---
title: "Triglyceride-Glucose Index, Peripheral Inflammation, and Cognitive Impairment in MDD with Type 2 D"
id: "pubmed-42025633"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42025633"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42025633/"
doi: "10.1016/j.jad.2026.121830"
published_at: "2026-08-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Triglyceride-Glucose Index, Peripheral Inflammation, and Cognitive Impairment in MDD with Type 2 D
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42025633
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42025633/)
- **DOI:** [10.1016/j.jad.2026.121830](https://doi.org/10.1016%2Fj.jad.2026.121830)
- **Published At:** 2026-08-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This cross-sectional study enrolled 256 patients with comorbid **major depressive disorder (MDD)** and **type 2 diabetes mellitus (T2DM)** to examine links among the triglyceride-glucose (TyG) index, peripheral inflammation, and cognitive impairment. - Cognitive impairment was defined by Montreal Cognitive Assessment (MoCA) score < 26; 59.37% of participants met this criterion. - Peripheral inflammatory markers measured were **CRP**, **IL-6**, and **TNF-α**; plasma Alzheimer's disease–related biomarkers measured were Aβ42/40 ratio and p-tau217. - Participants with cognitive impairment had higher TyG and higher levels of all measured inflammatory markers (P < 0.001). - TyG was independently associated with cognitive impairment after multivariable adjustment (OR 2.87, 95% CI 1.68–4.91). - TyG correlated with CRP, IL-6, and TNF-α (correlation coefficients r = 0.35–0.42), indicating a moderate positive relationship between TyG and peripheral inflammation. - Mediation analysis found that peripheral inflammation statistically mediated 28.41% of the association between TyG and cognitive impairment. - Impaired patients showed lower Aβ42/40 ratios and higher p-tau217 (P < 0.001); serial mediation analysis suggested an indirect TyG → inflammation → p-tau217 → cognition pathway (β = 0.10, 95% CI 0.03–0.22), accounting for 12% of the total association. - Authors highlight the potential of TyG as an accessible surrogate marker of insulin resistance linked to cognitive risk via inflammatory and AD-related biomarker pathways, but they caution that cross-sectional design precludes causal inference and call for longitudinal work. - Keywords and mechanistic context include **Alzheimer's disease risk**, **NLRP3 inflammasome**, **neuroinflammation**, and peripheral inflammatory signaling as translational implications.
## Clinical Analysis & Structured Key Points
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Epub 2026 Apr 21. # 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 [Qianfa Yuan](https://pubmed.ncbi.nlm.nih.gov/?term=Yuan+Q&cauthor_id=42025633)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-1 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: yqf1123@hotmail.com."), [Shen He](https://pubmed.ncbi.nlm.nih.gov/?term=He+S&cauthor_id=42025633)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-2 "Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China."), [Mohammed A M Elhassan](https://pubmed.ncbi.nlm.nih.gov/?term=Elhassan+MAM&cauthor_id=42025633)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-3 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China."), [Chunshui Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+C&cauthor_id=42025633)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-4 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China."), [Jing Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+J&cauthor_id=42025633)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-4 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China."), [Lingxiao Fang](https://pubmed.ncbi.nlm.nih.gov/?term=Fang+L&cauthor_id=42025633)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-4 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China."), [Xiaowei Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+X&cauthor_id=42025633)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-3 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China."), [Zheying Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+Z&cauthor_id=42025633)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-3 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China."), [Jue He](https://pubmed.ncbi.nlm.nih.gov/?term=He+J&cauthor_id=42025633)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-5 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. Electronic address: hejue2002@hotmail.com."), [Weijun Gu](https://pubmed.ncbi.nlm.nih.gov/?term=Gu+W&cauthor_id=42025633)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#full-view-affiliation-6 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: 13394050651@126.com.") Affiliations Expand ### Affiliations * 1 Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: yqf1123@hotmail.com. * 2 Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. * 3 Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. * 4 School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. * 5 School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. Electronic address: hejue2002@hotmail.com. * 6 Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: 13394050651@126.com. * PMID: **42025633** * DOI: [ 10.1016/j.jad.2026.121830 ](https://doi.org/10.1016/j.jad.2026.121830) Item in Clipboard # 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 Qianfa Yuan et al. J Affect Disord. 2026. Show details Display options Display options Format Abstract PubMed PMID J Affect Disord Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22J+Affect+Disord%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22J+Affect+Disord%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42025633/) . 2026 Aug 15:407:121830. doi: 10.1016/j.jad.2026.121830. Epub 2026 Apr 21. ### Authors [Qianfa Yuan](https://pubmed.ncbi.nlm.nih.gov/?term=Yuan+Q&cauthor_id=42025633)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-1 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: yqf1123@hotmail.com."), [Shen He](https://pubmed.ncbi.nlm.nih.gov/?term=He+S&cauthor_id=42025633)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-2 "Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China."), [Mohammed A M Elhassan](https://pubmed.ncbi.nlm.nih.gov/?term=Elhassan+MAM&cauthor_id=42025633)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-3 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China."), [Chunshui Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+C&cauthor_id=42025633)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-4 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China."), [Jing Lu](https://pubmed.ncbi.nlm.nih.gov/?term=Lu+J&cauthor_id=42025633)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-4 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China."), [Lingxiao Fang](https://pubmed.ncbi.nlm.nih.gov/?term=Fang+L&cauthor_id=42025633)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-4 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China."), [Xiaowei Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+X&cauthor_id=42025633)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-3 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China."), [Zheying Wu](https://pubmed.ncbi.nlm.nih.gov/?term=Wu+Z&cauthor_id=42025633)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-3 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China."), [Jue He](https://pubmed.ncbi.nlm.nih.gov/?term=He+J&cauthor_id=42025633)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-5 "School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. Electronic address: hejue2002@hotmail.com."), [Weijun Gu](https://pubmed.ncbi.nlm.nih.gov/?term=Gu+W&cauthor_id=42025633)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42025633/#short-view-affiliation-6 "Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: 13394050651@126.com.") ### Affiliations * 1 Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: yqf1123@hotmail.com. * 2 Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China. * 3 Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. * 4 School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. * 5 School of Mental Health and the Affiliated Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. Electronic address: hejue2002@hotmail.com. * 6 Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen XianYue Hospital, Xian Yue Hospital Affiliated with Xiamen Medical College, Xiamen, 361000, Fujian, China. Electronic address: 13394050651@126.com. * PMID: **42025633** * DOI: [ 10.1016/j.jad.2026.121830 ](https://doi.org/10.1016/j.jad.2026.121830) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Background:** 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. **Methods:** 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. **Results:** 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. **Conclusions:** 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. **Keywords:** Alzheimer's disease risk; NLRP3 inflammasome; Neuroinflammation; Peripheral inflammation; Triglyceride-glucose index. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. ## Similar articles * [ Exploring the relationship of triglyceride to high-density lipoprotein cholesterol and the triglyceride-glucose index with white matter hyperintensities in individuals with type 2 diabetes: a cross-sectional analysis. ](https://pubmed.ncbi.nlm.nih.gov/41377947/) Pan J, Zheng J, Dong H, Zhang H, Hu Z, Tang Z, Xu H.Pan J, et al.Front Endocrinol (Lausanne). 2025 Nov 25;16:1639083. doi: 10.3389/fendo.2025.1639083. eCollection 2025.Front Endocrinol (Lausanne). 2025.PMID: 41377947Free PMC article. * [ Association between triglyceride-glucose index and diabetic retinopathy among patients with diabetes mellitus in Nepalese patients: a cross-sectional study. ](https://pubmed.ncbi.nlm.nih.gov/41654809/) Thapa S, Ghimire A, Kunwar B, Aryal B, Adhika
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