The Effects of Leucine and Isoleucine on Glucose Metabolism

NCT02634164 | Completed

• 1 other identifier: 17757
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

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. 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. 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).

Conditions

Hyperglycemia

Keywords

leucine; isoleucine

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Change in plasma glucagon (0-150 minutes)

  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)

  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)

  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)

  baseline (0), 2, 4, 6, 8, 10, 30, 32, 34, 36, 38, 40, 60, 90, 120, 150 minutes

Study Arms (4)

control

NO INTERVENTION

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.

Leucine Supplement

EXPERIMENTAL

Control Treatment with Oral Glucose Tolerance Test:

Dietary Supplement: Leucine Supplement

Isoleucine Supplement

EXPERIMENTAL

Isoleucine Combined with Oral Glucose Tolerance Test:

Dietary Supplement: Isoleucine Supplement

Leucine and Isoleucine Supplement

EXPERIMENTAL

Leucine and Isoleucine Combined with Oral Glucose Tolerance Test:

Dietary Supplement: Leucine Supplement combined with Isoleucine Supplement

Interventions

Leucine Supplement 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

Leucine Supplement

Isoleucine Supplement 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.

Isoleucine Supplement

Leucine Supplement combined with Isoleucine Supplement 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.

Leucine and Isoleucine Supplement

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Chronic or acute health problems
• Smoker
• Currently using supplemental BCAA or whey protein -

Sponsors & Collaborators

• Texas Woman's University: lead

Related Publications (8)

• 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.

  PMID: 22293293 BACKGROUND

• 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.

  PMID: 16941278 RESULT

• 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.

  PMID: 20882645 RESULT

• 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.

  PMID: 19013300 RESULT

• 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.

  PMID: 17413098 RESULT

• 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.

  PMID: 19835582 RESULT

• 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.

  PMID: 14651987 RESULT

• 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.

  PMID: 15591158 RESULT

MeSH Terms

Conditions

Hyperglycemia

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Vic Ben-Ezra, PhD

  Texas Woman's University Kinesiology Department

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2015
• First Posted: December 17, 2015
• Study Start: December 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: September 1, 2016
• Last Updated: April 27, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share