Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Lower-limb muscle-specific alterations in type 2 diabetes: A fiber-type-dependent perspective on structural atrophy, functional decline, and targeted resistance training in humans

Articles in Press

Document Type : Review Articles

Authors

Matin Mohyadini 1
Mohammadreza Zarali 2
Esmail Karami 3

1 Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

2 Armed Forces Health Administration of the Islamic Republic of Iran, Tehran, Iran.

3 Clinical Biomechanics and Ergonomics Research Center, Aja University of Medical Sciences, Tehran, Iran.

10.22122/jeoct.2026.592204.1220
Abstract
Type 2 diabetes mellitus (T2DM) adversely affects skeletal muscle, contributing to weakness, functional decline, and reduced mobility. Although lower-limb muscles are essential for locomotion and independence, it remains unclear whether diabetes affects these muscles uniformly or whether certain muscle groups are more vulnerable. Resistance training (RT) is widely recommended for individuals with T2DM. This narrative review synthesizes evidence from human studies on structural and functional alterations in the quadriceps, gastrocnemius, and soleus muscles in adults with T2DM. We propose that fiber-type composition may be a key determinant of muscle-specific vulnerability. Because the soleus is composed predominantly of type I (slow-twitch, oxidative) fibers, which are particularly susceptible to mitochondrial dysfunction, impaired glycogen metabolism, and chronic metabolic stress, we propose the hypothesis that it may undergo earlier and more pronounced deterioration than muscles with a more mixed fiber composition. Current evidence consistently demonstrates reduced quadriceps size, strength, and muscle quality in T2DM, whereas studies of the calf muscles remain limited despite their critical role in gait and balance. Emerging imaging and mechanistic evidence suggest that the soleus may exhibit early diabetes-related microstructural alterations. RT improves muscle strength, physical function, and metabolic health; however, no human study has directly compared the responses of the quadriceps, gastrocnemius, and soleus to the same RT protocol. Overall, available evidence supports regional heterogeneity rather than uniform lower-limb involvement in T2DM. A fiber-type-informed, muscle-specific perspective may improve understanding of diabetes-related muscle dysfunction and guide the development of more targeted resistance training strategies to preserve mobility and functional independence.

What is already known on this subject?

Structural and functional impairments of skeletal muscle are well documented in individuals with T2DM, and resistance training is widely recognized as an effective intervention for improving muscle strength, physical function, and metabolic health. However, previous reviews have generally considered lower-limb muscles as a homogeneous group and have not systematically examined whether fiber-type composition influences muscle-specific vulnerability or adaptive responses to resistance training.

 

What does this study add?

This review proposes a novel fiber-type-informed framework to explain regional heterogeneity in lower-limb muscle involvement in T2DM. We hypothesize that the soleus, because of its predominantly type I fiber composition, may be particularly susceptible to diabetes-related metabolic disturbances and may require a different resistance training strategy than the gastrocnemius or quadriceps. By integrating current human evidence with exercise physiology, this review provides a muscle-specific conceptual framework that may guide future mechanistic studies and the development of more targeted exercise prescriptions.

Keywords

Type 2 diabetes mellitus
Skeletal muscle
Resistance training
Fiber-type composition
Lower-limb muscles
Subjects

Acknowledgements

None.

Funding

None.

Data availability

Review article.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of interest in the present research.

Ethical approval Not applicable.

Informed consent Performed. 

Informed Publication Performed. 

Author contributions 

Conceptualization: M.M, Methodology: M.Z., Software: E.K., Validation: M.M.,; Formal analysis: M.M.,; Investigation: E.K.,; Resources: M.M.,; Data curation: None.,; Writing - original draft: M.M.,; Writing–review & editing M.Z.,; Visualization: E.K.,; Supervision: E.K.; Project administration: M.Z.; Funding acquisition: E.K.        

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Journal of Exercise & Organ Cross Talk

Articles in Press, Accepted Manuscript
Available Online from 14 September 2026

  • Receive Date 18 July 2026
  • Revise Date 28 August 2026
  • Accept Date 14 September 2026

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