Decreased HOMA-IR levels after physical exercise as a therapy to reduce insulin resistance: A systematic review
Abstract
A sedentary lifestyle can increase metabolic diseases such as diabetes mellitus. The aim of this study was to determine how physical activity reduces insulin resistance by reducing HOMA-IR levels. This study also provides a theoretical basis for physical exercise in preventing insulin resistance in humans. For our systematic review, we searched several literature databases (PubMed, Web of Science, and ScienceDirect) for articles published in the past five years that examined physical activity and HOMA-IR. A total of 422 published papers were located using the Web of Science, Pubmed, and Science Direct databases. Ten papers that satisfied the inclusion criteria were chosen and examined for this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used in this study to assess standard operating procedures. It has been demonstrated that regular exercise lowers insulin resistance by lowering HOMA-IR values. It has been proven that physical exercise is the best therapy for people with metabolic diseases, especially insulin resistance. Physical exercise has been shown to significantly reduce insulin resistance by decreasing HOMA-IR levels. Therefore, regular physical exercise is highly recommended as the best therapy for insulin resistance in humans.
Downloads
-
Abstract0
-
PDF0
References
1. Amanat, S., Sinaei, E., Panji, M., MohammadporHodki, R., Bagheri-Hosseinabadi, Z., Asadimehr, H., … Dianatinasab, A. (2020). A Randomized Controlled Trial on the Effects of 12 Weeks of Aerobic, Resistance, and Combined Exercises Training on the Serum Levels of Nesfatin-1, Irisin-1 and HOMA-IR. Frontiers in Physiology, 11, 1–14. https://doi.org/10.3389/fphys.2020.562895
2. Asfaw, M. S., & Dagne, W. K. (2022). Physical activity can improve diabetes patients’ glucose control; A systematic review and meta-analysis. Heliyon, 8(12), 1-12. https://doi.org/10.1016/j.heliyon.2022.e12267
3. Ayubi, N., Wibawa, J. C., Lesmana, H. S., Callixte, C., & Dafun, P. B. (2024). Physical exercise induces increased translocation of type 4 glucose transporters (GLUT4): a systematic review. Retos, 59, 1003–1008. https://doi.org/10.47197/retos.v59.104078
4. Bacchi, E., Negri, C., Zanolin, M. E., Milanese, C., Faccioli, N., Trombetta, M., … Moghetti, P. (2012). Metabolic effects of aerobic training and resistance training in type 2 diabetic subjects: A randomized controlled trial (the RAED2 study). Diabetes Care, 35(4), 676–682. https://doi.org/10.2337/dc11-1655
5. Balakrishnan, R., & Thurmond, D. C. (2022). Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance. International Journal of Molecular Sciences, 23(9), 1-24. https://doi.org/10.3390/ijms23094636
6. Bradley, H., Shaw, C. S., Bendtsen, C., Worthington, P. L., Wilson, O. J., Strauss, J. A., … Wagenmakers, A. J. M. (2015). Visualization and quantitation of GLUT4 translocation in human skeletal muscle following glucose ingestion and exercise. Physiological Reports, 3(5), 1–11. https://doi.org/10.14814/phy2.12375
7. Calcaterra, V., Magenes, V. C., Bianchi, A., Rossi, V., Gatti, A., Marin, L., Vandoni, M., & Zuccotti, G. (2024). How Can Promoting Skeletal Muscle Health and Exercise in Children and Adolescents Prevent Insulin Resistance and Type 2 Diabetes?. Life, 14(9), 1-30. https://doi.org/10.3390/life14091198
8. Care, D., & Suppl, S. S. (2024). 3. Prevention or Delay of Diabetes and Associated Comorbidities: Standards of Care in Diabetes—2024. Diabetes Care, 47, 43–51. https://doi.org/10.2337/dc24-S003
9. Yu, Y. T., Fu, Y. H., Chen, Y. H., Fang, Y. W., & Tsai, M. H. (2025). Effect of dietary glycemic index on insulin resistance in adults without diabetes mellitus: a systematic review and meta-analysis. Frontiers in Nutrition, 12, 1-12. https://doi.org/10.3389/fnut.2025.1458353
10. Chen, M., Zhu, J. Y., Mu, W. J., Luo, H. Y., Li, Y., Li, S., Yan, L. J., Li, R. Y., & Guo, L. (2023). Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice. Nature Communications, 14(1), 1–19. https://doi.org/10.1038/s41467-023-44242-7
11. Das, A. M., Steuerwald, U., & Illsinger, S. (2010). Inborn errors of energy metabolism associated with myopathies. Journal of Biomedicine and Biotechnology, 2010, 1-21. https://doi.org/10.1155/2010/340849
12. Garg, V., Ghay, R., Goyal, G., & Saini, R. V. (2025). Exploring the Role of Acute Exercise-Induced Myokine Release in Glucose Metabolism and Insulin Sensitivity in Healthy and Diabetic Individuals. Cureus, 17(2), 1–10. https://doi.org/10.7759/cureus.78991
13. Gejl, K. D., Andersson, E. P., Nielsen, J., Holmberg, H. C., & Ørtenblad, N. (2020). Effects of Acute Exercise and Training on the Sarcoplasmic Reticulum Ca2+ Release and Uptake Rates in Highly Trained Endurance Athletes. Frontiers in Physiology, 11, 1–11. https://doi.org/10.3389/fphys.2020.00810
14. Ghahfarrokhi, M. M., Shirvani, H., Rahimi, M., Bazgir, B., Shamsadini, A., & Sobhani, V. (2024). Feasibility and preliminary efficacy of different intensities of functional training in elderly type 2 diabetes patients with cognitive impairment: a pilot randomised controlled trial. BMC Geriatrics, 24(1), 1–15. https://doi.org/10.1186/s12877-024-04698-8
15. Ha, M. S., Yook, J. S., & Lee, M. (2024). Effects of 16-Week Exercise on Insulin, HOMA-IR, and Glucose Levels in Obese Childhood. Exercise Science, 33(3), 310–316. https://doi.org/10.15857/ksep.2024.00423
16. Iaccarino, G., Franco, D., Sorriento, D., Strisciuglio, T., Barbato, E., & Morisco, C. (2021). Modulation of Insulin Sensitivity by Exercise Training: Implications for Cardiovascular Prevention. Journal of Cardiovascular Translational Research, 14(2), 256–270. https://doi.org/10.1007/s12265-020-10057-w
17. Kartinah, N. T., Rusli, H., Ilyas, E. I. I., Andraini, T., & Paramita, N. (2024). High-intensity interval training increases AMPK and GLUT4 expressions via FGF21 in skeletal muscles of diabetic rats. Journal of Advanced Biotechnology and Experimental Therapeutics, 7(1), 136–146.
18. Katsuki, A., Sumida, Y., Gabazza, E. C., Murashima, S., Furuta, M., Araki-Sasaki, R., … Adachi, Y. (2001). Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes Care, 24(2), 362–365. https://doi.org/10.2337/diacare.24.2.362
19. Khalili, D., Khayamzadeh, M., Kohansal, K., Ahanchi, N. S., Hasheminia, M., Hadaegh, F., … Habibi-Moeini, A. S. (2023). Are HOMA-IR and HOMA-B good predictors for diabetes and pre-diabetes subtypes? BMC Endocrine Disorders, 23(1), 1–9. https://doi.org/10.1186/s12902-023-01291-9
20. Lee, J., Kim, M., Jang, J.-Y., & Oh, C.-M. (2023). Assessment HOMA as a predictor for new onset diabetes mellitus and diabetic complications in non-diabetic adults: a KoGES prospective cohort study. Clinical Diabetes and Endocrinology, 9(1), 1–8. https://doi.org/10.1186/s40842-023-00156-3
21. Lee, S. H., Park, S. Y., & Choi, C. S. (2022). Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes and Metabolism Journal, 46(1), 15–37. https://doi.org/10.4093/DMJ.2021.0280
22. Li, S., Yuan, S., Zhang, J., Xu, F., & Zhu, F. (2024). The effect of periodic resistance training on obese patients with type 2 diabetic nephropathy. Scientific Reports, 14(1), 1–12. https://doi.org/10.1038/s41598-024-53333-4
23. Loyd, C., Magrisso, I. J., Haas, M., Balusu, S., Krishna, R., Itoh, N., … Habegger, K. M. (2016). Fibroblast growth factor 21 is required for beneficial effects of exercise during chronic high-fat feeding. Journal of Applied Physiology, 121(3), 687–698. https://doi.org/10.1152/japplphysiol.00456.2016
24. Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985). Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28(7), 412–419. https://doi.org/10.1007/BF00280883
25. Meng, C., Yucheng, T., Shu, L., & Yu, Z. (2022). Effects of school-based high-intensity interval training on body composition, cardiorespiratory fitness and cardiometabolic markers in adolescent boys with obesity: a randomized controlled trial. BMC Pediatrics, 22(1), 1–11. https://doi.org/10.1186/s12887-021-03079-z
26. Mezghani, N., Ammar, A., Boukhris, O., Abid, R., Hadadi, A., Alzahrani, T. M., … Chtourou, H. (2022). The Impact of Exercise Training Intensity on Physiological Adaptations and Insulin Resistance in Women with Abdominal Obesity. Healthcare, 10(12), 1–17. https://doi.org/10.3390/healthcare10122533
27. Michishita, R., Shono, N., Kasahara, T., & Tsuruta, T. (2008). Effects of low intensity exercise therapy on early phase insulin secretion in overweight subjects with impaired glucose tolerance and type 2 diabetes mellitus. Diabetes Research and Clinical Practice, 82(3), 291–297. https://doi.org/10.1016/j.diabres.2008.08.013
28. Misra, A., Alappan, N. K., Vikram, N. K., Goel, K., Gupta, N., Mittal, K., … Luthra, K. (2008). Effect of supervised progressive resistance-exercise training protocol on insulin sensitivity, glycemia, lipids, and Body composition in asian indians with type 2 diabetes. Diabetes Care, 31(7), 1282–1287. https://doi.org/10.2337/dc07-2316
29. Moffa, S., Sorice, G. P., Di Giuseppe, G., Cinti, F., Ciccarelli, G., Soldovieri, L., Brunetti, M., Sonnino, R., Nista, E. C., Gasbarrini, A., Pontecorvi, A., Mezza, T., & Giaccari, A. (2025). A single bout of physical exercise improves 1-hour post-load plasma glucose in healthy young adults. Journal of Endocrinological Investigation, 48(2), 455–464. https://doi.org/10.1007/s40618-024-02438-8
30. Nellaiappan, K., Preeti, K., Khatri, D. K., & Singh, S. B. (2021). Diabetic Complications: An Update on Pathobiology and Therapeutic Strategies. Current Diabetes Reviews, 18(1), 1–14. https://doi.org/10.2174/1573399817666210309104203
31. Okabe, K., Yaku, K., Tobe, K., & Nakagawa, T. (2019). Implications of altered NAD metabolism in metabolic disorders. Journal of Biomedical Science, 26(1), 1–13. https://doi.org/10.1186/s12929-019-0527-8
32. Richter, E. A., & Hargreaves, M. (2013). Exercise, GLUT4, and skeletal muscle glucose uptake. Physiological Reviews, 93(3), 993–1017. https://doi.org/10.1152/physrev.00038.2012
33. Sakamoto, K., & Holman, G. D. (2008). Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic. American Journal of Physiology - Endocrinology and Metabolism, 295(1), 29–37. https://doi.org/10.1152/ajpendo.90331.2008
34. Sorriento, D., Di Vaia, E., & Iaccarino, G. (2021). Physical Exercise: A Novel Tool to Protect Mitochondrial Health. Frontiers in Physiology, 12, 1–14. https://doi.org/10.3389/fphys.2021.660068
35. Strasser, B., & Pesta, D. (2013). Resistance training for diabetes prevention and therapy: Experimental findings and molecular mechanisms. BioMed Research International, 2013(4), 1-8. https://doi.org/10.1155/2013/805217
36. Takahashi, A., Furuta, H., Nishi, H., Kamei, H., Takahashi, S. I., & Hakuno, F. (2025). Insulin Receptor Substrate-2 Regulates the Secretion of Growth Factors in Response to Amino Acid Deprivation. International Journal of Molecular Sciences, 26(2), 1-15. https://doi.org/10.3390/ijms26020841
37. Thong, F. S. L., Bilan, P. J., & Klip, A. (2007). The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic. Diabetes, 56(2), 414–423. https://doi.org/10.2337/db06-0900
38. Tokumitsu, H., & Sakagami, H. (2022). Molecular Mechanisms Underlying Ca2+/Calmodulin-Dependent Protein Kinase Kinase Signal Transduction. International Journal of Molecular Sciences, 23(19), 1-19. https://doi.org/10.3390/ijms231911025
39. Tambuwal, U. M., Ahmad, S. A., Hayatu, U., Sadiq, M. A., Kolawale, J. A., Bello, S. K., & Umar, A. F. (2024). Exploring the Effect of Exercise versus Metformin on Insulin Resistance amongst Nigerians with Pre-diabetes: A Randomised Controlled Trial. The Nigerian Postgraduate Medical Journal, 31(3), 274–279. https://doi.org/10.4103/npmj.npmj_148_24
40. Wheeler, D. C., James, J., Patel, D., Viljoen, A., Ali, A., Evans, M., … Wilding, J. (2020). SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes. Diabetes Therapy, 11(12), 2757–2774. https://doi.org/10.1007/s13300-020-00930-x
41. World Health Organization. (2021). Global health estimates: Leading causes of death and disability. https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death
42. Wang, X., Zheng, M., Qin, S., Li, Y., & Xu, H. (2025). Effects of aerobic vs combined aerobic and resistance exercise training on maternal glucose metabolism, sympathetic nervous system control and cardiovascular hemodynamics in women with overweight/obesity during pregnancy. Ginekologia Polska, 96(3), 184–191. https://doi.org/10.5603/gpl.102215
43. Yunn, N. O., Kim, J., Ryu, S. H., & Cho, Y. (2023). A stepwise activation model for the insulin receptor. Experimental and Molecular Medicine, 55(10), 2147–2161. https://doi.org/10.1038/s12276-023-01101-1
The works and papers that are published in this Journal are subject to the following terms:
1. The Publication Service of the University of Murcia (the publisher) has the Publication Rights (Copyright) to the published papers and works, and favors and permits the reusing of the same under the license indicated in point 2.
© Servicio de Publicaciones, Universidad de Murcia, 2013
2. The papers and works are to be published in the digital edition of the Journal under the license Creative Commons Reconocimiento-No Comercial-Sin Obra Derivada 3.0 España (legal text). The copying, using, spreading, transmitting and publicly displaying of the papers, works or publication are permitted as long as: i) the authors and original sources (Journal, publisher and URL of the publication) are quoted; ii) it is not used for commercial benefit; iii) the existence and specifications of this users license are mentioned.
3. Conditions of Self-Archiving. It is permitted and encouraged that the authors spread electronically the pre-print (before printing) and/or post-print (the revised, evaluated and accepted) versions of their papers or works before their publication since this favors their circulation and early diffusion and therefore can help increase their citation and quotation, and also there reach through the academic community.
The works and papers that are published in this Journal are subject to the following terms:
1. The Publication Service of the University of Murcia (the publisher) has the Publication Rights (Copyright) to the published papers and works, and favors and permits the reusing of the same under the license indicated in point 2.
© Servicio de Publicaciones, Universidad de Murcia, 2013
2. The papers and works are to be published in the digital edition of the Journal under the license Creative Commons Reconocimiento-No Comercial-Sin Obra Derivada 3.0 España (legal text). The copying, using, spreading, transmitting and publicly displaying of the papers, works or publication are permitted as long as: i) the authors and original sources (Journal, publisher and URL of the publication) are quoted; ii) it is not used for commercial benefit; iii) the existence and specifications of this users license are mentioned.
3. Conditions of Self-Archiving. It is permitted and encouraged that the authors spread electronically the pre-print (before printing) and/or post-print (the revised, evaluated and accepted) versions of their papers or works before their publication since this favors their circulation and early diffusion and therefore can help increase their citation and quotation, and also there reach through the academic community.















