Clinical trial NCT04886973: Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.
Official title: Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Insulin Resistance
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2021-05-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The groups will receive the treatment simultaneously
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria for cases (subjects with insulin resistance).

* 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.

Inclusion criteria for controls (subjects without insulin resistance).

* 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.

Primary outcomes:
measure: Area under the curve of branched-chain amino acids.
timeFrame: 2 hours
Secondary outcomes:
measure: Area under the curve of branched-chain keto acids.
timeFrame: 2 hours
measure: Area under the curve of insulin.
timeFrame: 2 hours
measure: Area under the curve of glucose.
timeFrame: 2 hours
measure: Respiratory quotient.
timeFrame: 2 hours
measure: Expression of the enzyme branched-chain aminotransferase 2 (BCAT2)
timeFrame: 2 hours
measure: Expression of the enzyme branched-chain keto acid dehydrogenase (BCKDH)
timeFrame: 2 hours
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: Instituto Nacional de Ciencias Medicas Y Nutricion Salvador Zubiran
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: MARIA VIRIDIANA OLIN SANDOVAL, Dr
role: PRINCIPAL_INVESTIGATOR
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