Metabolic score for insulin resistance and cancer mortality - Effect modification by hypertension in a nationwide cohort study

Sep 23, 2026

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Metabolic score for insulin resistance (METS-IR) links to cardiovascular mortality, while its relationship with cancer-specific mortality remains uncertain. This retrospective nationwide cohort study analyzed 17,347 adults from NHANES (1999–2018) with follow-up through December 31, 2019. METS-IR was computed from fasting glucose, triglycerides, and related indicators. Weighted Cox and additional analyses showed a dose–response association with cancer-specific mortality and persistence under categorical models. Hypertension significantly modified the METS-IR–cancer mortality association, supported by subgroup, stratified, and sensitivity analyses, with stronger effects in the US population.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Introduction

Study background and rationale

Methods

Cohort, exposure definition, and follow-up

Statistical analyses

Results

Association between METS-IR and cancer-specific mortality

Effect modification by hypertension

Robustness checks

Conclusions

® Observational Study Metabolic score for insulin resistance and cancer mortality Effect modification by hypertension in a nationwide cohort study Huanrong Wang, MMa , Hua Bai, MMa , Wenhui Wang, MMa , Dan Yang, MMa , Fanfan Zhou, MMa , Meifeng Yin, MMa , Kai Li, MMa , Yunxia Guo, MMb , Ruijun Li, MMa ,* | Abstract
The metabolic score for insulin resistance (METS-IR) is associated with cardiovascular mortality, but its association with cancerspecific mortality remains unclear. This retrospective cohort study included 17,347 adults from the National Health and Nutrition Examination Survey 1999 to 2018. METS-IR was calculated based on fasting glucose, triglycerides and other indicators, with follow-up until December 31, 2019. Weighted Cox models and other analyses were performed. The results showed that each 1-unit increase in METS-IR was associated with a 3% higher risk of cancer-specific mortality (P = .01), presenting an approximately linear dose–response relationship; METS-IR remained associated with cancer mortality risk when analyzed asa categorical variable. Subgroup analyses revealed a significant interaction between hypertension and METS-IR in relation to cancer mortality, and stratified analyses further indicated that hypertension status acted as an effect modifier of this association. Sensitivity analyses confirmed the robustness of these findings. Higher METS-IR was independently associated with increased risks of cancer mortality in the US population, with hypertension significantly amplifying this association. | | --- | | Abbreviations: BMI = body mass index, CI = confidence intervals, HDL-C = high-density lipoprotein cholesterol, HR = hazard ratios, MEC = mobile examination center, METS-IR = metabolic score for insulin resistance, NDI = National Death Index, NHANES = the National Health and Nutrition Examination Survey, PIR = poverty-income ratio, T2DM = type 2 diabetes mellitus. | | Keywords: cancer mortality, general population, hypertension, metabolic score for insulin resistance, NHANES | 1. Introduction Cancer remains one of the leading causes of morbidity and mortality worldwide. Despite substantial advances in cancer prevention, early detection, and therapeutic strategies, its global incidence continues to rise, and survival outcomes remain highly heterogeneous across populations and tumor types. [1,2] In the United States, gains in cancer survival have been partially offset by the growing burden of population aging, obesity, and metabolic dysfunction (factors that are now firmly established as major determinants of both cancer risk and prognosis) . [1,3] Among these, insulin resistance represents a central pathophysiological hallmark of metabolic dysfunction, mechanistically linking obesity and type 2 diabetes mellitus (T2DM) to a pro-tumorigenic milieu characterized by hyperinsulinemia, chronic low-grade inflammation, and dysregulation of insulin/ insulin-like growth factor signaling. This altered metabolic environment promotes cellular proliferation while inhibiting apoptosis, thereby facilitating tumor initiation and progression. [4–6] A substantial body of epidemiological evidence has demonstrated that metabolic syndrome, hyperinsulinemia, and T2DMare associated with increased incidence and poorer survival across multiple malignancies, including colorectal, pancreatic, hepatic, endometrial, and postmenopausal breast cancers. [1,5,6] However, This study was funded by the Henan Provincial Medical Science and Technology Innovation Program (Joint Construction Project) (No. LHGJ20250696). This study is a secondary analysis of de-identified public data from NHANES, for which written informed consent was obtained by the NCHS Ethics Review Committee from all participants at the time of data collection, and thus no additional informed consent was required for our analysis. The authors have no conflicts of interest to disclose. All data generated or analyzed during this study are i

FAQs

What is METS-IR and how is it used in this study?

METS-IR (metabolic score for insulin resistance) is calculated from fasting glucose, triglycerides, and other indicators. The study evaluates how METS-IR relates to cancer-specific mortality across the cohort.

What did the study find about METS-IR and cancer-specific mortality?

Each 1-unit increase in METS-IR was associated with a higher risk of cancer-specific mortality, showing an approximately linear dose–response relationship. The association remained when METS-IR was analyzed as a categorical variable.

How did hypertension influence the METS-IR–cancer mortality relationship?

Subgroup and stratified analyses showed a significant interaction between hypertension and METS-IR for cancer mortality. Hypertension status acted as an effect modifier, amplifying the association.

Sep 23, 2026

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