---
title: "Triglyceride-Glucose (TyG) Index and Mortality in Non-Diabetic Fibrotic Lung Disease on Antifibrot"
id: "plos-one-1-association-between-triglyceride-glucose-index-and-all-cause-mortality-in-non"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-1-association-between-triglyceride-glucose-index-and-all-cause-mortality-in-non"
content_type: "clinical_feed_article"
specialty: "Pulmonology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706"
published_at: "2026-09-02T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Triglyceride-Glucose (TyG) Index and Mortality in Non-Diabetic Fibrotic Lung Disease on Antifibrot
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-1-association-between-triglyceride-glucose-index-and-all-cause-mortality-in-non
- **Specialty:** [Pulmonology](https://medichelpline.com/clinical-feed/pulmonology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706)
- **Published At:** 2026-09-02T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This retrospective cohort study evaluated the association between the **TyG index** (a surrogate marker of insulin resistance) and **all-cause mortality** in 144 non-diabetic patients with radiologically defined **fibrotic lung disease** who started antifibrotic therapy between 2015 and 2023. - Patients with documented diabetes, those receiving fenofibrate, or without triglyceride measurements were excluded to focus on metabolic variability within the non-diabetic range. - Baseline measures included pulmonary function tests (FVC%, FEV1%, DLCO%), 6-minute walk test distance, fasting glucose, triglycerides, and calculation of the TyG index (Ln[(TG × glucose)/2]). - Cohort characteristics: mean age 67.4 years, 31.9% female, 59.7% current smokers, median smoking 35 pack-years among smokers; 45.1% received pirfenidone and 54.9% received nintedanib. - Median follow-up was 33.8 months; 54 of 144 patients (37.5%) died during follow-up. - Mean TyG index was 8.78; median triglycerides 123 mg/dL and median glucose 100 mg/dL. Mean baseline PFTs: FVC% 74.2% and DLCO% 50.6%. - In multivariable Cox regression (adjusted for sex, smoking pack-years, COPD, and FVC%), the **TyG index** was not significantly associated with **all-cause mortality** (adjusted HR 0.80, 95% CI 0.40–1.60, p = 0.54). - Lower **FVC%** and greater cumulative smoking exposure were independently associated with mortality in the adjusted model. - No consistent association between TyG and baseline pulmonary function was observed; an exploratory weak inverse correlation with **DLCO** was reported but not robust. - Study limitations include retrospective design, selected tertiary-center cohort, exclusion of diabetic patients which reduced metabolic variability, absence of uniform adjudication of comorbidities, potential fasting-status uncertainty for labs, limited event count restricting multivariable model complexity, and limited statistical precision. - Authors conclude TyG was not significantly associated with mortality in this selected non-diabetic antifibrotic-treated cohort and recommend prospective studies in broader populations to clarify potential prognostic relevance.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosone%2Farticle%3Fid%3D10.1371%2Fjournal.pone.0357706) * * About * Browse * Publish * [](https://journals.plos.org/plosone/ "PLOS One") * Search [advanced search](https://journals.plos.org/plosone/search) * [Browse Topics](https://journals.plos.org/plosone/subjectAreaBrowse) Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click [here](https://github.com/PLOS/plos-thesaurus/blob/master/README.md "Link opens in new window"). [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706) [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706) * 0 [Save](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#savedHeader) * 0 [Citation](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#citedHeader) * 43 [View](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#viewedHeader) * 0 [Share](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706#discussedHeader) Open Access Peer-reviewed Research Article # Association between triglyceride-glucose index and all-cause mortality in non-diabetic patients with fibrotic lung disease receiving antifibrotic therapy: A retrospective cohort study * Aysegul Erinc , Roles Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Visualization, Writing – original draft, Writing – review & editing * E-mail: draysgul@hotmail.com Affiliation Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Health Sciences University, Department of Pulmonology, Istanbul, Turkey [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-8822-7944 ](https://orcid.org/0000-0001-8822-7944 "ORCID Registry") ⨯ * Ali Kirac, Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing – review & editing Affiliation Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Health Sciences University, Department of Pulmonology, Istanbul, Turkey ⨯ * Fatma Ezgi Altun Acar, Roles Data curation, Investigation, Validation, Visualization Affiliation Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Health Sciences University, Department of Pulmonology, Istanbul, Turkey ⨯ * Abdullah Cagri Onal, Roles Data curation, Investigation, Validation, Visualization Affiliation Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Health Sciences University, Department of Pulmonology, Istanbul, Turkey ⨯ * Erdogan Cetinkaya Roles Data curation Affiliation Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Health Sciences University, Department of Pulmonology, Istanbul, Turkey ⨯ # Association between triglyceride-glucose index and all-cause mortality in non-diabetic patients with fibrotic lung disease receiving antifibrotic therapy: A retrospective cohort study * Aysegul Erinc, * Ali Kirac, * Fatma Ezgi Altun Acar, * Abdullah Cagri Onal, * Erdogan Cetinkaya ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: September 2, 2026 * * [Article](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706) * [Authors](https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0357706) * [Metrics](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0357706) * [Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0357706) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pone.0357706) * [Abstract](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#abstract0) * [Introduction](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec005) * [Materials and methods](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec006) * [Results](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec014) * [Discussion](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec015) * [Conclusions](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec016) * [Supporting information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec017) * [Acknowledgments](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#ack) * [References](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#references) * [Reader Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0357706) * [Figures](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706) ## Abstract ### Introduction Fibrotic lung diseases are associated with significant morbidity and mortality, with a rising prevalence. Prognostic indicators for these diseases include thoracic computed tomography (CT) findings and pulmonary function test (PFT) measures. The triglyceride-glucose (TyG) index, a fasting triglyceride- and glucose-derived surrogate marker of insulin resistance, has been associated with several clinical outcomes; however, its relationship with pulmonary function and all-cause mortality within the non-diabetic range in patients with fibrotic lung disease remains inadequately studied. This study aimed to investigate the association between variability in the TyG index within the non-diabetic range, baseline pulmonary function measures, and all-cause mortality in patients with fibrotic lung disease receiving antifibrotic therapy. ### Methods This retrospective cohort study was conducted on 144 patients with fibrotic lung disease who received antifibrotic therapy between 1 January 2015 and 1 June 2023. Demographic data, comorbidities, smoking status, PFT measures, fasting glucose, triglyceride levels, and survival data were collected. The TyG index was calculated using the formula: Ln [(fasting triglycerides (mg/dL) × fasting glucose (mg/dL)) / 2]. Survival time was calculated from initiation of antifibrotic therapy to death from any cause or last clinical follow-up, with a median follow-up duration of 33.8 months. ### Results The mean age of the cohort was 67.4 years, and 31.9% of the patients were female. The mean TyG index was 8.78. During follow-up, 54 of 144 patients (37.5%) died. In the multivariable Cox regression analysis, the TyG index was not significantly associated with all-cause mortality (adjusted HR = 0.80, 95% CI: 0.40–1.60, p = 0.54). Lower FVC% and greater cumulative smoking exposure were associated with all-cause mortality in the adjusted model. ### Conclusions In this selected cohort of non-diabetic patients with fibrotic lung disease receiving antifibrotic therapy, the TyG index was not significantly associated with all-cause mortality. No consistent association with baseline pulmonary function measures was observed, apart from a weak exploratory inverse correlation with DLCO. However, the restricted metabolic variability and limited statistical precision of the cohort may have reduced the ability to detect modest but potentially clinically meaningful associations. Further prospective studies are needed to clarify the potential prognostic relevance of the TyG index in broader fibrotic lung disease populations. ## Figures ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.g001) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.t002) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.g001) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.t002) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.g001) ![Table 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.t001) ![Table 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.t002) **Citation:** Erinc A, Kirac A, Altun Acar FE, Onal AC, Cetinkaya E (2026) Association between triglyceride-glucose index and all-cause mortality in non-diabetic patients with fibrotic lung disease receiving antifibrotic therapy: A retrospective cohort study. PLoS One 21(9): e0357706. https://doi.org/10.1371/journal.pone.0357706 **Editor:** Amir Hossein Behnoush, Northwestern University Feinberg School of Medicine, UNITED STATES OF AMERICA **Received:** December 5, 2025; **Accepted:** August 20, 2026; **Published:** September 2, 2026 **Copyright:** © 2026 Erinc et al. This is an open access article distributed under the terms of the [Creative Commons Attribution License](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Data Availability:** All relevant data are within the manuscript and its [Supporting Information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#sec017) files. **Funding:** The author(s) received no specific funding for this work. **Competing interests:** The authors have declared that no competing interests exist. ## Introduction Fibrotic lung diseases are parenchymal lung disorders characterized by high mortality and morbidity, with an increasing prevalence [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref001)]. The key prognostic indicators for these diseases include thoracic computed tomography imaging findings and pulmonary function test (PFT) measures [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref001)]. Recently, the role of metabolism in chronic lung diseases has become a prominent area of interest [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref002)]. The relationship between metabolic dysfunction, metabolic syndrome, and chronic lung disease has been increasingly explored [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref003)]. The triglyceride-glucose (TyG) index is calculated from fasting triglyceride and glucose concentrations and is widely used as a surrogate marker of insulin resistance. Although insulin resistance, diabetes mellitus, and metabolic syndrome are biologically related, they represent distinct clinical and pathophysiological constructs. The TyG index reflects the fasting triglyceride-glucose component of metabolic status and should not be interpreted as a measure of the entire metabolic syndrome phenotype [[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref004),[5](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref005)]. Although the TyG index has been associated with cardiovascular disease and the development of new-onset diabetes, its relationship with lung health remains inadequately studied [[6](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref006)–[8](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref008)]. Some studies have shown a cross-sectional association between the TyG index and respiratory symptoms, chronic bronchitis, and restrictive-type patterns of pulmonary dysfunction [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref003)]. It has also been reported that metabolic syndrome, IR, and systemic inflammation are important risk markers for reduced lung function in non-smoker healthy individuals [[9](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref009)]. Metabolic syndrome (MetS) is characterized by the clustering of central adiposity, dysglycemia or insulin resistance, hypertension, and atherogenic dyslipidemia and has been associated with chronic lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. Diabetes mellitus may coexist with MetS, but is not required for its diagnosis. Diabetes and hyperglycemia lead to a weakened immune response and increased susceptibility to infections, thus raising the risk of lung infections. Additionally, it has been suggested that increased parasympathetic signal changes associated with high insulin levels may trigger bronchial activity, creating a predisposition to subepithelial fibrosis [[10](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref010)–[13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref013)]. There are also experimental studies showing that disturbances in carbohydrate and lipid metabolism can lead to changes in surfactant composition [[14](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref014)]. Therefore, elevations in the TyG index may reflect metabolic disturbances related to dyslipidemia and impaired glucose metabolism, both of which have been associated with structural and functional lung changes in translational and experimental studies [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref003)]. However, the association of the TyG index with baseline pulmonary function and all-cause mortality has not been adequately investigated in patients with established fibrotic lung disease receiving antifibrotic therapy. Insulin resistance has been implicated in fibrotic processes through several proposed mechanisms, including insulin-like growth factor signaling, TGF-β activation, oxidative stress, and metabolic alterations in fibroblasts. On this basis, metabolic indices reflecting insulin resistance, such as the TyG index, have been proposed as potential markers of disease progression in chronic lung diseases [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref002),[15](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone.0357706.ref015)]. However, evidence regarding the relationship of these metabolic indices with longitudinal progression of fibrotic lung disease remains limited. Therefore, this study aimed to investigate the association between the TyG index, PFT measures, and survival in patients with fibrotic lung disease receiving antifibrotic therapy. Our objective was not to evaluate the effects of established diabetes mellitus, but rather to examine metabolic variability within a non-diabetic population using TyG index as a marker of subclinical insulin resistance. Accordingly, the findings should not be interpreted as reflecting the full spectrum of metabolic dysfunction in fibrotic lung disease populations. ## Materials and methods ### Study design and setting This retrospective cohort study was conducted at Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, a tertiary referral hospital specializing in respiratory diseases. The institution evaluates more than 200 patients with pulmonary fibrosis annually. Patients referred for evaluation of fibrotic lung disease undergo clinical assessment, pulmonary function testing, and high-resolution computed tomography. Decisions regarding the initiation of antifibrotic therapy are made through the institutional Interstitial Lung Diseases Council, consisting of pulmonology, occupational medicine, and radiology specialists. Although the individual council members may have changed during the 2015–2023 study period, antifibrotic treatment decisions were made within this institutional multidisciplinary framework throughout the study period. ### Ethics approval and informed consent statement This study was carried out in compliance with the Declaration of Helsinki. The Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital Ethics Committee approved the study protocol (ethical approval date, number: 13 July 2023, 2023−362). The requirement for written informed consent was waived due to the retrospective design. All extracted patient data were de-identified prior to statistical analysis. ### Study population This retrospective cohort study included adult patients (≥18 years) with fibrotic lung disease who received antifibrotic therapy at our center between 1 January 2015 and 1 June 2023. A total of 970 patients were initially screened for eligibility. Patients with a documented diagnosis of diabetes mellitus, those receiving fenofibrate therapy, and those without available triglyceride measurements were excluded to minimize pharmacological and disease-related influences on glucose and triglyceride levels and to allow evaluation of the TyG index as a marker of subclinical metabolic dysfunction within the non-diabetic range. After application of all predefined inclusion and exclusion criteria, 144 patients constituted the final analytic cohort. Fibrotic lung disease was defined based on radiological evidence of fibrosis on high-resolution computed tomography, including honeycombing, traction bronchiectasis or bronchiolectasis, and interlobular septal thickening. Interlobular septal thickening alone was not considered sufficient for inclusion and was required to be present as part of an overall radiologic pattern compatible with fibrotic lung disease. Because standardized retrospective classification into specific interstitial lung disease subtypes was not uniformly available, the study cohort represented a clinically heterogeneous group of fibrotic lung diseases rather than a single homogeneous diagnostic entity. The study flowchart is presented in [Fig 1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357706#pone-0357706-g001). [![thumbnail](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0357706.g001)](https://journals.plos.org/plosone/article/figure/image?size=medium&id=10.1371/journal.pone.0357706.g001 "Click for larger image") Download: * [PNG larger image](https://journals.plos.org/plosone/article/figure/image?download&size=large&id=10.1371/journal.pone.0357706.g001) * [TIFF original image](https://journals.plos.org/plosone/article/figure/image?download&size=original&id=10.1371/journal.pone.0357706.g001) Fig 1. Flowchart of the study population. [ https://doi.org/
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