The Effects of Leucine and Isoleucine on Glucose Metabolism

NCT ID: NCT02634164

Last Updated: 2017-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2016-09-30

Brief Summary

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:

1. 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.

2. 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

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:

1. 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.

2. The ingestion of L-Isoleucine and L-Leucine separately or together will have a minimal effect on incretin responses (GLP-1, GIP).

Specific Aims:

1. 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.

2. 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.

Conditions

Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Leucine Supplement

Control Treatment with Oral Glucose Tolerance Test:

Group Type: EXPERIMENTAL

Leucine Supplement

Intervention Type: DIETARY_SUPPLEMENT

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

Isoleucine Supplement

Isoleucine Combined with Oral Glucose Tolerance Test:

Group Type: EXPERIMENTAL

Isoleucine Supplement

Intervention Type: DIETARY_SUPPLEMENT

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.

Leucine and Isoleucine Supplement

Leucine and Isoleucine Combined with Oral Glucose Tolerance Test:

Group Type: EXPERIMENTAL

Leucine Supplement combined with Isoleucine Supplement

Intervention Type: DIETARY_SUPPLEMENT

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.

Interventions

Leucine Supplement

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

Intervention Type: DIETARY_SUPPLEMENT

Isoleucine Supplement

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.

Intervention Type: DIETARY_SUPPLEMENT

Leucine Supplement combined with Isoleucine Supplement

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. age range of 20 to 40 years of age

2. (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

3. Apparently healthy

4. Currently not using supplemental branch chain amino acids (BCAA) or whey protein

5. Non-smoking

Exclusion Criteria

1. Chronic or acute health problems

2. Smoker

3. Currently using supplemental BCAA or whey protein -

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Texas Woman's University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vic Ben-Ezra, PhD

Role: STUDY_CHAIR

Texas Woman's University Kinesiology Department

References

Yoshizawa F. New therapeutic strategy for amino acid medicine: notable functions of branched chain amino acids as biological regulators. J Pharmacol Sci. 2012;118(2):149-55. doi: 10.1254/jphs.11r05fm. Epub 2012 Jan 27.

Reference Type: BACKGROUND

PMID: 22293293 (View on PubMed)

Nuttall FQ, Schweim KJ, Gannon MC. Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations. Horm Metab Res. 2006 Aug;38(8):518-23. doi: 10.1055/s-2006-949523.

Reference Type: RESULT

PMID: 16941278 (View on PubMed)

Gannon MC, Nuttall FQ. Amino acid ingestion and glucose metabolism--a review. IUBMB Life. 2010 Sep;62(9):660-8. doi: 10.1002/iub.375.

Reference Type: RESULT

PMID: 20882645 (View on PubMed)

Kalogeropoulou D, Lafave L, Schweim K, Gannon MC, Nuttall FQ. Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose. Metabolism. 2008 Dec;57(12):1747-52. doi: 10.1016/j.metabol.2008.09.001.

Reference Type: RESULT

PMID: 19013300 (View on PubMed)

Nilsson M, Holst JJ, Bjorck IM. Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr. 2007 Apr;85(4):996-1004. doi: 10.1093/ajcn/85.4.996.

Reference Type: RESULT

PMID: 17413098 (View on PubMed)

Petersen BL, Ward LS, Bastian ED, Jenkins AL, Campbell J, Vuksan V. A whey protein supplement decreases post-prandial glycemia. Nutr J. 2009 Oct 16;8:47. doi: 10.1186/1475-2891-8-47.

Reference Type: RESULT

PMID: 19835582 (View on PubMed)

Doi M, Yamaoka I, Fukunaga T, Nakayama M. Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1111-7. doi: 10.1016/j.bbrc.2003.11.039.

Reference Type: RESULT

PMID: 14651987 (View on PubMed)

Nishitani S, Takehana K, Fujitani S, Sonaka I. Branched-chain amino acids improve glucose metabolism in rats with liver cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2005 Jun;288(6):G1292-300. doi: 10.1152/ajpgi.00510.2003. Epub 2004 Dec 9.

Reference Type: RESULT

PMID: 15591158 (View on PubMed)

Other Identifiers

17757

Identifier Type: -

Identifier Source: org_study_id