ETD

• cardiopulmonary exercise test
• effort intolerance
• lipid oxidation
• oxygen uptake
• type 2 diabetes

Background and aims: Patients with type 2 diabetes (T2D) suffer from effort intolerance and reduced oxygen uptake that are not fully explained by cardiopulmonary capacity. We investigated the effect of T2D on fuel selection and oxidation during progressive exercise.
Methods: We conducted an analysis of 95 patients with T2D and 95 age-, sex-, and weight–matched control participants with normal glucose tolerance, who underwent a maximal cardiopulmonary exercise test (CPET) combined with stress echocardiography. We applied indirect calorimetry to breath-by-breath gas exchange to estimate lipid (FATox) and carbohydrate oxidation (CHOox) rates during incremental exercise.
Results: Patients with T2D presented reduced oxygen uptake at peak exercise (18.25±4.11 vs 21.92±8.48 mg/kg/min; p < 0.001) compared to controls, reached a lower workload (112.4±30.6 W vs 136.1±59.0 W, p < 0.001) and showed impaired peripheral oxygen uptake during exercise (11.77±3.04 vs 13.00±4.14 mL/dL; p = 0.028). The analysis of oxidative substrate utilisation highlighted lower absolute and relative rates FATox throughout the test (p < 0.005) with reduced maximal fat oxidation rate (MFO) normalised for fat free mass (4.44±1.30 vs 5.35±2.23 mg/min/Kg; p < 0.001) in patients with T2D, while CHOox were similar (p > 0.05). We found a strong direct linear relationship between MFO and VO2peak (R2=0.34, p < 0.001) in the whole population as well as in both T2D patients with T2D and controls and in both patients with T2D and in the control group.
Conclusion: Patients with T2D exhibit a reduction in oxygen uptake, associated with impaired peripheral oxygen extraction and skeletal muscle lipid oxidation, suggesting that mitochondrial metabolic dysfunction may contribute to exercise intolerance in this population.