Abstract
Background: High-intensity interval training (HIIT) is known to improve insulin sensitivity, glycemic control, and body composition in people with type 2 diabetes mellitus (T2DM). Intermittent hypoxia (i.e., reduced oxygen availability) combined with HIIT may enhance glycemic control through convergent insulin-independent molecular pathways, including AMP-activated protein kinase activation and GLUT 4 translocation. Objective: To evaluate whether 8 weeks of intermittent hypoxia and HIIT, both isolated and combined, improve glucose homeostasis and related health outcomes in individuals with T2DM. Methods: This single-blind, randomized controlled trial will recruit 64 individuals (18-65 years) with T2DM. Participants will be randomly assigned to one of four groups: 1) HIIT with inter-effort recovery hypoxia (inspired oxygen fraction, FiO₂, of 0.135), 2) HIIT in normoxia (FiO₂ = 0.209), 3) passive intermittent hypoxia (FiO₂ = 0.135) or 4) control. Interventions will last 8 weeks, with three sessions per week. HIIT will be performed on a cycle ergometer at intensities based on the heart rate corresponding to the respiratory compensation point and peak power output, as determined by baseline cardiopulmonary exercise testing. The primary outcome is glycated hemoglobin, while secondary measures include glucose homeostasis, cardiorespiratory fitness, cardiovascular health, body composition, and hematological, metabolic, and behavioral outcomes. Generalized linear mixed models (α = 0.05) will be used for statistical analysis. Discussion: This study explores a novel non-pharmacological approach to T2DM management by applying intermittent hypoxia only during recovery periods of HIIT sessions. This method aims to elicit adaptations comparable to conventional intermittent hypoxia, while preserving training quality and offering a more practical, ecologically valid intervention.