Metabolic Syndrome X
Conditions
Keywords
metabolic syndrome, central obesity, resveratrol, insulin secretion, insulin sensitivity
Brief summary
The Metabolic Syndrome is a high prevalence disease worldwide. About a quarter of the adult population suffers the disease. Resveratrol is a substance found in many plants, including grapes, nuts and wine, but it's also found in Polygonum cuspidatum. There is evidence that resveratrol consumption has beneficial effects on glucose and lipids metabolism, blood pressure and body weight. The aim of this study was to evaluate the effect of resveratrol on metabolic syndrome, insulin sensitivity and insulin secretion. The investigators hypothesis was that the administration of resveratrol modifies the metabolic syndrome, insulin sensitivity and insulin secretion.
Detailed description
A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with a diagnosis of metabolic syndrome in accordance with the International Diabetes Federation (IDF). Waist circumference, glucose, insulin levels, lipid profile, creatinine and acid uric were evaluated after a 75 g of dextrose load. 12 received resveratrol, 500 mg, three times per day (1500 mg) before meals during 3 months. The remaining 12 patients received placebo with the same prescription. Area Under the Curve of glucose and insulin was calculated as well as total insulin secretion (insulinogenic index), first-phase of insulin secretion (Stumvoll index) and insulin sensitivity (Matsuda index). This protocol was approved by a local ethics committee and written informed consent was obtained from all volunteers. Results are presented as mean and standard deviation. Intra and inter group differences were tested using the Wilcoxon signed-rank and Mann-Whitney U-test respectively; p≤0.05 was considered significant.
Interventions
DRUGResveratrol
Resveratrol capsules of 500 mg three times per day before meals with a total dosis of 1500 mg per day.
DRUGPlacebo
Calcined magnesia capsules, 500 mg, three times per day before meals with a total dose per day of 1500 mg
Sponsors
University of Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Patients both sexes * Age between 30 and 50 years * Metabolic Syndrome according to the IDF criteria * Waist circumference * Man ≥90 cm * Woman ≥80 cm * And two of the following criteria: * High density lipoprotein * Man ≤40 mg/dL * Woman ≤50 mg/dL * Fasting glucose ≥100 mg/dL * Triglycerides ≥150 mg/dL * Blood pressure ≥130/85 mmHg * Informed consent signed
Exclusion criteria
* Women with confirmed or suspected pregnancy * Women under lactation and/or puerperium * Hypersensibility to resveratrol * Physical impossibility for taking pills * Known uncontrolled renal, hepatic, heart or thyroid diseased * Previous treatment for the metabolic syndrome components * Body Mass Index ≥39.9 kg/m2 * Fasting glucose ≥126 mg/dL * Triglycerides ≥500 mg/dL * Total cholesterol ≥240 mg/dL * Low density lipoprotein (c-LDL) ≥190 mg/dL * Blood Pressure ≥140/90 mmHg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diastolic Blood Pressure at Week 12 | Week 12 | The diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the diastolic blood pressure at week 12 |
| Fasting Glucose Levels at Week 12. | Week 12 | The fasting glucose levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12 |
| Systolic Blood Pressure at Week 12. | Week 12 | The systolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the systolic blood pressure at week 12 |
| First Phase of Insulin Secretion at Week 12. | Week 12 | The first phase of insulin secretion was calculated at baseline and week 12 with Stumvoll index and the entered values reflect the first phase of insulin secretion at week 12 |
| Total Insulin Secretion at Week 12. | Week 12 | The total insulin secretion was calculated at baseline and week 12 with insulinogenic index and the entered values reflect the total insulin secretion at week 12 |
| Total Insulin Sensitivity at Week 12. | Week 12 | The insulin sensitivity was calculated at baseline and week 12 with Matsuda index and the entered values reflect the insulin sensitivity at week 12 |
| Waist Circumference at Week 12 | Week 12 | Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflect the waist circumference measure at week 12 |
| Triglycerides Levels at Week 12 | Week 12 | The triglycerides were evaluated at baseline and week 12 with enzymatic-colorimetric techniques and the entered values reflect the triglycerides level at week 12 |
| High Density Lipoprotein (c-HDL) Levels at Week 12. | Baseline. Week 12 | The c-HDL levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index at Week 12 | Week 12 | The Body Mass index was calculated at baseline and at week 12 with the Quetelet index and the entered values reflect the body mass index at week 12 |
| Total Cholesterol at Week 12 | Week 12 | The total cholesterol was estimated by standardized techniques at baseline and week 12 and the entered values reflect the total cholesterol level at week 12 |
| Low Density Lipoproteins (c-LDL) at Week 12 | Week 12 | The c-LDL levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the c-LDL levels at week 12 |
| Creatinine at Week 12. | Baseline. Week 12. | The creatinine levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the creatinine levels at week 12 |
| Uric Acid at Week 12. | Week 12. | The uric acid levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the uric acid levels at week 12 |
| Weight at Week 12. | Week 12 | The weight was measured at baseline, week 4, week 8 and week 12 with a bioimpedance balance and the entered values reflect the weight at week 12 |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Resveratrol Resveratrol capsules, 500 mg, three times per day before meals during 90 days
Resveratrol: Resveratrol capsules of 500 mg three times per day before meals with a total dosis of 1500 mg per day. | 12 |
| Placebo Calcined magnesia capsules, 500 mg, three times per day before meals during 90 days
Placebo: Calcined magnesia capsules, 500 mg, three times per day before meals with a total dose per day of 1500 mg | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | Resveratrol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.75 years STANDARD_DEVIATION 5.38 | 40.33 years STANDARD_DEVIATION 5.41 | 40.04 years STANDARD_DEVIATION 5.29 |
| AUC glucose | 935.8 mmol*h/L STANDARD_DEVIATION 188.6 | 950.8 mmol*h/L STANDARD_DEVIATION 167.6 | 943.3 mmol*h/L STANDARD_DEVIATION 174.6 |
| AUC insuline | 48418.5 pmol*h/L STANDARD_DEVIATION 22707.4 | 62955.8 pmol*h/L STANDARD_DEVIATION 37620 | 55687.1 pmol*h/L STANDARD_DEVIATION 31282.6 |
| Body mass index (BMI) | 35.56 kg/m2 STANDARD_DEVIATION 3.2 | 33.73 kg/m2 STANDARD_DEVIATION 3.7 | 34.65 kg/m2 STANDARD_DEVIATION 3.5 |
| Body weight | 94.4 kg STANDARD_DEVIATION 13.2 | 91.0 kg STANDARD_DEVIATION 10.7 | 92.71 kg STANDARD_DEVIATION 11.9 |
| Cholesterol | 206.0 mg/dL STANDARD_DEVIATION 32 | 195.4 mg/dL STANDARD_DEVIATION 34.8 | 200.7 mg/dL STANDARD_DEVIATION 33.1 |
| Diastolic blood pressure | 78.36 mmHg STANDARD_DEVIATION 8.7 | 77.15 mmHg STANDARD_DEVIATION 8.4 | 77.76 mmHg STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Fat Mass | 41.18 kg STANDARD_DEVIATION 7.9 | 36.13 kg STANDARD_DEVIATION 9.2 | 38.66 kg STANDARD_DEVIATION 8.8 |
| First phase of insulin secretion | 1256.6 index STANDARD_DEVIATION 601.5 | 1440.0 index STANDARD_DEVIATION 619.8 | 1348.3 index STANDARD_DEVIATION 604.6 |
| Glucose 0' | 4.8 mmol/l STANDARD_DEVIATION 0.6 | 5.1 mmol/l STANDARD_DEVIATION 0.4 | 4.95 mmol/l STANDARD_DEVIATION 0.5 |
| Glucose 120' | 6.5 mmol/l STANDARD_DEVIATION 1.7 | 6.9 mmol/l STANDARD_DEVIATION 2.2 | 6.7 mmol/l STANDARD_DEVIATION 1.9 |
| Glucose 30' | 8.5 mmol/l STANDARD_DEVIATION 1.8 | 8.4 mmol/l STANDARD_DEVIATION 1.1 | 8.4 mmol/l STANDARD_DEVIATION 1.4 |
| Glucose 60' | 9.0 mmol/l STANDARD_DEVIATION 2.7 | 9.3 mmol/l STANDARD_DEVIATION 1.8 | 9.1 mmol/l STANDARD_DEVIATION 2.2 |
| Glucose 90' | 8.3 mmol/l STANDARD_DEVIATION 2.3 | 8.0 mmol/l STANDARD_DEVIATION 1.8 | 8.2 mmol/l STANDARD_DEVIATION 2 |
| HDL-c | 37.3 mg/dL STANDARD_DEVIATION 3.7 | 37.9 mg/dL STANDARD_DEVIATION 7.7 | 37.6 mg/dL STANDARD_DEVIATION 5.9 |
| Height | 162.67 cm STANDARD_DEVIATION 7.2 | 164.33 cm STANDARD_DEVIATION 7.2 | 163.50 cm STANDARD_DEVIATION 7.1 |
| Insulin sensitivity | 3.5 index STANDARD_DEVIATION 1.5 | 3.3 index STANDARD_DEVIATION 1.5 | 3.4 index STANDARD_DEVIATION 1.4 |
| LDL-c | 120.7 mg/dL STANDARD_DEVIATION 32 | 119.8 mg/dL STANDARD_DEVIATION 46.5 | 120.2 mg/dL STANDARD_DEVIATION 39 |
| Region of Enrollment Mexico | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 17 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
| Systolic blood pressure | 119.96 mmHg STANDARD_DEVIATION 13.1 | 116.03 mmHg STANDARD_DEVIATION 13.2 | 117.99 mmHg STANDARD_DEVIATION 13 |
| Total insulin secretion | 0.48 index STANDARD_DEVIATION 0.22 | 0.59 index STANDARD_DEVIATION 0.29 | 0.54 index STANDARD_DEVIATION 0.26 |
| Triglycerides | 254.3 mg/dL STANDARD_DEVIATION 55.6 | 233.8 mg/dL STANDARD_DEVIATION 77.7 | 244.0 mg/dL STANDARD_DEVIATION 66.9 |
| Waist circumference | 109.83 cm STANDARD_DEVIATION 9.3 | 104.50 cm STANDARD_DEVIATION 8.5 | 107.17 cm STANDARD_DEVIATION 9.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 12 | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Diastolic Blood Pressure at Week 12
The diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the diastolic blood pressure at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Diastolic Blood Pressure at Week 12 | 78.1 mmHg | Standard Deviation 9.2 |
| Placebo | Diastolic Blood Pressure at Week 12 | 78.9 mmHg | Standard Deviation 7.5 |
p-value: 0.672Wilcoxon (Mann-Whitney)
Primary
Fasting Glucose Levels at Week 12.
The fasting glucose levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Fasting Glucose Levels at Week 12. | 4.6 mmol/L | Standard Deviation 0.6 |
| Placebo | Fasting Glucose Levels at Week 12. | 4.5 mmol/L | Standard Deviation 0.5 |
p-value: 0.07Wilcoxon (Mann-Whitney)
Primary
First Phase of Insulin Secretion at Week 12.
The first phase of insulin secretion was calculated at baseline and week 12 with Stumvoll index and the entered values reflect the first phase of insulin secretion at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | First Phase of Insulin Secretion at Week 12. | 1019.7 index | Standard Deviation 335.1 |
| Placebo | First Phase of Insulin Secretion at Week 12. | 1279.3 index | Standard Deviation 599.2 |
p-value: 0.278Wilcoxon (Mann-Whitney)
Primary
High Density Lipoprotein (c-HDL) Levels at Week 12.
The c-HDL levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12
Time frame: Baseline. Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | High Density Lipoprotein (c-HDL) Levels at Week 12. | 37.6 mg/dL | Standard Deviation 5 |
| Placebo | High Density Lipoprotein (c-HDL) Levels at Week 12. | 41.1 mg/dL | Standard Deviation 8.8 |
p-value: 0.859Wilcoxon (Mann-Whitney)
Primary
Systolic Blood Pressure at Week 12.
The systolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the systolic blood pressure at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Systolic Blood Pressure at Week 12. | 116.1 mmHg | Standard Deviation 11.3 |
| Placebo | Systolic Blood Pressure at Week 12. | 121.7 mmHg | Standard Deviation 11 |
p-value: 0.338Wilcoxon (Mann-Whitney)
Primary
Total Insulin Secretion at Week 12.
The total insulin secretion was calculated at baseline and week 12 with insulinogenic index and the entered values reflect the total insulin secretion at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Total Insulin Secretion at Week 12. | .28 index | Standard Deviation 0.08 |
| Placebo | Total Insulin Secretion at Week 12. | .60 index | Standard Deviation 0.3 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Primary
Total Insulin Sensitivity at Week 12.
The insulin sensitivity was calculated at baseline and week 12 with Matsuda index and the entered values reflect the insulin sensitivity at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Total Insulin Sensitivity at Week 12. | 4.2 index | Standard Deviation 1.2 |
| Placebo | Total Insulin Sensitivity at Week 12. | 4.7 index | Standard Deviation 2.4 |
p-value: 0.083Wilcoxon (Mann-Whitney)
Primary
Triglycerides Levels at Week 12
The triglycerides were evaluated at baseline and week 12 with enzymatic-colorimetric techniques and the entered values reflect the triglycerides level at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Triglycerides Levels at Week 12 | 210.6 mg/dL | Standard Deviation 63.3 |
| Placebo | Triglycerides Levels at Week 12 | 235.8 mg/dL | Standard Deviation 148.5 |
p-value: 0.131Wilcoxon (Mann-Whitney)
Primary
Waist Circumference at Week 12
Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflect the waist circumference measure at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Waist Circumference at Week 12 | 105.4 cm | Standard Deviation 10.7 |
| Placebo | Waist Circumference at Week 12 | 105.8 cm | Standard Deviation 7.2 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Body Mass Index at Week 12
The Body Mass index was calculated at baseline and at week 12 with the Quetelet index and the entered values reflect the body mass index at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Body Mass Index at Week 12 | 34.3 kg/m2 | Standard Deviation 3 |
| Placebo | Body Mass Index at Week 12 | 34.0 kg/m2 | Standard Deviation 3.6 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Creatinine at Week 12.
The creatinine levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the creatinine levels at week 12
Time frame: Baseline. Week 12.
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Creatinine at Week 12. | 57.94 µmol/l | Standard Deviation 14.2 |
| Placebo | Creatinine at Week 12. | 63.29 µmol/l | Standard Deviation 11.07 |
p-value: 0.557Wilcoxon (Mann-Whitney)
Secondary
Low Density Lipoproteins (c-LDL) at Week 12
The c-LDL levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the c-LDL levels at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Low Density Lipoproteins (c-LDL) at Week 12 | 122.3 mg/dL | Standard Deviation 39.2 |
| Placebo | Low Density Lipoproteins (c-LDL) at Week 12 | 126.8 mg/dL | Standard Deviation 33.7 |
p-value: 0.365Wilcoxon (Mann-Whitney)
Secondary
Total Cholesterol at Week 12
The total cholesterol was estimated by standardized techniques at baseline and week 12 and the entered values reflect the total cholesterol level at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Total Cholesterol at Week 12 | 203.4 mg/dL | Standard Deviation 38 |
| Placebo | Total Cholesterol at Week 12 | 208.9 mg/dL | Standard Deviation 27.1 |
p-value: 0.946Wilcoxon (Mann-Whitney)
Secondary
Uric Acid at Week 12.
The uric acid levels were measured at baseline and at week 12 with standardized techniques and the entered values reflect the uric acid levels at week 12
Time frame: Week 12.
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Uric Acid at Week 12. | 277.93 µmol/l | Standard Deviation 38.72 |
| Placebo | Uric Acid at Week 12. | 364.03 µmol/l | Standard Deviation 67.95 |
p-value: <0.01Wilcoxon (Mann-Whitney)
Secondary
Weight at Week 12.
The weight was measured at baseline, week 4, week 8 and week 12 with a bioimpedance balance and the entered values reflect the weight at week 12
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statistical analysis (intention to treat)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Resveratrol | Weight at Week 12. | 90.5 kg | Standard Deviation 12.3 |
| Placebo | Weight at Week 12. | 93.1 kg | Standard Deviation 9.1 |
p-value: <0.01Wilcoxon (Mann-Whitney)