Metabolic flexibility (MF) refers to the ability to suppress lipid and increase glucose oxidation (as reflected by increase in the respiratory quotient [ΔRQ]) under insulin-stimulated conditions. It is not clear if youth with type 2 diabetes (T2D) and prediabetes have a defect in MF compared with controls. We investigated the determinants of MF in youth with normal weight (NW) and obesity (OB) across the spectrum of glucose tolerance. Youth (n=104; 15.6±1.8 yrs, Tanner stage (TS) II-V) had evaluation of body composition (DXA), visceral fat (VAT) in a subset (MRI), RQ (indirect calorimetry) fasting and during a hyperinsulinemic-euglycemic clamp for measurement of glucose disposal rate (GDR) and insulin sensitivity (IS). Youth with prediabetes and T2D had lower ∆RQ, and lower oxidative and non-oxidative GDR compared to NW with no significant difference in ΔRQ between NW and OB-NGT (Table). ∆RQ correlated with GDR, IS (r=0.3, p=0.02), VAT (r=-.23, p=0.04), and HbA1c (r=-.26, p=0.03) after adjusting for sex, race and TS, but not with % body fat. In multiple regression, Rd (or IS) (β=0.26, p=0.04) and race-ethnicity (β= -0.3, p=0.01) contributed to the variance in ∆RQ (R2=0.25, p=0.005) independent of % body fat, VAT, sex, TS and HbA1c. MF is impaired in youth with prediabetes/T2D compared with NGT-OB and NW in relation to a defect in glucose disposal and appears to be modulated by race-ethnicity (lower in Hispanics).


F. Bacha: Research Support; Self; AstraZeneca, Takeda Development Center Americas, Inc. S.K. Bartz: None. I. Jindal: None. M.R. Puyau: None. A. Adolph: None. S. Sharma: None.


U.S. Department of Agriculture

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at