Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators

Abstract Introduction Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, with dysregulation of the interleukin-6 (IL-6) signaling pathway—particularly its soluble receptors—implicated in both T2DM pathogenesis and cognitive dysfunction. The potential role of sIL-6R (soluble int...

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Main Authors: Zakieh Heidari, Mahdieh Molanouri Shamsi, Amin Kadkhodaei, Mehrdad Behmanesh, Shahnaz Shahrbanian, Sara Soudi
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Diabetology & Metabolic Syndrome
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Online Access:https://doi.org/10.1186/s13098-025-01908-0
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author Zakieh Heidari
Mahdieh Molanouri Shamsi
Amin Kadkhodaei
Mehrdad Behmanesh
Shahnaz Shahrbanian
Sara Soudi
author_facet Zakieh Heidari
Mahdieh Molanouri Shamsi
Amin Kadkhodaei
Mehrdad Behmanesh
Shahnaz Shahrbanian
Sara Soudi
author_sort Zakieh Heidari
collection DOAJ
description Abstract Introduction Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, with dysregulation of the interleukin-6 (IL-6) signaling pathway—particularly its soluble receptors—implicated in both T2DM pathogenesis and cognitive dysfunction. The potential role of sIL-6R (soluble interleukin-6 receptor) and sgp130 (soluble glycoprotein 130) as mediators in the relationship between physical activity (PA) and cognitive performance in women with T2DM remains underexplored. This study examined the associations between PA, sIL-6R, and sgp130 levels and their relationship with cognitive function in this population. Methods This cross-sectional observational analytical study was conducted on 44 women (aged 50–75 years) with T2DM. We evaluated PA levels; serum concentrations of sIL-6R, sgp130, and IL-6; domain-specific cognitive performance; physical fitness; and diabetes-related metabolic indicators. Correlations between PA, selected cytokines, and cognitive performance were analyzed using correlation analyses and adjusted ANCOVA. Results Active women had lower sIL-6R (p = 0.01, η² = 0.15) and sgp130 (p = 0.01, η² = 0.17) levels compared to inactive peers, with no difference in IL-6 (p = 0.84). Lower sIL-6R and sgp130 correlated with better processing speed (r = 0.37, p = 0.01) and visuospatial function (r = 0.36, p = 0.01); these associations remained significant after adjustment (r = 0.35, p = 0.04). PA was also associated with lower cholesterol (r = -0.37, p = 0.01) and FBS (r = -0.30, p = 0.04) and higher cardiovascular fitness (r = 0.32, p = 0.03). Conclusion Regular PA in women with T2DM is associated with reduced sIL-6R and sgp130 levels, which may be linked to better cognitive performance across multiple domains. These findings highlight the potential role of sIL-6R and sgp130 in linking PA to cognitive health, underscoring the importance of PA as a supportive strategy for managing inflammation and mitigating cognitive decline in T2DM.
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spelling doaj-art-2e757345160e45f1807e7e03335f86bc2025-08-20T03:05:07ZengBMCDiabetology & Metabolic Syndrome1758-59962025-08-0117111210.1186/s13098-025-01908-0Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediatorsZakieh Heidari0Mahdieh Molanouri Shamsi1Amin Kadkhodaei2Mehrdad Behmanesh3Shahnaz Shahrbanian4Sara Soudi5Department of Physical Education & Sport Sciences, Faculty of Humanities, Tarbiat Modares UniversityDepartment of Physical Education & Sport Sciences, Yazd University, SafaeihDepartment of Physical Education & Sport Sciences, Faculty of Humanities, Tarbiat Modares UniversityDepartment of Genetics, School of Biological Sciences, Tarbiat Modares UniversityDepartment of Physical Education & Sport Sciences, Faculty of Humanities, Tarbiat Modares UniversityDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Jala Ale Ahmad Exp. TehranAbstract Introduction Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, with dysregulation of the interleukin-6 (IL-6) signaling pathway—particularly its soluble receptors—implicated in both T2DM pathogenesis and cognitive dysfunction. The potential role of sIL-6R (soluble interleukin-6 receptor) and sgp130 (soluble glycoprotein 130) as mediators in the relationship between physical activity (PA) and cognitive performance in women with T2DM remains underexplored. This study examined the associations between PA, sIL-6R, and sgp130 levels and their relationship with cognitive function in this population. Methods This cross-sectional observational analytical study was conducted on 44 women (aged 50–75 years) with T2DM. We evaluated PA levels; serum concentrations of sIL-6R, sgp130, and IL-6; domain-specific cognitive performance; physical fitness; and diabetes-related metabolic indicators. Correlations between PA, selected cytokines, and cognitive performance were analyzed using correlation analyses and adjusted ANCOVA. Results Active women had lower sIL-6R (p = 0.01, η² = 0.15) and sgp130 (p = 0.01, η² = 0.17) levels compared to inactive peers, with no difference in IL-6 (p = 0.84). Lower sIL-6R and sgp130 correlated with better processing speed (r = 0.37, p = 0.01) and visuospatial function (r = 0.36, p = 0.01); these associations remained significant after adjustment (r = 0.35, p = 0.04). PA was also associated with lower cholesterol (r = -0.37, p = 0.01) and FBS (r = -0.30, p = 0.04) and higher cardiovascular fitness (r = 0.32, p = 0.03). Conclusion Regular PA in women with T2DM is associated with reduced sIL-6R and sgp130 levels, which may be linked to better cognitive performance across multiple domains. These findings highlight the potential role of sIL-6R and sgp130 in linking PA to cognitive health, underscoring the importance of PA as a supportive strategy for managing inflammation and mitigating cognitive decline in T2DM.https://doi.org/10.1186/s13098-025-01908-0Type 2 diabetes mellitusCognitive functionPhysical activityMetabolic healthIL-6sIL-6R
spellingShingle Zakieh Heidari
Mahdieh Molanouri Shamsi
Amin Kadkhodaei
Mehrdad Behmanesh
Shahnaz Shahrbanian
Sara Soudi
Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators
Diabetology & Metabolic Syndrome
Type 2 diabetes mellitus
Cognitive function
Physical activity
Metabolic health
IL-6
sIL-6R
title Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators
title_full Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators
title_fullStr Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators
title_full_unstemmed Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators
title_short Interplay between physical activity, inflammation, and cognitive performance in women with type 2 diabetes: an observational study focused on IL-6 pathway mediators
title_sort interplay between physical activity inflammation and cognitive performance in women with type 2 diabetes an observational study focused on il 6 pathway mediators
topic Type 2 diabetes mellitus
Cognitive function
Physical activity
Metabolic health
IL-6
sIL-6R
url https://doi.org/10.1186/s13098-025-01908-0
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