Association between four indirect indicators of insulin resistance and lung cancer - evidence from UK Biobank and Mendelian randomization analysis

Sep 22, 2026

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Insulin resistance (IR) is increasingly linked to cancer, but its relationship with lung cancer (LC) remains uncertain. This prospective UK Biobank study assessed four indirect IR indicators—TyG index, TyG-BMI, TG/HDL-C, and METS-IR—against LC risk. Using Cox regression, restricted cubic splines, and ROC-based discrimination, it found higher indicator levels corresponded to greater cumulative LC incidence, strongest for METS-IR; no clear associations for adenocarcinoma or squamous carcinoma. Mendelian randomization did not support causality, suggesting metabolic vulnerability.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Dang et al. BMC Cancer (2026) 26:393 BMC Cancer [https://doi.org/10.1186/s12885-026-15697-w](https://doi.org/10.1186/s12885-026-15697-w) RESEARCH Open Access Association between four indirect indicators of insulin resistance and lung cancer: evidence from UK biobank and Mendelian randomization analysis Yongze Dang1, Xia Li1, Yutong Cheng2, Shupei Pan1, Guoliang Li3, Xiaoxiao Liu1, Yuchen Wang1, Xinyu He 1, Shangyi Geng1, Hongbing Ma1*, Jingkun Qu4* and Xixi Zhao1* Abstract Background Insulin resistance (IR) has been increasingly linked to cancer development and progression, but its association with lung cancer (LC) remains unclear. This prospective study investigated the association between four indirect IR indicators—triglyceride-glucose (TyG) index, TyG combined with body mass index (TyG-BMI), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and metabolic score for IR (METS-IR), and LC risk. Methods A total of 388,013 participants without previous cancer at baseline from the UK Biobank were included. Cox hazards regression models were used to examine the associations between four indirect indicators of IR and LC. Restricted cubic splines (RCS) evaluated nonlinear associations. The discriminatory ability of each index was assessed using the area under the receiver operating characteristic (ROC) curve. Sensitivity analyses were performed to test robustness. In addition, Mendelian randomization (MR) analysis was performed to explore potential causal relationships. Results Among 388,013 cancer-free participants from UK Biobank, 3527 incident LC cases were documented during a median follow-up of 13.25 years. Kaplan-Meier analysis revealed associations between higher levels of four indicators and increased cumulative LC incidence. In fully adjusted Cox regression models, METS-IR exhibited the strongest association with overall LC, with the highest quartile associated with an increased risk (hazard ratio: 1. 24, 95% confidence interval: 1.05–1.47) . No statistically significant associations were observed for lung adenocarcinoma or lung squamous cell carcinoma. In contrast, several indicators remained associated with small cell lung cancer (SCLC), with elevated risks observed forTG/HDL-C (1 . 52, 1.03–2. 25), METS-IR (2 . 30, 1.29–4. 11), and TyG-BMI (2 . 22, 1.20– 4. 08) in the highest quartiles. RCS analyses suggested predominantly linear associations. ROC curve analyses indicated *Correspondence: Hongbing Ma[mhbxian@126.com](mhbxian@126.com)[ ](mhbxian@126.com)Jingkun Qu [qujingkun@xjtu.edu.cn](qujingkun@xjtu.edu.cn)[ ](qujingkun@xjtu.edu.cn)Xixi Zhao [xixizhao@xjtu.edu.cn](xixizhao@xjtu.edu.cn) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.) Dang et al. BMC Cancer (2026) 26:393 Page 2 of 13 modest discriminatory performance, with relativ

FAQs

Which four indirect indicators of insulin resistance were evaluated for lung cancer risk?

The study evaluated TyG index, TyG combined with BMI (TyG-BMI), TG/HDL-C, and METS-IR as indirect measures of insulin resistance.

What were the main findings about the association with overall lung cancer?

Higher levels of all four indicators were linked to increased cumulative lung cancer incidence, with METS-IR showing the strongest association in fully adjusted Cox models.

Did Mendelian randomization support a causal relationship between insulin resistance indicators and lung cancer?

No. Mendelian randomization analyses did not provide evidence supporting a causal association.

Sep 22, 2026

Uploaded by Rhys