Effect of Propolis or Metformin Administration on Glycemic Control in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The aim of this study was to evaluate the effect of propolis or metformin on glycemic control in patients with type 2 diabetes mellitus without pharmacological treatment. All patients received for 12 weeks propolis, metformin or placebo. Fasting serum glucose, 2-h serum glucose after oral glucose tolerance test, glycated hemoglobin A1c, a metabolic profile, areas under the curve of glucose and insulin, insulinogenic index, Stumvoll index, and Matsuda index were measured.

Detailed Description
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A randomized, double-blind, placebo-controlled clinical trial of three pharmacological groups was carried out, with the participation of 36 patients with type 2 Diabetes Mellitus without pharmacological treatment. At the beginning and end of the study, fasting serum glucose, 2-h serum glucose after oral glucose tolerance test, glycated hemoglobin A1c, and a metabolic profile were measured. Areas under the curve of glucose and insulin, total insulin secretion insulinogenic index), the first phase of insulin secretion (Stumvoll index), and insulin sensitivity (Matsuda index) were calculated. All patients received for 12 weeks two capsules a day, one before the first bite of breakfast and another before the first bite of dinner. 12 of them took propolis (300 mg), another 12 received metformin (850 mg), and 12 more placebo in the same pharmacological presentation. 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-group differences were evaluated using Kruskal-Wallis and Mann-Whitney U-tests, while inter-group differences were calculated with the Wilcoxon test; p≤0.05 was considered significant.

Official Title
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Effect of Propolis or Metformin Administration on Glycemic Control in Patients With Type 2 Diabetes Mellitus Without Pharmacological Treatment

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Propolis
* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients both sexes Age between 30 and 60 years Mild to moderate physical activity Stable body weight for at least 12 weeks prior to the study BMI 25.0 - 34.9 kg/m2 Diabetes mellitus type 2 of recent diagnosis without pharmacological treatment, with one of the following criteria (fasting blood glucose levels >126 mg/dl; or postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose >200 mg/dl Informed consent signed Exclusion Criteria: Women with confirmed or suspected pregnancy Women under lactation and/or puerperium Previous treatment for glucose Fasting glucose ≥250 mg/dL Known uncontrolled renal, hepatic, heart or thyroid diseased Hypersensibility to ingredients of intervention Known allergies to bee stings or their derived products Triglycerides ≥500 mg/dL Total cholesterol ≥240 mg/dL

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propolis<br>Propolis capsules, 300 mg, two times per day before break-fast and dinner during 12 weeks. | Drug: Propolis<br>* Propolis capsules, 300 mg, two times per day before break-fast and dinner during 12 weeks.<br>|
| Experimental: Metformin<br>Metformin capsules, 850 mg, two times per day before break-fast and dinner during 12 weeks. | Drug: Metformin<br>* Metformin capsules, 850 mg, two times per day before break-fast and dinner during 12 weeks.<br>* Other names: Metformin hydrochloride;|
| Placebo Comparator: Placebo<br>Placebo capsules, two times per day before break-fast and dinner during 12 weeks. | Drug: Placebo<br>* Calcined magnesium, two times per day before break-fast and dinner during 12 weeks.<br>* Other names: Calcined magnesium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Serum Glucose | The fasting glucose levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12 | Week 12 | 
| 2 Hours After Oral Glucose Tolerance Test in Week 12 | 2-h serum glucose levels were evaluated at week 12 after a oral glucose tolerance test with enzymatic/colorimetric techniques and the entered values reflect the insulin sensitivity at week 12 | Week 12 | 
| Glycosylated Hemoglobin (A1C) | Glycosylated hemoglobin was evaluated at week 12 by high pressure liquid chromatography (HPLC) and the entered values reflect the glycosylated hemoglobin at week 12 | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Insulin Secretion | Total insulin secretion was calculated at week 12 with insulinogenic index and the entered values reflect the total insulin secretion at week 12. The insulinogenic index is a ratio that relates enhancement of circulating insulin to the magnitude of the corresponding glycemic stimulus. Total insulin secretion was calculated with the insulinogenic index (ΔAUC insulin/ΔAUC glucose), the entered values reflect the total insulin secretion | Week 12 | 
| Insulin Sensitivity | Insulin sensitivity was calculated at week 12 with Matsuda index and the entered values reflect the insulin sensitivity at week 12. Matsuda Index value is used to indicate insulin resistance on diabetes. 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)]. The entered values reflect the insulin sensitivity | Week 12 | 
| First Phase of Insulin Secretion | The first phase of insulin secretion was calculated at week 12 with Stumvoll index and the entered values reflect the frst phase of insulin secretion at week 12. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. 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'), the entered values reflect the first phase of insulin secretion | Week 12 | 
| AUC Glucose | Area under the curve (AUC) of glucose was calculated with the polygonal formula. The area under the curve (AUC) of glucose, (0.5 * glucose (G) 0´ + (G 30´+G 60´ + G 90´) + 0.5 * G 120´) * 30; has been widely used for calculating the glycemic index and for evaluating the efficacy of medications for postprandial hyperglycemia. | Week 12 | 
| AUC Insulin | Area under the curve (AUC) of insulin was calculated with the polygonal formula. The area under the curve (AUC) of insulin, (0.5 * Insulin (I) 0´ + (I 30´+I 60´ + I 90´) + 0.5 * I 120´) * 30; has been widely used for calculating the glycemic index and for evaluating the efficacy of medications for postprandial hyperinsulinemia. | Week 12 | 
| Glucose 30 Min After Oral Glucose Tolerance Test at 12 Week | The glucose levels 30' were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the glucose 30' at week 12 | Week 12 | 
| Glucose 60 Min After Oral Glucose Tolerance Test at 12 Week | The glucose levels 60' were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the glucose 60' at week 12 | Week 12 | 
| Glucose 90 Min After Oral Glucose Tolerance Test at 12 Week | The glucose levels 90' were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the glucose 90' at week 12. | Week 12 | 
| Waist Circumference | Waist circumference was evaluated at week 12 with a flexible tape | Week 12 | 
| Body Weight | The body weight was measured at week 12 with a bioimpedance balance and the entered values reflect the body weight at week 12 | Week 12 | 
| Body Mass Index | Body Mas Index was calculated at week 12 with the Quetelet index formula and the entered values reflect the body mass index at week 12 | Week 12 | 
| Percentage of Fat Mass | Percentage of fat mass was evaluated through bioimpedance. | Week 12 | 
| Total Cholesterol | Total cholesterol levels were evaluated at week 12 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12 | Week 12 | 
| Triglycerides | Triglycerides levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12 | Week 12 | 
| High Density Lipoprotein Cholesterol (c-HDL) | c-HDL levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12 | Week 12 | 
| Low Density Lipoproteins Cholesterol (c-LDL) | c-LDL levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-LDL level at week 12 | Week 12 | 
| Very Low Density Lipoprotein (c-VLDL) | Very low density lipoprotein (c-VLDL) was analyzed with the cholesterol oxidase/peroxidase technique by enzymatic colorimetric methods on an automatic analyzer. | Week 12 | 
| Creatinine | Creatinine levels were evaluated at week 12 with enzymatic/colorimetric techniques | Week 12 | 
| Uric Acid | Uric acid levels were evaluated at week 12 with enzymatic/colorimetric techniques | Week 12 | 
| Systolic Blood Pressure | The systolic blood pressure was evaluated at week 12 with a digital sphygmomanometer and the entered values reflect the systolic blood pressure at week 12. | Week 12 | 
| Diastolic Blood Pressure | The diastolic blood pressure was evaluated at week 12 with a digital sphygmomanometer and the entered values reflect the diastolic blood pressure at week 12. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus type 2, Glycemic control, Propolis, Metformin, Pharmacological treatment-naïve patients