Background: Preserved Ratio Impaired Spirometry (PRISm) is a high-risk lung phenotype with elevated cardiovascular mortality, yet its underlying mechanisms are poorly defined. Systemic insulin resistance (IR) is a potential key driver, but comprehensive studies linking IR indices to PRISm are lacking.
Aims & Hypotheses: We aim to: 1) Investigate cross-sectional associations between multiple IR indices (TyG, TyG-BMI, TyG-WC, TyG-WHtR, TyG-ABSI, TG/HDL-C, HOMA-IR, METS-IR) and PRISm prevalence; 2) Examine if baseline IR predicts lung function trajectories (persistence, improvement, progression to COPD) in PRISm; 3) Assess the prognostic value of IR indices for cardiovascular mortality in PRISm. We hypothesize that higher IR levels are strongly associated with PRISm, its unfavorable progression, and increased cardiovascular risk.
Methods: We will conduct cross-sectional, longitudinal, and prospective cohort analyses in UK Biobank. Participants will be categorized by spirometry (Normal, PRISm, COPD). Multivariable logistic regression will assess Aim 1. Lung function trajectories will be modeled using multinomial regression for Aim 2. Cox proportional hazards models, complemented by C-index, NRI, and IDI analyses, will evaluate the prediction of cardiovascular mortality for Aim 3.
Required Data: Spirometry (FEV1, FVC), anthropometrics (BMI, WC), biomarkers (glucose, HbA1c, triglycerides, HDL-C, insulin, CRP), death registries, and hospital inpatient data.
Expected Outcomes & Impact: We expect IR indices, especially TyG-adiposity combinations, to be strongly linked to PRISm prevalence, progression, and cardiovascular mortality. This will establish IR as a key mechanism in PRISm and provide simple biomarkers for risk stratification, enabling targeted prevention.
Timetable: Months 1-3 a preparation; Months 4-16 Primary analysis; Months 17-22 Manuscript submission (Primary aims); Months 23-36: Secondary analysis and manuscript.
