Association of metabolic flexibility indexes after an oral glucose tolerance test with cardiometabolic risk factors.

Background & Aims: Metabolic flexibility (MetF) is considered a metabolic health biomarker, as excess body weight is associated with lower MetF. We aimed to identify whether MetF indexes were associated with cardiometabolic risk factors before and after adjustment for body size-related factors (body weight, fat-free mass, and resting metabolic rate).

Methods: We studied 51 participants (55% women; 33.6 ± 8.7 years; 26.3 ± 3.8 kg/m²) who consumed a 75-g glucose load. We measured gas exchange before (fasting) and for 3 h after glucose ingestion. MetF indexes were assessed, including the change after each hour and the 3-hour incremental area under the curve (iAUC) in respiratory exchange ratio (RER). These indexes were then related to cardiometabolic risk factors before and after adjusting for body size-related factors.

Results: MetF indexes correlated with each other (r ≥ 0.51; P < 0.001) and related to body weight (adjusted R ≥ 0.09; P < 0.03). A similar pattern was noted for fat-free mass and resting metabolic rate. MetF, regardless of the index, was not related to cardiometabolic risk factors except to BMI and high-density lipoprotein-cholesterol (HDL-C). The association between BMI and MetF disappeared after adjusting for body size-related factors. Similar adjustments did not modify the association between HDL-C and MetF, especially when approached by the change in RER after the first hour (adjusted R = 0.20-0.22; all P < 0.02).

Conclusions: Inter-individual body size differences fully accounted for the associations between BMI and MetF. However, variability in body size-related factors appeared less relevant in affecting the associations of other cardiometabolic risk factors with MetF.