Effect of L-Citrulline Supplementation on Arginase Activity and Vascular Function in Diabetes

Study Overview
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Brief Summary
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Arginase has recently been implicated in an array of vascular conditions including atherosclerosis , hypertension and vascular complication of diabetes. In this study we will determine of L-citrulline; a natural amino acid that is known to have inhibitory effects on arginase activity, on vascular function in type 2 diabetic patients.

Detailed Description
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Vascular dysfunction is a major cause of morbidity and mortality in diabetic patients. The pathological process is characterized by impaired endothelial cell production of the vasodilator and antiplatelet adhesion factor nitric oxide (NO) and/or decreased NO bioavailability. NO is a major regulator of vascular tone and integrity. In endothelial cells, NO is produced by activity of endothelial NO synthase (eNOS) on its substrate L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes and a variety of other disease conditions. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence increases in arginase activity can decrease tissue and cellular arginine levels, reducing its availability to eNOS and decreasing No production. During diabetes, elevated levels of arginase can compete with NOS for available arginine thus reducing vascular NO. We have recently shown that arginase activity is elevated in diabetes. In this proposal we implement a method of flow mediate dilation (FMD) to assess vascular function in diabetic patients. We will study the relation of our vascular function findings with arginase activity levels. We propose that arginase activity measurements could be novel marker of vascular dysfunction in diabetes. The effect of the natural amino acid supplements (L-citrulline) on levels of arginase activity in diabetic patients and vascular function will also be studied.

Official Title
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Effect of L-Citrulline Supplementation on Arginase Activity and Vascular Function in Type II Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: L-citrulline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes Diabetic state: HbA1c>6 Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Type 2 diabetic patients<br>L-citrulline at a dose of 2000 mg per day for a period of 1 month will be administered to type 2 diabetic patients with HbA1c>6 | Dietary Supplement: L-citrulline<br>* Amino acid supplement<br>|
| Experimental: Healthy volunteers<br>L-citrulline at a dose of 2000 mg per day for a period of 1 month will be administered to non-diabetic healthy volunteers | Dietary Supplement: L-citrulline<br>* Amino acid supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| arginase activity | Levels of arginase activity enzyme will be measured in plasma in subjects before and after l-citrulline supplementation | 1 month | 
| Vascular function | forearm vascular function will be assessed by flow mediated dilation of brachial blood vessels before and after L-citrulline supplementation | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular dysfunction, L-citrulline, arginase