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| Name | Class |
|---|---|
| dsm-firmenich Switzerland AG | INDUSTRY |
| Diabetes Fonds | OTHER |
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The main objective of the study is to investigate if resveratrol supplementation can improve overall and muscle-specific insulin sensitivity in first-degree relatives of type 2 diabetic patients.
As a secondary objective the investigators want to investigate whether the improved insulin sensitivity can be attributed to improved muscle mitochondrial oxidative capacity and a reduced intrahepatic and cardiac lipid content. Furthermore, in a subset of the participants the investigators want to investigate the effect of resveratrol on glucose uptake in brown adipose tissue.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| resveratrol | Active Comparator | resveratrol will be given for 30 or 34 days (if included in brown adipose tissue measurement), twice daily. One pill, which contains 75 mg of resveratrol, will be provided with lunch, and the other pill of 75 mg will be provided with dinner. So in total 150 mg/day of resveratrol will be given. |
|
| placebo | Placebo Comparator | A placebo will be given for 30 or 34 days (if included in brown adipose tissue measurement), twice daily. One pill will be provided with lunch and the other pill will be provided with dinner. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo | Dietary Supplement | A placebo will given for 30 days or 34 days (if included in brown adipose tissue measurement), twice daily. One pill will be provided with lunch, and the other pill will be provided with dinner. |
| Measure | Description | Time Frame |
|---|---|---|
| insulin sensitivity: overall, muscle- and liver specific | Hyperinsulinemic euglycemic clamp combined with indirect calorimetry: Glucose infusion rate (GIR), rate of appearance and disappearance of glucose (Ra, Rd), endogenous glucose production (EGP), oxidative and non-oxidative glucose disposal, carbohydrate and lipid oxidation, energy expenditure. | 30 days after supplementation |
| Measure | Description | Time Frame |
|---|---|---|
| muscle mitochondrial oxidative capacity (in vivo and ex vivo) | In vivo: Phosphocreatine levels will be measured by P-MRS (before, during, and after exercise) as a marker for in vivo mitochondrial function in the vastus lateralis muscle. Ex vivo mitochondrial function in skeletal muscle will be measured by oxygen consumption in muscle fibres (muscle biopsy) on lipid-derived and carbohydrate-derived substrates. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximal aerobic capacity (VO2max) | 27 days after supplementation | |
| Blood pressure | 30 days after supplementation |
Inclusion Criteria:
Exclusion Criteria:
Use of anticoagulants
Uncontrolled hypertension
Haemoglobin <7.8 mmol/l
In case of an abnormal ECG in rest: this will be discussed with the responsible medical doctor
HBA1C > 6.5%
Diagnosed with type 2 diabetes
Medication use known to interfere with glucose homeostasis/metabolism
Current alcohol consumption > 20 grams/day
Subjects who don't want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed, cannot participate in the study.
Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention.
Participation in another biomedical study within 1 month before the first screening visit
Any condition, disease or abnormal laboratory test result that, in the opinion of the Investigator, would interfere with the study outcome, affect trial participation or put the subject at undue risk
Any contra-indication to MRI scanning. These contra-indications include patients with following devices:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Schrauwen, PhD | Maastricht University Medical Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University Medical Centre | Maastricht | Limburg | 6200 MD | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29706321 | Derived | de Ligt M, Bruls YMH, Hansen J, Habets MF, Havekes B, Nascimento EBM, Moonen-Kornips E, Schaart G, Schrauwen-Hinderling VB, van Marken Lichtenbelt W, Schrauwen P. Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes. Mol Metab. 2018 Jun;12:39-47. doi: 10.1016/j.molmet.2018.04.004. Epub 2018 Apr 18. |
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| ID | Term |
|---|---|
| D018149 | Glucose Intolerance |
| D003920 | Diabetes Mellitus |
| D003924 | Diabetes Mellitus, Type 2 |
| D007333 | Insulin Resistance |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |
| ID | Term |
|---|---|
| D006943 | Hyperglycemia |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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| resveratrol | Dietary Supplement | resveratrol will be given for 30 days or 34 days (if included in brown adipose tissue measurement), twice daily. One pill, which contains 75 mg of resveratrol, will be provided with lunch, and the other pill, also containing 75 mg will be given with dinner. So in total a dose of 150 mg/day will be given. |
|
|
| 30 days after supplementation |
| intramyocellular lipid content | Skeletal muscle lipid accumulation measured by immunohistochemistry in muscle biopsy from vastus lateralis muscle | 30 days after supplementation |
| intrahepatic lipid content | Intrahepatic lipid content measured with H-MRS | 30 days after supplementation |
| intracardiac lipid content | Intracardiac lipid content measured with H-MRS | 30 days after supplementation |
| heart function | Cardiac function: diastolic and systolic heart function will be measured with ultrasound | 30 days after supplementation |
| brown adipose tissue activity | subjects will be exposed to an individualized cooling protocol, after which an 18F-FDG PET/CT scan is made | 34 days after supplementation |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |