraction

The difference in change between groups in liver fat fraction (assessed via MRI) from baseline to follow-up.

Time frame

4 weeks

Difference in change in fasting and post exercise plasma adiponectin

The difference in change between groups in fasting pre- and post-exercise adiponectin in plasma following an exercise bout from baseline to follow-up.

Time frame

4 weeks

Difference in change in adipose tissue mRNA targets relating to FGF21 signaling

Difference in change between groups in expression of the genes encoding adiponectin, FGFR1c, FGFR3c, and β-Klotho in subcutaneous adipose tissue from baseline to follow-up.

Time frame

4 weeks

Other outcomes

Difference in change in fatty liver index

The difference in change between groups in fatty liver index from baseline to follow-up.

Time frame

4 weeks

Difference in change in hepatic steatosis index

The difference in change between groups in hepatis steatosis index from baseline to follow-up.

Time frame

4 weeks

Difference in change in FIB4 index

The difference in change between groups in FIB4 from baseline to follow-up.

Time frame

4 weeks

Difference in change in hunger

Difference in change between groups in appetite and hunger (assessed via a visual analog scale) from baseline to follow-up. The higher scores indicate greater appetite and hunger compared to lower scores.

Time frame

4 weeks