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Introduction <p>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.</p> Methods <p>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.</p> Results <p>Active women had lower sIL-6R (<i>p</i> = 0.01, η² = 0.15) and sgp130 (<i>p</i> = 0.01, η² = 0.17) levels compared to inactive peers, with no difference in IL-6 (<i>p</i> = 0.84). Lower sIL-6R and sgp130 correlated with better processing speed (<i>r</i> = 0.37, <i>p</i> = 0.01) and visuospatial function (<i>r</i> = 0.36, <i>p</i> = 0.01); these associations remained significant after adjustment (<i>r</i> = 0.35, <i>p</i> = 0.04). PA was also associated with lower cholesterol (<i>r</i> = -0.37, <i>p</i> = 0.01) and FBS (<i>r</i> = -0.30, <i>p</i> = 0.04) and higher cardiovascular fitness (<i>r</i> = 0.32, <i>p</i> = 0.03).</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月12日

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  • Zakieh Heidari,
  • Mahdieh Molanouri Shamsi,
  • Amin Kadkhodaei,
  • Mehrdad Behmanesh,
  • Shahnaz Shahrbanian,
  • Sara Soudi

摘要

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.