Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.

NCT04886973 | Completed

• 1 other identifier: FNU-3549-20-23-1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

It has been observed that subjects with obesity and insulin resistance have higher concentrations of branched chain amino acids in plasma or serum. However, this association has been established under fasting conditions, so they only give information about a metabolic state and do not reflect the dynamics and flexibility of the metabolism of these amino acids in the absence or presence of insulin resistance. The main aim of this study is to compare the catabolism of branched chain amino acids and their keto acids in subjects with and without insulin resistance, after the infusion of an amino acid solution with high concentration of the branched chain amino acids, leucine, valine, and isoleucine. The results of this project will allow the investigators to understand the dynamics of the branched chain amino acids and their derivatives, and its relationship with insulin resistance, which could eventually be used to design nutritional strategies to treat insulin resistance and thus, delay the development of type 2 diabetes.

Conditions

Obesity; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Area under the curve of branched-chain amino acids.

  Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The branched chain amino acids concentration will be determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS), and the area under the curve will be calculated using the trapezoidal rule.

  2 hours

Secondary Outcomes (6)

• Area under the curve of branched-chain keto acids.

  2 hours

• Area under the curve of insulin.

  2 hours

• Area under the curve of glucose.

  2 hours

• Respiratory quotient.

  2 hours

• Expression of the enzyme branched-chain aminotransferase 2 (BCAT2)

  2 hours

Study Arms (2)

Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2.5

EXPERIMENTAL

Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids. The dose will be calculated considering the 25% of the estimated protein per day (1 g/kg/day). This dose will be placed in a short peripheral intravenous catheter and administered at a rate of 1.5ml per minute, using an infusion pump. The patient will be monitored all the time by a physician.

Other: Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.

Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) < 2.5

EXPERIMENTAL

Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids. The dose will be calculated considering the 25% of the estimated protein per day (1 g/kg/day). This dose will be placed in a short peripheral intravenous catheter and administered at a rate of 1.5ml per minute, using an infusion pump. The patient will be monitored all the time by a physician.

Other: Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.

Interventions

Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids. OTHER

Intravenous administration of 8% crystalline L-amino acids with high concentrations of branched chain amino acids.

Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) < 2.5; Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2.5

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female.
• Adults between 18 and 50 years of age.
• Body Mass Index (BMI) ≥ 18.5 and ≤ 40 kg/m2.
• HOMA index ≥ 2.5
• In the case of women, being in the follicular phase of the menstrual cycle.
• Male and female
• Adults between 18 and 50 years of age.
• Body Mass Index (BMI) ≥ 18.5 and ≤ 40 kg/m2.
• HOMA index \< 2.5
• Blood glucose \< 100 mg/dL
• In the case of women, being in the follicular phase of the menstrual cycle.

You may not qualify if:

• Patients with any type of diabetes.
• Patients with kidney disease diagnosed by any physician.
• Patients with creatinine \> 1.3 mg/dL for men and \> 1.1 mg/dL for women and/or Blood Urea Nitrogen (BUN) \> 20 mg/dL.
• Patients with acquired diseases secondarily producing obesity and diabetes.
• Patients who have suffered a cardiovascular event.
• Weight loss \> 3 kg in the last 3 months.
• Patients with any catabolic diseases.
• Pregnancy status.
• Positive smoking.
• Treatment with any medication (except contraceptives and proton pump inhibitors)
• Having suffered any infection in the last 20 days.

Sponsors & Collaborators

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran: lead

Study Sites (1)

Instituto Nacional de Ciencias Medicas Y Nutricion Salvador Zubiran

México, 14080, Mexico

Location

Related Publications (10)

• Shimomura Y, Yamamoto Y, Bajotto G, Sato J, Murakami T, Shimomura N, Kobayashi H, Mawatari K. Nutraceutical effects of branched-chain amino acids on skeletal muscle. J Nutr. 2006 Feb;136(2):529S-532S. doi: 10.1093/jn/136.2.529S.

  PMID: 16424141 BACKGROUND

• Zhang S, Zeng X, Ren M, Mao X, Qiao S. Novel metabolic and physiological functions of branched chain amino acids: a review. J Anim Sci Biotechnol. 2017 Jan 23;8:10. doi: 10.1186/s40104-016-0139-z. eCollection 2017.

  PMID: 28127425 BACKGROUND

• Brosnan JT, Brosnan ME. Branched-chain amino acids: enzyme and substrate regulation. J Nutr. 2006 Jan;136(1 Suppl):207S-11S. doi: 10.1093/jn/136.1.207S.

  PMID: 16365084 BACKGROUND

• Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311-26. doi: 10.1016/j.cmet.2009.02.002.

  PMID: 19356713 BACKGROUND

• Floegel A, Stefan N, Yu Z, Muhlenbruch K, Drogan D, Joost HG, Fritsche A, Haring HU, Hrabe de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes. 2013 Feb;62(2):639-48. doi: 10.2337/db12-0495. Epub 2012 Oct 4.

  PMID: 23043162 BACKGROUND

• Zhao X, Han Q, Liu Y, Sun C, Gang X, Wang G. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review. J Diabetes Res. 2016;2016:2794591. doi: 10.1155/2016/2794591. Epub 2016 Aug 25.

  PMID: 27642608 BACKGROUND

• Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448-53. doi: 10.1038/nm.2307. Epub 2011 Mar 20.

  PMID: 21423183 BACKGROUND

• Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014 Dec;10(12):723-36. doi: 10.1038/nrendo.2014.171. Epub 2014 Oct 7.

  PMID: 25287287 BACKGROUND

• Serralde-Zuniga AE, Guevara-Cruz M, Tovar AR, Herrera-Hernandez MF, Noriega LG, Granados O, Torres N. Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans. Genes Nutr. 2014 Nov;9(6):431. doi: 10.1007/s12263-014-0431-5. Epub 2014 Sep 27.

  PMID: 25260659 BACKGROUND

• Gunnerud U, Holst JJ, Ostman E, Bjorck I. The glycemic, insulinemic and plasma amino acid responses to equi-carbohydrate milk meals, a pilot- study of bovine and human milk. Nutr J. 2012 Oct 12;11:83. doi: 10.1186/1475-2891-11-83.

  PMID: 23057765 BACKGROUND

MeSH Terms

Conditions

Obesity; Insulin Resistance

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Study Officials

• MARIA VIRIDIANA OLIN SANDOVAL, Dr

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Sciences Investigator C

Model Details: The groups will receive the treatment simultaneously

Study Record Dates

• First Submitted: May 7, 2021
• First Posted: May 14, 2021
• Study Start: March 31, 2022
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: August 2, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)