Effects of Different Aerobic Exercise Programs and a Dietary Intervention on Mitochondrial Function in Adults with Type 2 Diabetes Mellitus

Abstract

Introduction. Mitochondrial function serves as a critical determinant of cellular health,influencing energy production, metabolic regulation, and susceptibility to variousdiseases. Type 2 Diabetes Mellitus (T2DM) is characterized by a reduction inmitochondrial function; thus, aerobic exercise interventions have been proposed toimprove mitochondrial respiratory function in this population. Both High-IntensityInterval Training (HIIT) and Moderate Intensity Continuous Training (MICT) have beenproposed as effective approaches. Additionally, dietary interventions have beenrecommended for T2DM patients to promote fat loss and improve insulin sensitivity,although its impact on mitochondrial function and potential interaction with physicalexercise remains unknown. Therefore, the present study aimed to compare the isolatedand combined effects of two different aerobic exercise programs (HIIT vs. MICT) and adietary intervention on mitochondrial function in T2DM patients.Methods. Thisrandomized controlled trial was conducted with 102 obese or overweightadults with T2DM (51 females; 56±7 years; mean body mass index = 35±4 kg/m2) whowere randomized into six groups: HIIT (10x1-minute intervals of pedalling at 90% of peakpower output, n=18), MICT (continuous pedalling at 10% above the first ventilatorythreshold for 50 minutes, n=18), Diet (Mediterranean pattern-based diet individualizedfor body fat loss, n=14), HIIT+Diet (n=20), MICT+Diet (n=13), or a control group (CG,n=19). Exercise interventions consisted of 3 supervised sessions per week for 12 weeks,whereas diet interventions involved personal interviews every 2 weeks for 12 weeks providing a weekly meal plan. Mitochondrial function was evaluated before and afterthe 12-week intervention in permeabilized skeletal muscle fibres from the VastusLateralis using high-resolution respirometry (Oroboros Instruments, Innsbruck, Austria).The measurement protocol began with the addition of pyruvate, malate, and glutamate,followed by ADP and Mg to assess complex I-linked respiratory capacity (CI), and thensuccinate was added to induce maximal respiratory capacity (CI+II). A 2 (pre vs. post) x3 (HIIT vs. MICT vs. Non-exercise) x 2 (Diet vs. No-diet) mixed factorial ANOVA withBonferroni post hoc comparisons was employed.Results and Conclusions. A significant time x exercise group interaction was found forCI (F=3.990, η2p=0.077, p=0.022) and CI+II (F=5.436, η2p=0.102, p=0.006). Post-hocanalysis revealed significant improvements in the HIIT group (+40.6%, p=0.016; and+44.4%, p=0.001 for CI and CI+II, respectively) and the MICT group (+83.3%, p<0.001;and+77.6%, p<0.001 for CI and CI+II, respectively). No significant time x exercise x dietgroup or time x diet group interactions were found. These results suggest that exercisehas a positive effect on mitochondrial function, with MICT intervention exhibiting thegreatest percentage of improvement. Additionally, a dietary intervention, although itmay have health benefitsin other variables, does not provide additional benefits beyondthe effects of exercise on mitochondrial function in T2DM patients. This study is part ofthe MITOX project funded by an internal call of the Biomedical Research and InnovationInstitute of Cádiz(INiBICA) (grant number: PP11-007-2023). Manuel Costilla issupportedby a predoctoral grant from the Spanish Ministry of Universities (grant number:FPU22/03208)