NCT05110274

Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Pennington Biomedical Research Center · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

Summary

This study is designed to test the reliability of a novel procedure for measuring metabolic flexibility, i.e., the ability to quickly adapt macronutrient oxidation to macronutrient availability, in a respiratory chamber. The investigators will compare paired measurements of metabolic flexibility determined 5-7 days apart in a metabolic chamber to assess reliability. The investigators will also compare their novel method of measuring metabolic flexibility in a respiratory chamber with a more convention method, metabolic flexibility during a hyperinsulinemic clamp.

Detailed description

Metabolic flexibility (METFLEX) is the ability to adapt fuel oxidation to fuel availability and energy demands. Impaired METFLEX is associated with weight gain, ectopic lipid deposition, insulin resistance, and the potential development of type 2 diabetes. Even if impaired METFLEX shows promise as an early predictor of future metabolic dysfunction, longitudinal studies have been lacking because of the absence of simple methods for assessing METFLEX. This project will further validate (reproducibility and comparison with hyperinsulinemic-euglycemic clamps) a novel approach for measuring METFLEX recently developed by the PI. METFLEX is commonly measured during a hyperinsulinemic-euglycemic clamp. Yet, this technique is questioned because it relies on a non-physiological stimulus (intravenous glucose and insulin) and inherently suppresses fat oxidation via non physiological hyperinsulinemic conditions. In contrast, impaired fat oxidation in response to a high-fat meal is a more physiological indicator of metabolic inflexibility. The investigators have recently developed a method for measuring METFLEX by assessing the dynamics in respiratory exchange ratio (RER) in response to a high-fat standardized dinner in a whole-body room indirect calorimeter. Securing extramural funding for the aforementioned longitudinal studies employing this novel methodology is presently limited due to a lack of the following preliminary data: 1) quantification of the intra-subject variability of this novel METFLEX measure to perform power calculations (sample size) in large-scale prospective clinical trials, and 2) comparison of our method to a more accepted measurement of METFLEX. The overarching goal of this method development project is to generate reproducibility and validity data of The investigators' new assessment of METFLEX in a whole-body room indirect calorimeter against the METFLEX measured by a hyperinsulinemic-euglycemic clamp.

Conditions

• Metabolism

Interventions

Type	Name	Description
PROCEDURE	Overnight Metabolic Flexibility	Participants will spend 13 hours (overnight) in a metabolic chamber where they will be fed a single high-fat supper meal. Energy expenditure, respiratory exchange ratio (RER), and 12-h oxidation of CHO, fat, and protein will be calculated and used to determine metabolic flexibility, i.e. change in RER from baseline.
PROCEDURE	Clamp Metabolic Flexibility	Metabolic flexibility with be assessed during a 2-step hyperinsulinemic-euglycemic clamp procedure. The clamp will be performed for four hours, two hours at an insulin dose of 10 mU/m\^2/min and two hours at an insulin dose of 80 mU/m\^2/min. Resting metabolic rate will be determined via hood indirect calorimetry at baseline, before insulin onset, and during the final 30 min of each step of the clamp. Metabolic flexibility will be determined by comparing the resting metabolic rate during baseline and during the final 30 min of each step of the clamp.

Timeline

• Start date: 2021-08-26
• Primary completion: 2022-07-08
• Completion: 2022-07-08
• First posted: 2021-11-05
• Last updated: 2023-03-09

Locations

1 site across 1 country: United States