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Type 2 diabetes mellitus is associated with endothelial dysfunction, which contributes to increased cardiovascular risk. Chronic hyperglycemia induces oxidative stress and reduces nitric oxide bioavailability, leading to impaired endothelial function. Resveratrol, a natural polyphenol with antioxidant and anti-inflammatory properties, has been shown to improve endothelial function in experimental studies.
This randomized controlled trial aims to evaluate the effectiveness of resveratrol supplementation in improving endothelial dysfunction and metabolic control in patients with type 2 diabetes mellitus. Endothelial function will be assessed using flow-mediated dilatation (FMD) of the brachial artery and serum endothelial nitric oxide synthase (eNOS) levels. Metabolic parameters including fasting blood glucose, postprandial glucose, HbA1c, and lipid profile will also be evaluated.
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease, in which endothelial dysfunction plays a central role. Chronic hyperglycemia leads to oxidative stress and increased production of reactive oxygen species, resulting in decreased nitric oxide bioavailability and impaired endothelial function.
Resveratrol (3,5,4-trihydroxystilbene) is a natural polyphenol with antioxidant, anti-inflammatory, and endothelial-protective effects. Previous experimental and clinical studies have suggested that resveratrol may improve endothelial function through enhancement of endothelial nitric oxide synthase (eNOS) activity and reduction of oxidative stress.
This study is a randomized controlled trial involving patients with type 2 diabetes mellitus and endothelial dysfunction. Participants will be randomized to receive either resveratrol 50 mg or placebo for 12 weeks. Endothelial function will be evaluated using flow-mediated dilatation (FMD) of the brachial artery and serum eNOS levels before and after intervention.
Metabolic control will be assessed by measuring fasting blood glucose, postprandial glucose, HbA1c, and lipid profile including LDL, HDL, and triglycerides. The primary objective is to determine whether resveratrol supplementation improves endothelial function, while secondary outcomes include changes in metabolic parameters and safety evaluation.
This study aims to provide evidence regarding the role of resveratrol as an adjunct therapy in improving endothelial function and metabolic control in patients with type 2 diabetes mellitus.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Resveratrol Group | Experimental | Participants receive resveratrol 50 mg orally once daily for 12 weeks in addition to standard therapy for type 2 diabetes mellitus. |
|
| Placebo Group | Placebo Comparator | Participants receive placebo orally once daily for 12 weeks in addition to standard therapy for type 2 diabetes mellitus. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resveratrol | Drug | Resveratrol 50 mg administered orally once daily for 12 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Flow-Mediated Dilatation (FMD) of the Brachial Artery | Flow-mediated dilatation (FMD) will be measured as the percentage change in brachial artery diameter using ultrasound before and after intervention. | Baseline and 12 weeks |
| Change in Serum Endothelial Nitric Oxide Synthase (eNOS) Levels | Serum endothelial nitric oxide synthase (eNOS) levels will be measured to assess endothelial function before and after intervention. | Baseline and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fasting Blood Glucose | Fasting blood glucose levels will be measured to assess glycemic control before and after intervention. | Baseline and 12 weeks |
| Change in Postprandial Blood Glucose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yulianto Kusnadi, MD, DR | Faculty of Medicine Universitas Sriwijaya / RSUP Dr. Mohammad Hoesin Palembang | Principal Investigator |
| Rita Sriwulandari, MD | Division of Endocrinology, FK UNSRI / RSMH Palembang | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitas Sriwijaya | Palembang | South Sumatera | 30126 | Indonesia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37525273 | Result | Marassi M, Fadini GP. The cardio-renal-metabolic connection: a review of the evidence. Cardiovasc Diabetol. 2023 Jul 31;22(1):195. doi: 10.1186/s12933-023-01937-x. | |
| 32150686 | Result | Triggle CR, Ding H, Marei I, Anderson TJ, Hollenberg MD. Why the endothelium? The endothelium as a target to reduce diabetes-associated vascular disease. Can J Physiol Pharmacol. 2020 Jul;98(7):415-430. doi: 10.1139/cjpp-2019-0677. Epub 2020 Mar 9. |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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Participants with type 2 diabetes mellitus and endothelial dysfunction will be randomized into two parallel groups to receive either resveratrol 50 mg or placebo for 12 weeks.
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Participants, care providers, investigators, and outcome assessors will be blinded to group allocation. Resveratrol and placebo will be identical in appearance and packaging.
| Placebo | Drug | Matching placebo administered orally once daily for 12 weeks. |
|
Postprandial blood glucose levels will be measured to assess glycemic control before and after intervention.
| Baseline and 12 weeks |
| Change in Hemoglobin A1c (HbA1c) | HbA1c levels will be measured to evaluate long-term glycemic control before and after intervention. | Baseline and 12 weeks |
| Change in LDL Cholesterol | LDL cholesterol levels will be measured before and after intervention. | Baseline and 12 weeks |
| Change in HDL Cholesterol | HDL cholesterol levels will be measured before and after intervention. | Baseline and 12 weeks |
| Change in Triglyceride Levels | Triglyceride levels will be measured before and after intervention. | Baseline and 12 weeks |
| 30856465 | Result | Li J, Zhong Z, Yuan J, Chen X, Huang Z, Wu Z. Resveratrol improves endothelial dysfunction and attenuates atherogenesis in apolipoprotein E-deficient mice. J Nutr Biochem. 2019 May;67:63-71. doi: 10.1016/j.jnutbio.2019.01.022. Epub 2019 Feb 10. |
| 32058210 | Result | Huang DD, Shi G, Jiang Y, Yao C, Zhu C. A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications. Biomed Pharmacother. 2020 May;125:109767. doi: 10.1016/j.biopha.2019.109767. Epub 2020 Feb 12. |
| 30621358 | Result | Fourny N, Lan C, Seree E, Bernard M, Desrois M. Protective Effect of Resveratrol against Ischemia-Reperfusion Injury via Enhanced High Energy Compounds and eNOS-SIRT1 Expression in Type 2 Diabetic Female Rat Heart. Nutrients. 2019 Jan 6;11(1):105. doi: 10.3390/nu11010105. |
| 29357033 | Result | Seyyedebrahimi S, Khodabandehloo H, Nasli Esfahani E, Meshkani R. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. Acta Diabetol. 2018 Apr;55(4):341-353. doi: 10.1007/s00592-017-1098-3. Epub 2018 Jan 22. |
| 37843843 | Result | Gimblet CJ, Kruse NT, Geasland K, Michelson J, Sun M, Mandukhail SR, Wendt LH, Eyck PT, Pierce GL, Jalal DI. Effect of Resveratrol on Endothelial Function in Patients with CKD and Diabetes: A Randomized Controlled Trial. Clin J Am Soc Nephrol. 2024 Feb 1;19(2):161-168. doi: 10.2215/CJN.0000000000000337. Epub 2023 Oct 16. |
| D004700 | Endocrine System Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |