type 2 diabetes sodium phenyl butyrate insulin resistance branched-chain amino acids mitochondrial function energy metabolism
Conditions
Interventions
2 weeks oral administration of 4.8 g/m2/day Pheburane or placebo per day, depending on body surface area. Pheburane needs to be administered spread over the day in 3 times taken with a meal.
Sponsors
Maastricht UniversityNUTRIMUniversiteitssingel 406229 ER Maastricht+31 43 3881476secretariaat-nutrim@maastrichtuniversity.nl
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients are able to provide signed and dated written informed consent prior to any study specific procedures 2. Women are post-menopausal (defined as at least 1 year post cessation of menses) and aged =45 and =75 years. Males are aged =40 years and =75 years 3. Patients should have suitable veins for cannulation or repeated venipuncture 4. Caucasians 5. BMI: 25-38 kg/m2 6. Diagnosed with T2D at least 1.5 years before the start of the study 7. Relatively well-controlled T2D: HbA1c < 8.5% 8. Oral glucose lowering medication: metformin only or in combination with sulfonylurea agents and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months 9. No signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy 10. No signs of active liver or kidney malfunction
Exclusion criteria
Exclusion criteria: 1. Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator 2. Participate in physical activity more than 3 times a week 3. Unstable body weight (weight gain or loss > 5 kg in the last three months) 4. Insulin dependent T2D 5. Patients with congestive heart failure and and/or severe renal and or liver insufficiency or known sodium retention with oedema 6. Patients using Probalan (probenecid), Haldol (haloperidol), Depakene (valproate) or medical products containing corticosteroids 7. Men: Hb <8.4 mmol/L, Women: Hb <7.8 mmol/l 8. Any contra-indication MRI scanning. These contra-indications include patients with e.g. the following: • Central nervous system aneurysm clip • Implanted neural stimulator • Implanted cardiac pacemaker of defibrillator • Cochlear implant • Metal containing corpora aliena in the eye or brains
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective is the delta change in whole body insulin sensitivity expressed as glucose disposal rate (µmol/kg/min) upon 2 weeks of Na-PB vs. placebo treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| • muscle mitochondrial function upon 2 days and 2 weeks treatment periods expressed as O2-flux in pmol/mg/s • whole-body energy metabolism upon 2 days and 2 weeks treatment periods expressed as respiratory exchange ratio (RER) and kJ/kg/min • fat accumulation in muscle and the liver expressed as % upon 2 days and 2 weeks treatment periods | — |
Contacts
Public ContactE. Phielix
Maastricht University Department of Nutrition and Movement Sciences
Outcome results
None listed