Insulin Resistance, Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Diseases, Diabetes Mellitus, Endocrine System Diseases, Resveratrol, Therapeutic Uses
Brief summary
Resveratrol is a natural polyphenol (a compound containing a phenol functional group) that can be found in many plants. The purpose of this research is to study the effects of resveratrol on the action of insulin (a hormone produced in the body by the pancreas that regulates the amount of sugar in the blood), fat accumulation, and inflammation in the body.
Detailed description
Participants will meet with the study team to discuss dietary recommendations. Each participant will be instructed to follow a standardized diet plan and to avoid vigorous exercise before beginning the study. Participants will be given a 28 day supply of resveratrol capsules (Two 500 mg capsules taken twice a day). A comprehensive study of whole-body insulin action called a pancreatic clamp will be done and small samples of fat and muscle will be taken before and after the administration of resveratrol.
Interventions
DRUGResveratrol
1,000mg twice daily for 28 days
Sponsors
Albert Einstein College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI: 26-35 * Non-smoker * Normal screening labs (CMC, chemistry, LFTs PT/PTT) * No CAD * Good IV access
Exclusion criteria
* High cholesterol * \<4 week history of participation in another drug trial * Severe hypertension * Heart disease * Liver disease of liver abnormalities * Cerebrovascular disease, i.e. stroke * CVD * Seizures * Bleeding disorders * Muscle disease * Cancer * HIV * Hepatitis (all types) * Mentally disabled persons * Pregnant women * Allergies to Novocaine, Lidocaine, Benzocaine * Subjects on the following medications: * Anticoagulant and antiplatelet drugs * Anti-epileptic drugs * Mexiletene * Quinidine * Cyclosporine * Tacrolimus * HIV protease inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peripheral Insulin Sensitivity (RD) Measured by the Change in Glucose Rates of Disappearance With Resveratrol or Placebo at Baseline and at 4 Weeks. | 4 weeks | We will measure peripheral insulin sensitivity by determining the rate of glucose uptake (RD). RD will be measured using a 6 hours stepped pancreatic clamp study procedure under various treatment conditions (eg, resveratrol or placebo). by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endogenous Glucose Production (EGP), With Resveratrol or Placebo at Baseline and at 4 Weeks. | 4 weeks | Endogenous glucose production will be used to determine hepatic insulin sensitivity. Rates of EGP (a measure of the body's production of sugar) will be measured using a 6 hour stepped pancreatic clamp procedure under various treatment conditions (eg, resveratrol or placebo), by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar). |
| Effects of Resveratrol on Skeletal Muscle Mitochondrial Numbers | 4 weeks | Skeletal muscle mitochondria numbers were calculated under EM on subjects pre- and post- treatment of either Resveratrol or placebo intervention. |
| Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | 4 weeks | Changes of relative copy number of gene inflammatory markers in whole fat tissue were studied by quantitative, real-time RT-PCR, resveratrol vs. placebo |
| Muscle Mitochondrial Area | 4 Weeks | Skeletal Muscle Mitochondria Area Before and After 4 Weeks of Resveratrol/Placebo Treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Resveratrol Each participant received a supply of resveratrol (1,000mg) twice daily for 28 days | 12 |
| Placebo Each participant received a supply of placebo (similar in taste and appearance to Resveratrol) twice daily for 28 days | 8 |
| Total | 20 |
Baseline characteristics
| Characteristic | Resveratrol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.75 years STANDARD_DEVIATION 10.5 | 52.88 years STANDARD_DEVIATION 5.44 | 51.6 years STANDARD_DEVIATION 8.71 |
| Ethnicity (NIH/OMB) Ethnicity Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Ethnicity Not Hispanic or Latino | 11 Participants | 6 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Ethnicity Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 12 participants | 8 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 8 |
| other Total, other adverse events | 3 / 12 | 0 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 |
Outcome results
Primary
Peripheral Insulin Sensitivity (RD) Measured by the Change in Glucose Rates of Disappearance With Resveratrol or Placebo at Baseline and at 4 Weeks.
We will measure peripheral insulin sensitivity by determining the rate of glucose uptake (RD). RD will be measured using a 6 hours stepped pancreatic clamp study procedure under various treatment conditions (eg, resveratrol or placebo). by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar).
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Resveratrol | Peripheral Insulin Sensitivity (RD) Measured by the Change in Glucose Rates of Disappearance With Resveratrol or Placebo at Baseline and at 4 Weeks. | RD at baseline | 6.573 mg/kg/min | Standard Deviation 1.709 |
| Resveratrol | Peripheral Insulin Sensitivity (RD) Measured by the Change in Glucose Rates of Disappearance With Resveratrol or Placebo at Baseline and at 4 Weeks. | RD at 4 weeks | 8.445 mg/kg/min | Standard Deviation 3.616 |
| Placebo | Peripheral Insulin Sensitivity (RD) Measured by the Change in Glucose Rates of Disappearance With Resveratrol or Placebo at Baseline and at 4 Weeks. | RD at baseline | 7.272 mg/kg/min | Standard Deviation 2.81 |
| Placebo | Peripheral Insulin Sensitivity (RD) Measured by the Change in Glucose Rates of Disappearance With Resveratrol or Placebo at Baseline and at 4 Weeks. | RD at 4 weeks | 7.419 mg/kg/min | Standard Deviation 2.785 |
Secondary
Effects of Resveratrol on Skeletal Muscle Mitochondrial Numbers
Skeletal muscle mitochondria numbers were calculated under EM on subjects pre- and post- treatment of either Resveratrol or placebo intervention.
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Resveratrol | Effects of Resveratrol on Skeletal Muscle Mitochondrial Numbers | Baseline_mitochondria number | 48.489 mitochondria number | Standard Deviation 13.18 |
| Resveratrol | Effects of Resveratrol on Skeletal Muscle Mitochondrial Numbers | 4 weeks_mitochondria number | 46.622 mitochondria number | Standard Deviation 18.895 |
| Placebo | Effects of Resveratrol on Skeletal Muscle Mitochondrial Numbers | 4 weeks_mitochondria number | 48.850 mitochondria number | Standard Deviation 14.632 |
| Placebo | Effects of Resveratrol on Skeletal Muscle Mitochondrial Numbers | Baseline_mitochondria number | 41.275 mitochondria number | Standard Deviation 10.826 |
Secondary
Endogenous Glucose Production (EGP), With Resveratrol or Placebo at Baseline and at 4 Weeks.
Endogenous glucose production will be used to determine hepatic insulin sensitivity. Rates of EGP (a measure of the body's production of sugar) will be measured using a 6 hour stepped pancreatic clamp procedure under various treatment conditions (eg, resveratrol or placebo), by monitoring changes in the level of a non-radioactive, naturally occurring form of glucose (sugar).
Time frame: 4 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Resveratrol | Endogenous Glucose Production (EGP), With Resveratrol or Placebo at Baseline and at 4 Weeks. | EGP at baseline | 1.014 mg/kg/min | Standard Deviation 0.353 |
| Resveratrol | Endogenous Glucose Production (EGP), With Resveratrol or Placebo at Baseline and at 4 Weeks. | EGP at 4 weeks | 1.140 mg/kg/min | Standard Deviation 0.525 |
| Placebo | Endogenous Glucose Production (EGP), With Resveratrol or Placebo at Baseline and at 4 Weeks. | EGP at baseline | 0.903 mg/kg/min | Standard Deviation 0.436 |
| Placebo | Endogenous Glucose Production (EGP), With Resveratrol or Placebo at Baseline and at 4 Weeks. | EGP at 4 weeks | 1.552 mg/kg/min | Standard Deviation 0.962 |
Secondary
Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks
Changes of relative copy number of gene inflammatory markers in whole fat tissue were studied by quantitative, real-time RT-PCR, resveratrol vs. placebo
Time frame: 4 weeks
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Resveratrol | Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | TNFa_Whole adipose tissue | 0.47 Ratio | Standard Deviation 0.21 |
| Resveratrol | Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | IL6_Whole adipose tissue | 1.84 Ratio | Standard Deviation 3.59 |
| Resveratrol | Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | PAI-1_Whole adipose tissue | 0.56 Ratio | Standard Deviation 0.16 |
| Placebo | Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | TNFa_Whole adipose tissue | 1.4 Ratio | Standard Deviation 0.82 |
| Placebo | Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | IL6_Whole adipose tissue | 1.68 Ratio | Standard Deviation 1.3 |
| Placebo | Gene Expression in Whole Fat Tissue , Before and After 4 Weeks' Resveratrol and Placebo. Ratio From Baseline Versus at 4 Weeks | PAI-1_Whole adipose tissue | 0.76 Ratio | Standard Deviation 0.25 |
Secondary
Muscle Mitochondrial Area
Skeletal Muscle Mitochondria Area Before and After 4 Weeks of Resveratrol/Placebo Treatment
Time frame: 4 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Resveratrol | Muscle Mitochondrial Area | Baseline_mitochondria area | 0.070 µm² | Standard Deviation 0.021 |
| Resveratrol | Muscle Mitochondrial Area | 4 weeks_mitochondria area | 0.098 µm² | Standard Deviation 0.039 |
| Placebo | Muscle Mitochondrial Area | Baseline_mitochondria area | 0.080 µm² | Standard Deviation 0.026 |
| Placebo | Muscle Mitochondrial Area | 4 weeks_mitochondria area | 0.102 µm² | Standard Deviation 0.02 |