Muscle oxygen utilization and ventilatory parameters during exercise in people with cystic fibrosis: Role of HbA_1c

Glycated hemoglobin can interfere with oxygen delivery and CO₂ removal during exercise. Additionally, pancreatic insufficiency increases oxidative stress and exacerbates exercise intolerance in people with cystic fibrosis (PwCF). This investigation sought to test the hypotheses that elevated Hemoglobin A_1c (HbA_1c) can negatively affect exercise parameters in PwCF and that reductions in oxidative stress can improve tissue oxygenation in individuals with elevated HbA_1c.

Twenty four PwCF were divided into two groups; normal HbA1c <5.7% (N-HbA_1c) and elevated HbA_1c >5.7% (E-HbA_1c). A maximal exercise test was conducted to obtain peak oxygen uptake (VO₂peak), VO₂ at ventilatory threshold (VT), ventilatory parameters (V_E/VCO₂ slope and end-tidal CO₂ (petCO₂)). Near-Infrared Spectroscopy (NIRS) was used to assess muscle oxygenated/deoxygenated hemoglobin during exercise. A subset of individuals with E-HbA_1cwere given an antioxidant cocktail (AOC) for 4 weeks to determine the effects on tissue oxygenation during exercise.

A negative relationship between HbA_1c and VO₂peak at VT was observed (r = -0.511; p = 0.018). In addition, a positive relationship between HbA_1c and V_E/VCO₂ slope (r = 0.587;p = 0.005) and a negative relationship between HbA_1c and petCO₂ at maximal exercise (r = -0.472;p = 0.031) was observed. N-HbA_1c had greater VO₂peak (p = 0.021), VO₂ at VT (p = 0.004), petCO₂ (p = 0.002), and lower V_E/VCO₂ slope (p = 0.004) compared with E-HbA_1c. Muscle deoxygenated hemoglobin at VT was higher in N-HbA_1c vs. E-HbA_1c and 4 weeks of AOC improved skeletal muscle utilization of oxygen.

Findings demonstrate that glycated hemoglobin may lead to tissue oxygenation impairment and ventilation inefficiency during exercise in PwCF. In addition, antioxidant supplementation may lead to improved tissue oxygenation during exercise.