Depletion of Liver Fat in Type 2 Diabetes

Summary

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

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

Conditions4

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