The Effects of Leucine and Isoleucine on Glucose Metabolism

Study Overview
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Brief Summary
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Diabetes is classified as an impairment of the body's ability to control blood glucose levels. Uncontrolled hyperglycemia can give rise to macrovascular (i.e., heart disease and stroke) and microvasculature damage such as retinopathy, nephropathy and neuropathy. These comorbidities may definitively reduce quality of life. Hypotheses to be tested: The ingestion of amino acids L-Isoleucine and L-Leucine at a therapeutic dose prior to a glucose load will concurrently and independently improve glucose tolerance. The ingestion of L-Isoleucine and L-Leucine separately or together will have a minimal effect on incretin responses of Glucagon-like peptide-1 and Glucose-dependent insulinotropic peptide (GLP-1, GIP).

Detailed Description
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Specific Aims and Hypothesis Diabetes is classified as an impairment of the body's ability to control blood glucose levels. Uncontrolled hyperglycemia can give rise to macrovascular (i.e., heart disease and stroke) and microvasculature damage such as retinopathy, nephropathy and neuropathy. These comorbidities may definitively reduce quality of life. Hypotheses to be tested: The ingestion of amino acids L-Isoleucine and L-Leucine at a therapeutic dose prior to a glucose load will concurrently and independently improve glucose tolerance. The ingestion of L-Isoleucine and L-Leucine separately or together will have a minimal effect on incretin responses (GLP-1, GIP). Specific Aims: Specific Aim I will test the hypothesis that the ingestion of amino acids L-Isoleucine and L-Leucine at a therapeutic dose prior to a glucose load will concurrently and independently improve glucose tolerance. Specific Aim II will test the hypothesis that the ingestion of L-Isoleucine and L-Leucine will have a minimal effect on incretin responses in conjunction with prior research.

Official Title
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The Effects of Leucine and Isoleucine on Glucose Metabolism

Conditions
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Hyperglycemia

Intervention / Treatment
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* Dietary Supplement: Leucine Supplement
* Dietary Supplement: Isoleucine Supplement
* Dietary Supplement: Leucine Supplement combined with Isoleucine Supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age range of 20 to 40 years of age (sedentary lifestyle) Participants whom exercise less than the American College of Sports Medicine recommendation of weekly physical activity levels or are completely sedentary may be admitted into the study Apparently healthy Currently not using supplemental branch chain amino acids (BCAA) or whey protein Non-smoking Exclusion Criteria: Chronic or acute health problems Smoker Currently using supplemental BCAA or whey protein -

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control<br>Control Treatment with Oral Glucose Tolerance Test: Blood glucose and insulin will be obtained following the protocol of Eicher et al (4). Participants will ingest a Placebo (inert, calorie free, stevia sweetener) with blood collections at 0,2,4,6,8,10,30 prior to a standard 75 g glucose solution, followed by blood collections at 0,2,4,6,8,10,30,60,90,120 minutes post glucose ingestion. A total of 16 blood collections will be taken. | |
| Experimental: Leucine Supplement<br>Control Treatment with Oral Glucose Tolerance Test: | Dietary Supplement: Leucine Supplement<br>* For this visit participants will ingest a powdered form of Leucine in the amount of 0.3g/kg of lean body mass weight with water (150 mL) with additional water if needed to ensure dose is fully consumed. The amino acid solution will be ingested 30 min prior to 75 g glucose solution<br>|
| Experimental: Isoleucine Supplement<br>Isoleucine Combined with Oral Glucose Tolerance Test: | Dietary Supplement: Isoleucine Supplement<br>* For this visit participants will ingest a powdered form of Isoleucine in the amount of 0.3g/kg of lean body mass weight with water (150 mL) with additional water if needed to ensure dose is fully consumed. The amino acid solution will be ingested 30 min prior to 75 g glucose solution.<br>|
| Experimental: Leucine and Isoleucine Supplement<br>Leucine and Isoleucine Combined with Oral Glucose Tolerance Test: | Dietary Supplement: Leucine Supplement combined with Isoleucine Supplement<br>* For this visit participants will ingest a powdered form of Leucine and Isoleucine in the amount of 0.3g/kg of lean body mass weight (equal in total dosage to other treatments) with water (150 mL) with additional water if needed to ensure dose is fully consumed. The amino acid solution will be ingested 30 min prior to 75 g glucose solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma glucose (0-150 minutes) | Blood collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 
| Change in plasma insulin (0-150 minutes) | Blood collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 
| Change in plasma GIP (0-150 minutes) | Blood Collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 
| Change in plasma GLP-1 (0-150 minutes) | Blood collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma glucagon (0-150 minutes) | Blood collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 
| Change in plasma c-peptide (0-150 minutes) | Blood Collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 
| Change in plasma L-Leucine (0-150 minutes) | Blood Collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 
| Change in plasma L-Isoleucine (0-150 minutes) | Blood Collections | baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leucine, isoleucine