Fat And Carbohydrate Oxidation During Cardiopulmonary Exercise Test In Childhood Acute Lymphoblastic Leukemia Survivors

Abstract

PURPOSE: Analyses of indirect calorimetry during cardiopulmonary exercise tests (CPET) have the potential to bring new evidence about the metabolic health of childhood acute lymphoblastic leukemia (ALL) survivors. To propose a better knowledge of survivors’ metabolic health, we aimed to compare their carbohydrate and fat oxidation during a CPET. Moreover, we explored the long-term effects of doxorubicin and dexrazoxane on survivors’ metabolic health. METHODS: A total of 250 childhood ALL survivors were categorized into three groups depending on their prognostic risk (i.e., standard risk (SR), high risk with and without cardio-protective agent dexrazoxane (HR + DEX and HR)). They underwent a CPET on ergocycle to assess their oxygen consumption and their carbon dioxide production. Carbohydrate and fat oxidation rates were determined using the Peronnet and Massicotte’s equation. For each childhood ALL survivor, we produced a third-degree polynomial equation in order to obtain the best-fit curve for fat and carbohydrate oxidation rate (mg/min) against exercise intensity (%VO2peak). We also used them to compare carbohydrate and fat oxidation over a range of exercise intensities and to determine the maximal fat oxidation (MFO) rate and the peak fat oxidation (Fatmax) rate. MFO and Fatmax comparisons were made using one-way ANOVA. Multiple linear regression analysis was used to quantify each variable’s influence on the MFO and the Fatmax. RESULTS: We observed that MFO parameter was not different between the groups (p = 0.078) (SR = 273.7 ± 99.5 mg·min-1; HR + DEX = 247.3 ± 93.2 mg·min-1; and HR = 239.2 ± 86.0 mg·min-1). There was no difference between the groups for the Fatmax parameter (p = 0.865) (SR = 35.1 ± 7.4%; HR + DEX = 34.6 ± 7.5%; and HR = 35.7 ± 8.1%) and 14% of the variability was explained by the maximum oxygen uptake, sex and obesity. CONCLUSIONS: This study shows that although childhood ALL survivors have a reduced fat oxidation rates, that does not depend on the prognostic risk group. However, we observed a trend that suggests that the reduction of fat oxidation is doxorubicin dose-dependent and that the dexrazoxane treatment has the potential to limit these effects. Our study highlights that survivors’ metabolic health and substrate oxidation are compromised during a maximal cardiopulmonary exercise test.