Metabolic Syndrome
Conditions
Keywords
Gymnema Sylvestre, Insulin Secretion, Insulin Sensitivity, Central Obesity
Brief summary
Gymnema sylvestre has demonstrated promising effects in the treatment of obesity, dyslipidemia, hypertension, insulin secretion, among others. The above mentioned findings show that Gymnema sylvestre has an excellent potential for the prevention and treatment of metabolic syndrome.
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 modify International Diabetes Federation criteria. The patients received 300 mg capsules of Gymnema sylvestre or placebo, two times daily before breakfast and dinner for 90 days. Before and after intervention the investigators evaluated: The components of metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein, fasting glucose and blood pressure), body weight, body mass index, total cholesterol, low-density lipoprotein, very-low-density lipoprotein, creatinine, aspartate transaminase and alanine transaminase. Were calculated: Areas under the curve of glucose and insulin were calculated with de Trapezoidal formula. Total insulin secretion was evaluated with the Insulinogenic index and the insulin sensitivity was estimated using the Matsuda index.
Interventions
DRUGPlacebo
Capsules of 300 mg two times per day before breakfast and dinner a total dose of 600 mg per day. During 90 days.
Capsules of 300 mg of calcined magnesium two times per day before breakfast and dinner a total dose of 600 mg per day. During 90 days.
Sponsors
University of Guadalajara
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Letter of consent and release signed by each patient * Body mass index: 25-34.99 kg/m2 * Body weight without variations above or under 5% during the three months prior to the study * Diagnostic of metabolic syndrome according to the modified International Diabetes Federation definition: Central obesity (defined as waist circumference ≥ 80 cm in women and ≥ 90 cm in men) Plus any two of the following four factors: * Triglycerides: 150-499 mg/dL. * High density lipoprotein: Woman \< 50 mg/dL, man \< 40 mg/dL. * Blood pressure systolic:130-139 mmHg and/or Blood pressure diastolic: 85-89 mmHg * Fasting glucose: 100-125 mg/dL
Exclusion criteria
* Type 1 or 2 diabetes mellitus * Previous pharmacological treatment for components of metabolic syndrome * Mental or physical illness interfering with the study * Thyroid or cardiovascular disease * Pregnant or suspected pregnant women * Woman breastfeeding * Index of body mass: ≥ 35 kg/m2 * Treatments known to affect metabolism of glucose, fats and affecting arterial tension * Patients with hepatic or renal diseases background * Patients diagnosed with kidneys disease * Calcined magnesium intolerance * Gymnema Sylvestre intolerance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | week 12 | The insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. |
| Waist Circumference (WC) | Week 12 | The WC was evaluated after an overnight fast with a flexible tape in the midpoint between the lowest rib and the iliac crest and is expressed in centimeters. |
| Triglycerides (TGs) | week 12 | The blood sample for determining of TGs, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L. |
| High-density Lipoprotein Cholesterol (HDL-C) | Week 12 | The blood sample for determining of HDL-C, was taken after an overnight fast and was evaluated by colorimetric method. The value was expressed on mmol/L. |
| Fasting Plasma Glucose (FPG) | week 12 | The blood sample for determining of FPG, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L. |
| Systolic Blood Pressure (SBP) | week 12 | The SBP was evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of SBP. The value was expressed on mmHg. |
| Diastolic Blood Pressure (DBP) | week 12 | The DBP was evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of DBP. The value was expressed on mmHg. |
| Total Insulin Secretion | Week 12 | The total insulin secretion was calculated by the insulinogenic index (ΔABC insulin / ΔABC glucose). |
| First Phase of Insulin Secretion | week 12 | The first phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0'). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index (BMI) | week 12 | The BMI was calculated by the square of the body height, and is universally expressed in units of kg/m2, resulting from mass in kilograms and height in metres. |
| Total Cholesterol (TC) | week 12 | The blood sample for determining of TC, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L. |
| Low-density Lipoprotein Cholesterol (LDL-C) | Week 12 | The blood sample for determining of LDL-C, was taken after an overnight fast and was calculated by Friedewald formula. The value was expressed on mmol/L. |
| Very-low Density Lipoprotein (VLDL) | week 12 | The blood sample for determining the VLDL, was taken after an overnight fast and was calculated as triglycerides/5. The value was expressed on mmol/L. |
| 2-hour Postload Plasma Glucose (2-h PG) | week 12 | The blood sample for determining of 2-h PG, was taken two hours after the ingestion of the drink with 75 g dextrose and was evaluated by spectrophotometry method. The value was expressed on mmol/L. |
| Area Under the Curve of Glucose (AUCG) | week 12 | The estimation for AUCG was calculated from parameters obtained during the 2 hours oral glucose tolerant test (OGTT) with 75 g dextrose by trapezoidal integration. The value was expressed mmol/L/min. |
| Area Under the Curve of Insulin (AUCI) | week 12 | The estimation for AUCI was calculated from parameters obtained during the 2 hours oral glucose tolerant test (OGTT) with 75 g dextrose by trapezoidal integration. The value was expressed on pmol/L/min. |
| Body Weight (BW) | week 12 | The BW was evaluated after an overnight fast, through a bioimpedance digital scale results are reported in kilograms with a decimal. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 600 mg dose per day. Two capsules of 300 mg, one in the morning with the first meal and the other at dinner during 90 days.
Placebo: Capsules of 300 mg two times per day before breakfast and dinner a total dose of 600 mg per day. During 90 days. | 12 |
| Gymnema Sylvestre 600 mg dose per day. Two capsules of 300 mg, one in the morning with the first meal and the other at dinner during 90 days.
Gymnema Sylvestre: Capsules of 300 mg of calcined magnesium two times per day before breakfast and dinner a total dose of 600 mg per day. During 90 days. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | Gymnema Sylvestre |
|---|---|---|---|
| 2-hour postload plasma glucose (2-h PG) | 7.67 mmol/L STANDARD_DEVIATION 184 | 7.72 mmol/L STANDARD_DEVIATION 1.78 | 7.61 mmol/L STANDARD_DEVIATION 1.89 |
| Age, Continuous | 42 years STANDARD_DEVIATION 4 | 41 years STANDARD_DEVIATION 4 | 43 years STANDARD_DEVIATION 1 |
| Area under the curve of glucose (AUCG) | 976 mmol/L/min STANDARD_DEVIATION 168 | 972 mmol/L/min STANDARD_DEVIATION 154 | 979 mmol/L/min STANDARD_DEVIATION 182 |
| Area under the curve of insulin (AUCI) | 62970 pmol/L/min STANDARD_DEVIATION 32307 | 64314 pmol/L/min STANDARD_DEVIATION 34914 | 61626 pmol/L/min STANDARD_DEVIATION 29700 |
| Body mass index (BMI) | 30.56 kg/m^2 STANDARD_DEVIATION 2.98 | 30.29 kg/m^2 STANDARD_DEVIATION 3.21 | 31.24 kg/m^2 STANDARD_DEVIATION 2.55 |
| Body weight (BW) | 80.2 kg STANDARD_DEVIATION 15.4 | 78.8 kg STANDARD_DEVIATION 16.1 | 81.3 kg STANDARD_DEVIATION 10.6 |
| Diastolic blood pressure (DBP) | 81 mmHg STANDARD_DEVIATION 6 | 81 mmHg STANDARD_DEVIATION 7 | 79 mmHg STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants | 12 Participants | 12 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 |
| Fasting plasma glucose (FPG) | 5.09 mmol/L STANDARD_DEVIATION 0.58 | 4.97 mmol/L STANDARD_DEVIATION 0.44 | 5.22 mmol/L STANDARD_DEVIATION 0.72 |
| First phase of insulin secretion | 1431 unitless STANDARD_DEVIATION 596 | 1403 unitless STANDARD_DEVIATION 682 | 1458 unitless STANDARD_DEVIATION 510 |
| high-density lipoprotein cholesterol (HDL-C) | 1.04 mmol/L STANDARD_DEVIATION 0.22 | 1.00 mmol/L STANDARD_DEVIATION 0.23 | 1.11 mmol/L STANDARD_DEVIATION 0.18 |
| Insulin sensitivity | 3.6 unitless STANDARD_DEVIATION 1.5 | 3.3 unitless STANDARD_DEVIATION 1.9 | 3.8 unitless STANDARD_DEVIATION 1.1 |
| Low-density lipoprotein cholesterol (LDL-C) | 2.15 mmol/L STANDARD_DEVIATION 0.52 | 2.12 mmol/L STANDARD_DEVIATION 0.59 | 2.48 mmol/L STANDARD_DEVIATION 0.93 |
| Region of Enrollment Mexico | 24 participants | 12 participants | 12 participants |
| Sex: Female, Male Female | 20 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 2 Participants |
| Systolic blood pressure (SBP) | 122 mmHg STANDARD_DEVIATION 15 | 123 mmHg STANDARD_DEVIATION 11 | 121 mmHg STANDARD_DEVIATION 10 |
| Total cholesterol (TC) | 4.59 mmol/L STANDARD_DEVIATION 0.63 | 4.53 mmol/L STANDARD_DEVIATION 0.52 | 4.60 mmol/L STANDARD_DEVIATION 1.06 |
| Total insulin secretion | 0.59 unitless STANDARD_DEVIATION 0.57 | 0.61 unitless STANDARD_DEVIATION 0.33 | 0.57 unitless STANDARD_DEVIATION 0.24 |
| Triglycerides (TGs) | 2.69 mmol/L STANDARD_DEVIATION 0.9 | 2.91 mmol/L STANDARD_DEVIATION 0.93 | 2.37 mmol/L STANDARD_DEVIATION 1.03 |
| Very-low density lipoprotein (VLDL) | 0.49 mmol/L STANDARD_DEVIATION 0.16 | 0.54 mmol/L STANDARD_DEVIATION 0.17 | 0.45 mmol/L STANDARD_DEVIATION 0.15 |
| Waist circumference (WC) | 98 cm STANDARD_DEVIATION 14 | 98 cm STANDARD_DEVIATION 14 | 99 cm STANDARD_DEVIATION 10 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 8 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Diastolic Blood Pressure (DBP)
The DBP was evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of DBP. The value was expressed on mmHg.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Diastolic Blood Pressure (DBP) | 83 mmHg | Standard Deviation 7 |
| Gymnema Sylvestre | Diastolic Blood Pressure (DBP) | 78 mmHg | Standard Deviation 8 |
p-value: 0.92Wilcoxon (Mann-Whitney)
Primary
Fasting Plasma Glucose (FPG)
The blood sample for determining of FPG, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Fasting Plasma Glucose (FPG) | 5.00 mmol/L | Standard Deviation 0.61 |
| Gymnema Sylvestre | Fasting Plasma Glucose (FPG) | 4.83 mmol/L | Standard Deviation 0.72 |
p-value: 0.08Wilcoxon (Mann-Whitney)
Primary
First Phase of Insulin Secretion
The first phase of insulin secretion was estimated using the Stumvoll index (1283+ 1.829 x insulin 30' - 138.7 x glucose 30' + 3.772 x insulin 0').
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | First Phase of Insulin Secretion | 1805 unitless | Standard Deviation 721 |
| Gymnema Sylvestre | First Phase of Insulin Secretion | 1366 unitless | Standard Deviation 472 |
p-value: 0.77Wilcoxon (Mann-Whitney)
Primary
High-density Lipoprotein Cholesterol (HDL-C)
The blood sample for determining of HDL-C, was taken after an overnight fast and was evaluated by colorimetric method. The value was expressed on mmol/L.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | High-density Lipoprotein Cholesterol (HDL-C) | 1.03 mmol/L | Standard Deviation 0.25 |
| Gymnema Sylvestre | High-density Lipoprotein Cholesterol (HDL-C) | 1.08 mmol/L | Standard Deviation 0.31 |
p-value: 0.79Wilcoxon (Mann-Whitney)
Primary
Insulin Sensitivity
The insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\].
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Insulin Sensitivity | 2.5 unitless | Standard Deviation 1.4 |
| Gymnema Sylvestre | Insulin Sensitivity | 4.1 unitless | Standard Deviation 2.1 |
p-value: 0.17Wilcoxon (Mann-Whitney)
Primary
Systolic Blood Pressure (SBP)
The SBP was evaluated with a digital sphygmomanometer with the subject sited down on a chair after a resting period of 5 minutes on three occasions. The mean of the three measures was considered as the value of SBP. The value was expressed on mmHg.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Systolic Blood Pressure (SBP) | 122 mmHg | Standard Deviation 13 |
| Gymnema Sylvestre | Systolic Blood Pressure (SBP) | 121 mmHg | Standard Deviation 11 |
p-value: 0.95Wilcoxon (Mann-Whitney)
Primary
Total Insulin Secretion
The total insulin secretion was calculated by the insulinogenic index (ΔABC insulin / ΔABC glucose).
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Insulin Secretion | 0.95 unitless | Standard Deviation 0.66 |
| Gymnema Sylvestre | Total Insulin Secretion | 0.59 unitless | Standard Deviation 0.25 |
p-value: 0.42Wilcoxon (Mann-Whitney)
Primary
Triglycerides (TGs)
The blood sample for determining of TGs, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Triglycerides (TGs) | 2.79 mmol/L | Standard Deviation 0.59 |
| Gymnema Sylvestre | Triglycerides (TGs) | 1.70 mmol/L | Standard Deviation 0.75 |
p-value: 0.07Wilcoxon (Mann-Whitney)
Primary
Waist Circumference (WC)
The WC was evaluated after an overnight fast with a flexible tape in the midpoint between the lowest rib and the iliac crest and is expressed in centimeters.
Time frame: Week 12
Population: All participants, including those who dropped out before the end were taken into account for statical analysis (intention to treat).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Waist Circumference (WC) | 101 cm | Standard Deviation 15 |
| Gymnema Sylvestre | Waist Circumference (WC) | 96 cm | Standard Deviation 7 |
p-value: 0.57Wilcoxon (Mann-Whitney)
Secondary
2-hour Postload Plasma Glucose (2-h PG)
The blood sample for determining of 2-h PG, was taken two hours after the ingestion of the drink with 75 g dextrose and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 2-hour Postload Plasma Glucose (2-h PG) | 6.83 mmol/L | Standard Deviation 2 |
| Gymnema Sylvestre | 2-hour Postload Plasma Glucose (2-h PG) | 7.22 mmol/L | Standard Deviation 3.05 |
p-value: 0.32Wilcoxon (Mann-Whitney)
Secondary
Area Under the Curve of Glucose (AUCG)
The estimation for AUCG was calculated from parameters obtained during the 2 hours oral glucose tolerant test (OGTT) with 75 g dextrose by trapezoidal integration. The value was expressed mmol/L/min.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve of Glucose (AUCG) | 965 mmol/L/min | Standard Deviation 235 |
| Gymnema Sylvestre | Area Under the Curve of Glucose (AUCG) | 914 mmol/L/min | Standard Deviation 267 |
p-value: 0.17Wilcoxon (Mann-Whitney)
Secondary
Area Under the Curve of Insulin (AUCI)
The estimation for AUCI was calculated from parameters obtained during the 2 hours oral glucose tolerant test (OGTT) with 75 g dextrose by trapezoidal integration. The value was expressed on pmol/L/min.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Curve of Insulin (AUCI) | 90816 pmol/L/min | Standard Deviation 45336 |
| Gymnema Sylvestre | Area Under the Curve of Insulin (AUCI) | 60468 pmol/L/min | Standard Deviation 37290 |
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Body Mass Index (BMI)
The BMI was calculated by the square of the body height, and is universally expressed in units of kg/m2, resulting from mass in kilograms and height in metres.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Body Mass Index (BMI) | 30.70 kg/m^2 | Standard Deviation 3.75 |
| Gymnema Sylvestre | Body Mass Index (BMI) | 30.43 kg/m^2 | Standard Deviation 2.23 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Body Weight (BW)
The BW was evaluated after an overnight fast, through a bioimpedance digital scale results are reported in kilograms with a decimal.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Body Weight (BW) | 80.3 kg | Standard Deviation 18.2 |
| Gymnema Sylvestre | Body Weight (BW) | 77.9 kg | Standard Deviation 8.4 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Low-density Lipoprotein Cholesterol (LDL-C)
The blood sample for determining of LDL-C, was taken after an overnight fast and was calculated by Friedewald formula. The value was expressed on mmol/L.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Low-density Lipoprotein Cholesterol (LDL-C) | 2.77 mmol/L | Standard Deviation 0.54 |
| Gymnema Sylvestre | Low-density Lipoprotein Cholesterol (LDL-C) | 2.69 mmol/L | Standard Deviation 0.59 |
p-value: 0.24Wilcoxon (Mann-Whitney)
Secondary
Total Cholesterol (TC)
The blood sample for determining of TC, was taken after an overnight fast and was evaluated by spectrophotometry method. The value was expressed on mmol/L.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Cholesterol (TC) | 5.04 mmol/L | Standard Deviation 0.62 |
| Gymnema Sylvestre | Total Cholesterol (TC) | 4.55 mmol/L | Standard Deviation 0.98 |
p-value: 0.83Wilcoxon (Mann-Whitney)
Secondary
Very-low Density Lipoprotein (VLDL)
The blood sample for determining the VLDL, was taken after an overnight fast and was calculated as triglycerides/5. The value was expressed on mmol/L.
Time frame: week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Very-low Density Lipoprotein (VLDL) | 0.56 mmol/L | Standard Deviation 0.12 |
| Gymnema Sylvestre | Very-low Density Lipoprotein (VLDL) | 0.35 mmol/L | Standard Deviation 0.15 |
p-value: 0.05Wilcoxon (Mann-Whitney)