Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.

Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.

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.

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.

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.