Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber
Condition: Metabolism
Study type: Interventional

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.
    

Intervention name(s): Overnight Metabolic Flexibility; Clamp Metabolic Flexibility
Intervention type(s): Procedure; Procedure
Intervention description(s): 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.; 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.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science