Peripheral inflammation mediates the association between triglyceride-glucose index and cognitive impairment in comorbid major depressive disorder and type 2 diabetes: Translational implications for Alzheimer's disease risk via neuroinflammatory pathways.
Comorbid major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) are associated with accelerated cognitive impairment, potentially involving shared immunometabolic and inflammatory mechanisms. The triglyceride-glucose (TyG) index, a surrogate of insulin resistance, has been linked to inflammation. This study examined whether peripheral inflammation statistically mediates the association between TyG and cognitive impairment in patients with comorbid MDD and T2DM.
In this cross-sectional study, 256 patients with MDD and T2DM were enrolled. Cognitive impairment was defined as MoCA <26. Peripheral inflammatory markers (CRP, IL-6, TNF-α) and plasma Alzheimer's disease-related biomarkers (Aβ42/40 ratio, p-tau217) were measured. Multivariable logistic regression and mediation analyses were conducted with adjustment for relevant covariates.
Cognitive impairment was present in 59.37% of participants. Patients with impairment had higher TyG and inflammatory markers (all P < 0.001). TyG was independently associated with cognitive impairment (OR = 2.87, 95% CI: 1.68-4.91). TyG correlated with CRP, IL-6, and TNF-α (r = 0.35-0.42). Peripheral inflammation statistically mediated 28.41% of the TyG-cognition association. Impaired patients showed lower Aβ42/40 and higher p-tau217 (P < 0.001). Serial mediation suggested an indirect association via inflammation and p-tau217 (β = 0.10, 95% CI: 0.03-0.22), accounting for 12% of the total association.
Higher TyG index was statistically associated with cognitive impairment in comorbid MDD and T2DM, partly mediated by peripheral inflammation. While these cross-sectional findings highlight the potential of TyG as an accessible biomarker, longitudinal studies are needed to establish causality and directionality.
In this cross-sectional study, 256 patients with MDD and T2DM were enrolled. Cognitive impairment was defined as MoCA <26. Peripheral inflammatory markers (CRP, IL-6, TNF-α) and plasma Alzheimer's disease-related biomarkers (Aβ42/40 ratio, p-tau217) were measured. Multivariable logistic regression and mediation analyses were conducted with adjustment for relevant covariates.
Cognitive impairment was present in 59.37% of participants. Patients with impairment had higher TyG and inflammatory markers (all P < 0.001). TyG was independently associated with cognitive impairment (OR = 2.87, 95% CI: 1.68-4.91). TyG correlated with CRP, IL-6, and TNF-α (r = 0.35-0.42). Peripheral inflammation statistically mediated 28.41% of the TyG-cognition association. Impaired patients showed lower Aβ42/40 and higher p-tau217 (P < 0.001). Serial mediation suggested an indirect association via inflammation and p-tau217 (β = 0.10, 95% CI: 0.03-0.22), accounting for 12% of the total association.
Higher TyG index was statistically associated with cognitive impairment in comorbid MDD and T2DM, partly mediated by peripheral inflammation. While these cross-sectional findings highlight the potential of TyG as an accessible biomarker, longitudinal studies are needed to establish causality and directionality.
Authors
Yuan Yuan, He He, Elhassan Elhassan, Yu Yu, Lu Lu, Fang Fang, Zhu Zhu, Wu Wu, He He, Gu Gu
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