Context: There is an increased prevalence of obesity and insulin resistance in African American compared with Caucasian females. Metabolic inflexibility (MI) is the inability to switch the utilization of lipids and carbohydrates in the peripheral tissue (i.e. muscle) based upon substrate availability.

Objective: We examined if MI exists in African American females.

Main Outcome Measures and Design: We measured substrate utilization differences during eucaloric, macronutrient-manipulated diets [high fat (HF, 50% Fat, 35% CHO, 15% Protein) vs. low fat (LF, 30% Fat, 55% CHO, 15% Protein)] between Caucasian and African American women. We also compared differences in substrate utilization in response to insulin infusion during 2-step pancreatic-euglycemic clamps and epinephrine infusion during lipolysis studies. In each study, similar groups of Caucasian and African American women were compared.

Results: Caucasians had significantly higher fat oxidation (FO) (P = 0.01) and lower carbohydrate oxidation (CO) (P < 0.01) during the HF vs. LF diet while no significant differences were observed in African Americans. The African American women also failed to significantly suppress FO during the second step of the pancreatic-euglycemic clamp despite a doubling of their fasting plasma insulin and failed to increase their FO or decrease their CO in response to epinephrine infusion as much as Caucasian women did. The response of free fatty acid turnover rates to insulin and epinephrine stimulation was similar between races.

Conclusion: The impaired substrate utilization observed in African American women during these three studies demonstrates the existence of MI and may contribute to their greater prevalence of obesity and insulin resistance.