Effect of Dihydromirycetin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Dihydromyricetin has demonstrated promising effects in glycemic control, insulin sensitivity and insulin secretion, that above mentioned findings show that dihydromyricetin has an excellent potential effect in the treatment of type 2 diabetes mellitus patients.

Detailed Description
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A double-blind, randomized clinical trial of three pharmacological groups in 36 patients with a diagnosis of type 2 diabetes mellitus in accordance with the American Diabetes Association (ADA) without treatment. They will be assigned randomly two groups of 12 patients, each one will receive dihydromyricetin 300 mg or metformin 850 mg, two times per day before having break-fast and before having dinner during 12 weeks. The Area Under the Curve of glucose and insulin will be calculated, total insulin secretion (Insulinogenic index), first-phase of insulin secretion (Stumvoll index) and insulin sensitivity (Matsuda index). This protocol is already approved by the local ethics committee and written informed consent it's going to be obtained from all volunteers. Statistical analysis will be presented through measures of central tendency and dispersion, average and deviation standard for quantitative variables; frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05.

Official Title
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Effect of Dihydromirycetin Administration on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dihydromyricetin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients both sexes Age between 30 and 60 years Diabetes mellitus type 2 of recent diagnosis without pharmacological treatment, with one of the following criteria (fasting blood glucose levels >126 mg/dL; postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose >200 mg/dl; or glycosylated hemoglobin between >6.5%) Informed consent signed Exclusion Criteria: Women with confirmed or suspected pregnancy, or under lactation and/or puerperium Previous treatment for glucose Fasting glucose ≥250 mg/dL Body Mass Index ≥34.9 kg/m2 Known uncontrolled renal, hepatic, heart or thyroid diseased Hypersensibility to ingredients of intervention Triglycerides ≥500 mg/dL Total cholesterol ≥240 mg/dL Blood Pressure ≥140/90 mmHg

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
Interventional Model Description: Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dihydromyricetin<br>Dihydromyricetin capsules, 300 mg, two times per day before break-fast and dinner during 12 weeks. | Drug: Dihydromyricetin<br>* The intervention wiil be 300 mg, two times per day before break-fast and dinner during 12 weeks.<br>* Other names: Ampelopsis grossedentata Extract;|
| Experimental: Metformin<br>Metformin capsules, 850 mg, two times per day before break-fast and dinner during 12 weeks. | Drug: Metformin<br>* The intervention wiil be 850 mg, two times per day before break-fast and dinner during 12 weeks.<br>* Other names: Brad Predial;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting glucose | Changes in fasting glucose levels after 12 weeks of intervention with dihydromyricetin and metformin. The fasting glucose levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12. | Baseline to Week 12 | 
| Postprandial glucose | Changes in postprandial glucose levels after 12 weeks of intervention with dihydromyricetin and metformin. Postprandial glucose will be evaluated at baseline and week 12 after a oral glucose tolerance test with enzymatic/colorimetric techniques and the entered values reflect the insulin sensitivity at week 12. | Baseline to Week 12 | 
| Glycosylated hemoglobin | Changes in glycosylated hemoglobin (A1C) after 12 weeks of intervention with dihydromyricetin and metformin. Glycosylated hemoglobin will be evaluated at baseline and week 12 by high pressure liquid chromatography (HPLC) and the entered values reflect the glycosylated hemoglobin at week 12. | Baseline to Week 12 | 
| Insulin sensitivity | Insulin sensitivity will be calculated at baseline and week 12 with Matsuda index and the entered values reflect the insulin sensitivity at week 12. | Baseline to Week 12 | 
| Total insulin secretion | Total insulin secretion will be calculated at baseline and week 12 with insulinogenic index and the entered values reflect the total insulin secretion at week 12. | Baseline to Week 12 | 
| First phase of insulin secretion | The first phase of insulin secretion will be calculated at baseline and week 12 with Stumvoll index and the entered values reflect the first phase of insulin secretion at week 12. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist Circumference | Waist circumference will be evaluated at baseline and at week 12 with a flexible tape. | Baseline to Week 12 | 
| Body Weigh | The body weight will be measured at baseline, week 4, week 8 and week 12 with a bioimpedance balance and the entered values reflect the body weight at week 12. | Baseline, week 4, week 8 and week 12 | 
| Body Mass Index | Body Mas Index will be calculated at baseline, week 4, week 8 and week 12 with the Quetelet index formula and the entered values reflect the body mass index at week 12. | Baseline, week 4, week 8 and week 12 | 
| C reactive protein | C reactive protein will be evaluated at baseline and week 12 by enzyme-linked immunosorbent assay (ELISA) and the entered values reflect the creatinine levels at week 12 | Baseline to Week 12 | 
| Interleukin 6 | Interleukin 6 will be evaluated at the beginning and during week 12 using the enzyme-linked immunosorbent assay (ELISA) and the values entered reflect creatinine levels at week 12 | Baseline to Week 12 | 
| Total Cholesterol | Total cholesterol levels will be evaluated at baseline and week 12 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 12 | Baseline to Week 12 | 
| Triglycerides levels | Triglycerides levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 12 | Baseline to Week 12 | 
| High Density Lipoprotein (c-HDL) levels | c-HDL levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12 | Basline to Week 12 | 
| Low Density Lipoproteins (c-LDL) levels | c-LDL levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-LDL level at week 12 | Baseline to Week 12 | 
| Creatinine levels | Creatinine levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques | Baseline to Week 12 | 
| Alanine aminotransferase (ALT) levels | ALT levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques | Baseline to Week 12 | 
| Aspartate aminotransferase (AST) levels | AST levels will be evaluated at baseline and week 12 with enzymatic/colorimetric techniques | Baseline to Week 12 | 
| Blood pressure | Blood pressure will be measured at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the blood pressure at week 12 | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dihydromyricetin, metformin, type 2 diabetes mellitus