Resveratrol and First-degree Relatives of Type 2 Diabetic Patients

Not Applicable

Completed

• Conditions: Pre-diabetes
• Interventions: Dietary Supplement: placebo; Dietary Supplement: resveratrol

• Registration Number: NCT02129595
• Lead Sponsor: Maastricht University Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04
• Study First Submitted: 2014-04-24
• Study First Submitted QC: 2014-05-01
• Study First Posted: 2014-05-02
• Status Verified: 2016-08
• Primary Completion: 2017-04
• Study Completion: 2017-07-31
• Last Update Submitted: 2017-08-07
• Last Update Posted: 2017-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

• Male sex
• Age: 40-70 years
• BMI 27-35 kg/m2
• Has first-degree relative(s) diagnosed with type 2 diabetes
• Sedentary
• Not more than 2 hours of sports a week
• No active job that requires strenuous physical activity
• Stable dietary habits: no weight gain or loss > 5kg in the last three months
• Insulin resistant: glucose clearance rate below < 350 ml/kg/min, as determined using OGIS120
• Willingness to abstain from resveratrol-containing food products
• Subjects will only be included when the dependent medical doctor of this study approves participation after evaluating data obtained during screening

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:

  • Central nervous system aneurysm clip
  • Implanted neural stimulator
  • Implanted cardiac pacemaker of defibrillator
  • Cochlear implant
  • Insulin pump
  • Metal containing corpora aliena in the eye or brains

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo	placebo	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.
resveratrol	resveratrol	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.

Primary Outcome Measures

Name	Time	Method
insulin sensitivity: overall, muscle- and liver specific	30 days after supplementation	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.

Secondary Outcome Measures

Name	Time	Method
intramyocellular lipid content	30 days after supplementation	Skeletal muscle lipid accumulation measured by immunohistochemistry in muscle biopsy from vastus lateralis muscle
brown adipose tissue activity	34 days after supplementation	subjects will be exposed to an individualized cooling protocol, after which an 18F-FDG PET/CT scan is made
intrahepatic lipid content	30 days after supplementation	Intrahepatic lipid content measured with H-MRS
heart function	30 days after supplementation	Cardiac function: diastolic and systolic heart function will be measured with ultrasound
muscle mitochondrial oxidative capacity (in vivo and ex vivo)	30 days after supplementation	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.
intracardiac lipid content	30 days after supplementation	Intracardiac lipid content measured with H-MRS

Trial Locations

Locations (1)

Maastricht University Medical Centre; 🇳🇱 Maastricht, Limburg, Netherlands