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

Phase 2

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Placebo
Drug: Metformin
Drug: Propolis

Registration Number: NCT03416127

Lead Sponsor: University of Guadalajara

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo capsules, two times per day before break-fast and dinner during 12 weeks.
Metformin	Metformin	Metformin capsules, 850 mg, two times per day before break-fast and dinner during 12 weeks.
Propolis	Propolis	Propolis capsules, 300 mg, two times per day before break-fast and dinner during 12 weeks.

Primary Outcome Measures

Name	Time	Method
Fasting Serum Glucose	Week 12	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
Glycosylated Hemoglobin (A1C)	Week 12	Glycosylated hemoglobin was evaluated at week 12 by high pressure liquid chromatography (HPLC) and the entered values reflect the glycosylated hemoglobin at week 12
2 Hours After Oral Glucose Tolerance Test in Week 12	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

Secondary Outcome Measures

Name	Time	Method
Glucose 90 Min After Oral Glucose Tolerance Test at 12 Week	Week 12	The glucose levels 90' were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the glucose 90' at week 12.
Waist Circumference	Week 12	Waist circumference was evaluated at week 12 with a flexible tape
Body Mass Index	Week 12	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
Percentage of Fat Mass	Week 12	Percentage of fat mass was evaluated through bioimpedance.
Total Cholesterol	Week 12	Total cholesterol levels were evaluated at week 12 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12
Triglycerides	Week 12	Triglycerides levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12
High Density Lipoprotein Cholesterol (c-HDL)	Week 12	c-HDL levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12
Low Density Lipoproteins Cholesterol (c-LDL)	Week 12	c-LDL levels were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-LDL level at week 12
Very Low Density Lipoprotein (c-VLDL)	Week 12	Very low density lipoprotein (c-VLDL) was analyzed with the cholesterol oxidase/peroxidase technique by enzymatic colorimetric methods on an automatic analyzer.
Creatinine	Week 12	Creatinine levels were evaluated at week 12 with enzymatic/colorimetric techniques
Insulin Sensitivity	Week 12	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
First Phase of Insulin Secretion	Week 12	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
AUC Glucose	Week 12	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.
Total Insulin Secretion	Week 12	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
Glucose 30 Min After Oral Glucose Tolerance Test at 12 Week	Week 12	The glucose levels 30' were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the glucose 30' at week 12
Body Weight	Week 12	The body weight was measured at week 12 with a bioimpedance balance and the entered values reflect the body weight at week 12
AUC Insulin	Week 12	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.
Glucose 60 Min After Oral Glucose Tolerance Test at 12 Week	Week 12	The glucose levels 60' were evaluated at week 12 with enzymatic/colorimetric techniques and the entered values reflect the glucose 60' at week 12
Uric Acid	Week 12	Uric acid levels were evaluated at week 12 with enzymatic/colorimetric techniques
Systolic Blood Pressure	Week 12	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.
Diastolic Blood Pressure	Week 12	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.

Trial Locations

Locations (1): Intstituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara
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Guadalajara, Jalisco, Mexico