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. 2024 Jun 18:15:1406793.
doi: 10.3389/fendo.2024.1406793. eCollection 2024.

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis

Wei Wang  1 , Xiu Li Guo  1 , Xiu Ping Qiu  1 , Yun Jie Yu  2 , Mei Tu  1
Affiliations

Systemic immune-inflammation index mediates the association between metabolic dysfunction-associated fatty liver disease and sub-clinical carotid atherosclerosis: a mediation analysis

Wei Wang et al. Front Endocrinol (Lausanne). .

Abstract

Background: Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM).

Method: This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS.

Results: The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%.

Conclusion: SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

Keywords: carotid intima-media thickness; hepatic steatosis; metabolic dysfunction-associated fatty liver disease; sub-clinical carotid atherosclerosis; systemic immune-inflammation index.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Spearman correlation analysis for the association among SII, cIMT, and CTL-S. SII, Systemic immune-inflammation index; cIMT, Carotid intima-media thickness; CTL-S, CT liver-spleen attenuation measurement.
Figure 2
Figure 2
Restricted cubic spines analysis for the correlation between Ln (SII) and MAFLD risk (A), as well as SCAS risk (B) after adjusting for Model 3. SII, Systemic immune-inflammation index; MAFLD, Metabolic dysfunction-associated fatty liver disease; SCAS, Subclinical carotid atherosclerosis. Model 3: adjusted for age, gender, diabetic duration, smoking, drinking, systolic blood pressure, diastolic blood pressure, waist circumference, body mass index, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, homeostatic model assessment of insulin resistance, alanine aminotransferase, and aspartate aminotransferase.
Figure 3
Figure 3
Structural model for the mediating role of SII (A) and Ln (SII) (B) in the association between MAFLD and SCAS after adjusting for Model 3. SII, Systemic immune-inflammation index; MAFLD, Metabolic dysfunction-associated fatty liver disease; SCAS, Subclinical carotid atherosclerosis. Model 3: adjusted for age, gender, diabetic duration, smoking, drinking, systolic blood pressure, diastolic blood pressure, waist circumference, body mass index, glycated hemoglobin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, uric acid, homeostatic model assessment of insulin resistance, alanine aminotransferase, and aspartate aminotransferase.
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The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.