Michielsen M; Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium.
Bekhuis Y; Claes J; Decorte E; De Wilde C; Gojevic T;
Costalunga L; Amyay S; Lazarou V; Daraki D; Kounalaki E; Chatzinikolaou P;
Goetschalckx K; Hansen D; Claessen G; De Craemer M; Cornelissen V

PLoS ONE [Electronic Resource]. 20(9):e0331737, 2025. VI 1

OBJECTIVE: This study investigates the mechanisms behind exercise capacity
in adults with type 2 diabetes mellitus (T2DM), focusing on central and
peripheral components, as described by the Fick equation.

METHODS: A cross-sectional study of 141 adults with T2DM was conducted,
using cardiopulmonary exercise testing, near-infrared spectroscopy (NIRS)
and exercise echocardiography. Participants with sufficient-quality NIRS
data were stratified into tertiles based on percentage predicted VO2peak.
Group comparisons and stepwise regression were used to examine the
contributions of central and peripheral components to VO2peak.

RESULTS: Sixty-seven participants had insufficient quality NIRS data.
Those with lower-quality data were more likely to be female (p < 0.001)
and had a lower exercise capacity (p < 0.001). Among participants with
good-quality NIRS data, those in the lowest fitness tertile were older (p
< 0.01), had a longer diabetes duration (p = 0.04), lower eGFR (p < 0.001)
and more frequent use of beta-blockers (p = 0.02) and diuretics (p =
0.04). Significant differences were observed in peak cardiac output (p <
0.001) and NIRS-derived parameters across fitness groups. Multivariate
regression identified cardiac output as the strongest predictor of
VO2peak, while peripheral oxygen extraction did not improve model
performance.

CONCLUSION: Cardiac output is the primary determinant of exercise
capacity in adults with T2DM. This suggests that muscle perfusion may be
the main limiting factor in relatively fit individuals with T2DM. However,
cardiac output and local muscle perfusion are not directly equivalent, as
mechanical factors, such as intramuscular pressure during high-intensity
exercise, may prevent maximal perfusion.