Impaired Glucose Tolerance
Conditions
Keywords
Gymnema Sylvestre, Glycemic control
Brief summary
Prediabetes (PD) was defined as an state in which glucose levels are above normal but not enough to meet criteria for the diagnosis of type 2 diabetes (T2D). PD can be presented as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and glycated hemoglobin A1c (A1C) altered. The International Diabetes Federation (IDF) reported that in 2013 the prevalence of IGT was 6.9% which is equivalent to approximately 316 million individuals with IGT, it is expected that by 2035 this number will increase to 417 million people affected. Many hypoglycemic effects attributed to Gymnema sylvestre have been reported, including: increase of insulin secretion, regeneration of pancreatic islet cells, increased glucose utilization in various ways and inhibition of glucose uptake in the intestine.
Detailed description
The target is to evaluate the effect of the administration of Gymnema Sylvestre on glycemic control, insulin secretion and insulin sensibility on patients with IGT. The investigators will conduct a double-blind trial, randomized, placebo control group, each group 12 female and male patients, between 30 and 59 years old with IGT (2-h values in the oral glucose tolerance test, OGTT) from 140 mg / dL to 199 mg / dL), Body Mass Index (BMI) from 25 to 34.9 kg / m2. Randomization will determine who will receive the intervention during the 9-week trial (Gymnema Sylvestre capsules, 300 mg 2 times daily with the first bite of breakfast and dinner or homologated placebo capsules). The clinical findings and laboratory tests include a metabolic profile and biosafety, which will be made at baseline and at week 9. Body weight, body fat, BMI and blood pressure will be determined during the initial and final visit. Adverse events and adherence to treatment will be documented. Statistical analysis: Mann-Whitney U test, Wilcoxon and Fisher exact test. It is considered with significance at p \<0.05.
Interventions
Gymnema Sylvestre, 300mg capsules 2 times daily with the first bite of breakfast and dinner
DRUGPlacebo
Placebo, 300mg capsules 2 times daily with the first bite of breakfast and dinner
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 59 Years
Healthy volunteers
No
Inclusion criteria
* BMI: 25.0-34.99 kg / m2. * Diagnosis of IGT (2h-OGTT Values between 140mg / dl and 199mg / dl.) * Written informed consent. * body weight stable over the last 3 months. * Women in follicular phase of the menstrual cycle (days 3 to 8 of the cycle) at the time of laboratory tests. * Women who are not contemplated get pregnant within the next 6 months.
Exclusion criteria
* Women pregnant or breastfeeding. * Physical or mental disability that makes it impossible to perform the intervention. * Diagnosis of hypertension or heart failure. * Smokers. * Untreated thyroid disease. * Consumption of oral agents or other medications or supplements with proven properties that modify the behavior of glucose and lipids (oral hypoglycemic agents, insulin, lipid-lowering). * Diagnosis of liver disease or elevation twice of the upper normal value of liver enzymes. * Diagnosis of renal disease or creatinine \> 1.5 mg / dl. * Diagnosis of Type 2 Diabetes Mellitus (T2DM) Fasting glucose ≥ 126 mg / dL and/or 2h-OGTT ≥ 200 mg / dL and/or A1C ≥ 6.5%. * Total Cholesterol ≥ 280 mg/dL. * Triglycerides ≥ 300 mg/dL. * Known allergy to calcined magnesia or Gymnema sylvestre.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose | 90 days | After intervention by spectrophotometry |
| 2-hour Post Load Plasma Glucose (2-h PG) | 90 days | 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. |
| Glycated Hemoglobin A1c (A1C) | 90 days | After intervention by high-performance liquid chromatography |
| Total Insulin Secretion (Insulinogenic Index) | 90 days | Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin / ΔABC glucose) after intervention. |
| First Phase of Insulin Secretion | 90 days | 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') after intervention. |
| Insulin Sensitivity (Matsuda Index) | 90 days | Insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\] after intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diastolic Blood Pressure (DBP) | 12 weeks | The Diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 |
| Total Cholesterol | 90 days | After intervention by spectrophotometry |
| Triglycerides | 90 days | After intervention by spectrophotometry |
| Area Under the Curve of Glucose | 90 days | Area under the curve of glucose was obtained using the trapezoidal integration. |
| Low Density Lipoprotein | 90 days | After intervention by spectrophotometry |
| Very Low Density Lipoprotein | 90 days | After intervention by spectrophotometry |
| Creatinine | 90 days | After intervention by spectrophotometry |
| High Density Lipoprotein Cholesterol | 90 days | After intervention by spectrophotometry |
| Area Under the Curve of Insulin | 90 days | After intervention area under the curve of insulin |
| Body Weight (BW) | 12 weeks | 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 |
| Body Mass Index (BMI) | 12 weeks | 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 |
| Waist Circumference (WC) | 12 weeks | Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflects the waist circumference measure at week 12 |
| Systolic Blood Pressure (SBP) | 12 weeks | The Systolic Blood Pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gymnema Sylvestre Patients with IGT
Gymnema Sylvestre: Gymnema Sylvestre, 300mg capsules 2 times daily with the first bite of breakfast and dinner | 15 |
| Placebo Patients with IGT
Placebo: Placebo, 300mg capsules 2 times daily with the first bite of breakfast and dinner | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Gymnema Sylvestre |
|---|---|---|---|
| 2-hour postload plasma glucose (2-h PG) | 8.6 mmol/L STANDARD_DEVIATION 0.8 | 8.9 mmol/L STANDARD_DEVIATION 1 | 9.1 mmol/L STANDARD_DEVIATION 1.2 |
| Age, Continuous | 44 Years STANDARD_DEVIATION 7 | 45 Years STANDARD_DEVIATION 9 | 47 Years STANDARD_DEVIATION 10 |
| Area under the curve of glucose (AUCG) | 1078 mmol/L/min STANDARD_DEVIATION 137 | 1120 mmol/L/min STANDARD_DEVIATION 146 | 1157 mmol/L/min STANDARD_DEVIATION 147 |
| Area under the curve of insulin (AUCI) | 63,544 pmol/L/min | 65946 pmol/L/min STANDARD_DEVIATION 24188 | 68,348 pmol/L/min |
| Body Mass Index (BMI) | 29.8 kg/m^2 STANDARD_DEVIATION 5.2 | 30.4 kg/m^2 STANDARD_DEVIATION 4.4 | 31.1 kg/m^2 STANDARD_DEVIATION 3.7 |
| Body Weight (BW) | 79.1 kg STANDARD_DEVIATION 16.8 | 79.3 kg STANDARD_DEVIATION 14.3 | 79.6 kg STANDARD_DEVIATION 11.9 |
| Creatinine | 70.8 µmol/L STANDARD_DEVIATION 26.5 | 70.8 µmol/L STANDARD_DEVIATION 17.7 | 79.5 µmol/L STANDARD_DEVIATION 17.7 |
| Diastolic blood pressure (DBP) | 77 mmHg STANDARD_DEVIATION 8 | 77 mmHg STANDARD_DEVIATION 11 | 77 mmHg STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 30 Participants | 15 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) | 5.6 mmol/L STANDARD_DEVIATION 0.4 | 5.8 mmol/L STANDARD_DEVIATION 0.4 | 5.9 mmol/L STANDARD_DEVIATION 0.4 |
| First phase of insulin secretion | 1391 unitless STANDARD_DEVIATION 712 | 1344 unitless STANDARD_DEVIATION 627 | 1297 unitless STANDARD_DEVIATION 550 |
| Glycated hemoglobin A1c | 5.6 Percent of glycated hemoglobin STANDARD_DEVIATION 0.2 | 5.7 Percent of glycated hemoglobin STANDARD_DEVIATION 0.3 | 5.8 Percent of glycated hemoglobin STANDARD_DEVIATION 0.3 |
| high-density lipoprotein cholesterol (HDL-C) | 0.9 mmol/L STANDARD_DEVIATION 0.3 | 0.9 mmol/L STANDARD_DEVIATION 0.2 | 1.0 mmol/L STANDARD_DEVIATION 0.1 |
| Insulin sensitivity | 2.5 unitless STANDARD_DEVIATION 1.5 | 2.1 unitless STANDARD_DEVIATION 1.2 | 1.8 unitless STANDARD_DEVIATION 0.8 |
| Low-density lipoprotein cholesterol (LDL-C) | 3.5 mmol/L STANDARD_DEVIATION 0.5 | 3.5 mmol/L STANDARD_DEVIATION 0.7 | 3.5 mmol/L STANDARD_DEVIATION 0.8 |
| Region of Enrollment Mexico | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 11 Participants | 22 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 Participants |
| Systolic blood pressure (SBP) | 119 mmHg STANDARD_DEVIATION 12 | 118 mmHg STANDARD_DEVIATION 12 | 117 mmHg STANDARD_DEVIATION 12 |
| Total cholesterol (TC) | 5.2 mmol/L STANDARD_DEVIATION 0.9 | 5.1 mmol/L STANDARD_DEVIATION 0.9 | 5.1 mmol/L STANDARD_DEVIATION 0.1 |
| Total insulin secretion | 0.54 unitless STANDARD_DEVIATION 0.22 | 0.54 unitless STANDARD_DEVIATION 0.22 | 0.56 unitless STANDARD_DEVIATION 0.2 |
| Triglycerides (TGs) | 1.5 mmol/L STANDARD_DEVIATION 0.7 | 1.7 mmol/L STANDARD_DEVIATION 1 | 1.8 mmol/L STANDARD_DEVIATION 1.3 |
| Very-low density lipoprotein (VLDL) | 0.3 mmol/L STANDARD_DEVIATION 0.1 | 0.3 mmol/L STANDARD_DEVIATION 0.2 | 0.4 mmol/L STANDARD_DEVIATION 0.3 |
| Waist circumference (WC) | 98.8 cm STANDARD_DEVIATION 9.8 | 98 cm STANDARD_DEVIATION 8.3 | 97.3 cm STANDARD_DEVIATION 6.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 4 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
2-hour Post Load 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: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | 2-hour Post Load Plasma Glucose (2-h PG) | 7.8 mmol/L | Standard Deviation 1.7 |
| Placebo | 2-hour Post Load Plasma Glucose (2-h PG) | 7.9 mmol/L | Standard Deviation 1.1 |
Primary
Fasting Plasma Glucose
After intervention by spectrophotometry
Time frame: 90 days
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 |
|---|---|---|---|
| Gymnema Sylvestre | Fasting Plasma Glucose | 77.4 mmol/L | Standard Deviation 11.6 |
| Placebo | Fasting Plasma Glucose | 77.7 mmol/L | Standard Deviation 13.2 |
Primary
First Phase of Insulin Secretion
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') after intervention.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | First Phase of Insulin Secretion | 1399 Unitless | Standard Deviation 552 |
| Placebo | First Phase of Insulin Secretion | 1528 Unitless | Standard Deviation 677 |
Primary
Glycated Hemoglobin A1c (A1C)
After intervention by high-performance liquid chromatography
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Glycated Hemoglobin A1c (A1C) | 5.4 Percent of glycated hemoglobin | Standard Deviation 0.4 |
| Placebo | Glycated Hemoglobin A1c (A1C) | 5.7 Percent of glycated hemoglobin | Standard Deviation 0.5 |
Primary
Insulin Sensitivity (Matsuda Index)
Insulin sensitivity was calculated with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\] after intervention.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Insulin Sensitivity (Matsuda Index) | 2.4 Unitless | Standard Deviation 1.2 |
| Placebo | Insulin Sensitivity (Matsuda Index) | 2.5 Unitless | Standard Deviation 1.2 |
Primary
Total Insulin Secretion (Insulinogenic Index)
Total insulin secretion was calculated with the insulinogenic index (ΔABC insulin / ΔABC glucose) after intervention.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Total Insulin Secretion (Insulinogenic Index) | 0.51 Unitless | Standard Deviation 0.21 |
| Placebo | Total Insulin Secretion (Insulinogenic Index) | 0.49 Unitless | Standard Deviation 0.18 |
Secondary
Area Under the Curve of Glucose
Area under the curve of glucose was obtained using the trapezoidal integration.
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Area Under the Curve of Glucose | 1075 mmol/l/min | Standard Deviation 253 |
| Placebo | Area Under the Curve of Glucose | 1018 mmol/l/min | Standard Deviation 158 |
Secondary
Area Under the Curve of Insulin
After intervention area under the curve of insulin
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Area Under the Curve of Insulin | 56968 mmol/l/min | Standard Deviation 20787 |
| Placebo | Area Under the Curve of Insulin | 53374 mmol/l/min | Standard Deviation 20663 |
Secondary
Body Mass Index (BMI)
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: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Body Mass Index (BMI) | 30.3 kg/m^2 | Standard Deviation 3.6 |
| Placebo | Body Mass Index (BMI) | 29.3 kg/m^2 | Standard Deviation 4.4 |
Secondary
Body Weight (BW)
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: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Body Weight (BW) | 77.4 kg | Standard Deviation 11.6 |
| Placebo | Body Weight (BW) | 77.7 kg | Standard Deviation 13.2 |
Secondary
Creatinine
After intervention by spectrophotometry
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Creatinine | 70.8 µmol/L | Standard Deviation 17.6 |
| Placebo | Creatinine | 70.8 µmol/L | Standard Deviation 17.6 |
Secondary
Diastolic Blood Pressure (DBP)
The Diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Diastolic Blood Pressure (DBP) | 75 mmHg | Standard Deviation 10 |
| Placebo | Diastolic Blood Pressure (DBP) | 77 mmHg | Standard Deviation 8 |
Secondary
High Density Lipoprotein Cholesterol
After intervention by spectrophotometry
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | High Density Lipoprotein Cholesterol | 0.9 mmol/L | Standard Deviation 0.2 |
| Placebo | High Density Lipoprotein Cholesterol | 1.0 mmol/L | Standard Deviation 0.3 |
Secondary
Low Density Lipoprotein
After intervention by spectrophotometry
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Low Density Lipoprotein | 2.5 mmol/L | Standard Deviation 1.3 |
| Placebo | Low Density Lipoprotein | 3.2 mmol/L | Standard Deviation 1.6 |
Secondary
Systolic Blood Pressure (SBP)
The Systolic Blood Pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Systolic Blood Pressure (SBP) | 120 mmHg | Standard Deviation 15 |
| Placebo | Systolic Blood Pressure (SBP) | 120 mmHg | Standard Deviation 14 |
Secondary
Total Cholesterol
After intervention by spectrophotometry
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Total Cholesterol | 4.7 mmol/L | Standard Deviation 1.2 |
| Placebo | Total Cholesterol | 5.4 mmol/L | Standard Deviation 1 |
Secondary
Triglycerides
After intervention by spectrophotometry
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Triglycerides | 1.7 mmol/L | Standard Deviation 0.9 |
| Placebo | Triglycerides | 1.6 mmol/L | Standard Deviation 0.7 |
Secondary
Very Low Density Lipoprotein
After intervention by spectrophotometry
Time frame: 90 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Very Low Density Lipoprotein | 0.3 mmol/L | Standard Deviation 0.2 |
| Placebo | Very Low Density Lipoprotein | 0.3 mmol/L | Standard Deviation 0.1 |
Secondary
Waist Circumference (WC)
Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflects the waist circumference measure at week 12
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gymnema Sylvestre | Waist Circumference (WC) | 97.3 cm | Standard Deviation 7.7 |
| Placebo | Waist Circumference (WC) | 99 cm | Standard Deviation 7.6 |