Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.

NCT ID: NCT04886973

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-31
• Study Completion Date: 2022-07-29

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.

Detailed Description

An 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids, leucine, isoleucine, and valine, will be administered intravenously. The dose will be calculated considering the 25% of the estimated protein per day. For example, if the patient is 70 kg and the investigators consider 1g/kg/day, the amount of protein to be administered will be 17.5 grams (70 x 0.25 = 17.5 grams). 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. After the administration of the L- amino acid solution, the investigators will take blood samples at 0, 15, 30, 45, 60, 90 and 120 minutes to determine the area under the curve for glucose, insulin, amino acids and branched chain keto acids.

Conditions

Obesity; Insulin Resistance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

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

Intervention Type: OTHER

Intravenous administration of 8% crystalline L-amino acids 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.

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

OTHER

Sponsor Role: lead

Responsible Party

Maria Viridiana Olin Sandoval

Medical Sciences Investigator C

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

MARIA VIRIDIANA OLIN SANDOVAL, Dr

Role: PRINCIPAL_INVESTIGATOR

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Locations

Instituto Nacional de Ciencias Medicas Y Nutricion Salvador Zubiran

México, , Mexico

Countries

Mexico

References

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.

Reference Type: BACKGROUND

PMID: 16424141 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28127425 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16365084 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19356713 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23043162 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27642608 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21423183 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25287287 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25260659 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23057765 (View on PubMed)

Other Identifiers

FNU-3549-20-23-1

Identifier Type: -

Identifier Source: org_study_id