SYSTEMATIC REVIEW article
Front. Physiol.
Sec. Striated Muscle Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1671926
Effects of Exercise Training on Skeletal Muscle Mitochondrial Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis
Provisionally accepted
- 1Ningbo recovery hospital, Zhejiang, China
- 2Southwest University, Chongqing, China
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Background: Skeletal muscle mitochondrial dysfunction is a key driver of insulin resistance and disease progression in type 2 diabetes mellitus (T2DM), while exercise training has shown potential to improve mitochondrial function. However, existing studies focus on single exercise modalities, lack systematic synthesis of mitochondrial mechanisms, and exhibit conflicting results, highlighting the need for a comprehensive meta-analysis. Methods: Systematic searches were conducted in PubMed, Web of Science, and Scopus for studies involving T2DM patients (≥40 years) with exercise as the primary intervention and mitochondrial outcomes. Methodological quality was assessed via the TESTEX scale, with meta-analysis performed using Stata 17.0. Results: A total of 18 studies (394 participants, 272 in training groups) were included. Exercise significantly enhanced mitochondrial oxidative capacity (SMD = 0.61, 95% CI [0.30, 0.92], driven by citrate synthase [CS] and COX-II), antioxidant capacity (SMD = 1.18, 95% CI [0.50, 1.86], mainly via SOD2), and fusion marker MFN2 (SMD = 0.96, 95% CI [0.63, 1.29]). It tended to increase mitochondrial content (SMD = 0.50, p = 0.091) but with no significant mtDNA/PGC-1α changes. Effective modalities included long-term moderate aerobic training, short-term HIIT, and long-term resistance/combined training. Antidiabetic medications' potential interference was underassessed. Conclusion: Moderate-to-high intensity exercise selectively improves skeletal muscle mitochondrial function in T2DM, particularly oxidative capacity (via CS/COX-II), antioxidant capacity (via SOD2), and mitochondrial fusion (via MFN2). The effect on mitochondrial content is non-significant, and the influence of antidiabetic medications requires further investigation.
Keywords: exercise training, type 2 diabetes mellitus, Mitochondrial function, skeletal muscle, mechanisms
Received: 23 Jul 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Zhu, Zhou, Sun and Si. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Juncheng Si, sijuncheng163@163.com
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