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/m(2)) performed two sessions: (1) euglycemic-hyperinsulinemic clamp (2 mIU/kg of insulin per minute) and (2) similar to 20-hour fast. Clamp MetFlex corresponded to the change in (Delta) respiratory quotient (RQ) (Delta RQ = postchallenge RQ - prechallenge RQ) adjusted for M value and prechallenge RQ. Prolonged fast MetFlex corresponded to the Delta RQ adjusted for the Delta beta-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.