Direct Relationship Between Metabolic Flexibility Measured During Glucose Clamp and Prolonged Fast in Men

Objective: This study aimed to determine the relationship between metabolic flexibility (MetFlex) measured during a euglycemic-hyperinsulinemic clamp and a prolonged fast. This study also analyzed the association between MetFlex and metabolic health. Methods: Eighteen healthy men (mean [SD]: 22 [2] years old; BMI: 22 [1] kg/m²) performed two sessions: (1) euglycemic-hyperinsulinemic clamp (2 mIU/kg of insulin per minute) and (2) ~20-hour fast. Clamp MetFlex corresponded to the change in (Δ) respiratory quotient (RQ) (ΔRQ = postchallenge RQ − prechallenge RQ) adjusted for M value and prechallenge RQ. Prolonged fast MetFlex corresponded to the ΔRQ adjusted for the Δβ-hydroxybutyrate and prechallenge RQ. Results: MetFlex during the clamp related directly with MetFlex during prolonged fast (r = 0.59, P = 0.014). Using the median of MetFlex for each challenge, this study split participants into high or low MetFlex. Participants with high or low MetFlex to both challenges were identified. Participants with high MetFlex had 3% lower serum low-density lipoprotein cholesterol than participants with low MetFlex (P = 0.021). Conclusions: Measuring MetFlex during a clamp or a prolonged fast produces similar results, despite challenging the oxidation of different substrates. An impaired MetFlex in response to these challenges may be an early event in the development of abnormal lipid metabolism.