Abstract
BACKGROUND AND OBJECTIVES: Estimated glucose disposal rate (eGDR) is a novel and reliable marker of insulin resistance (IR), yet its association with white matter hyperintensities (WMH) remains unclear. This study investigates the relationship between eGDR and WMH in a cohort from the UK Biobank. METHODS: We included 34,789 participants without a history of stroke or dementia at baseline. WMH volume was estimated from T2-FLAIR brain magnetic resonance imaging (MRI) scans acquired in 2014, normalized to intracranial volume, and log-transformed. Multiple linear regression models were used to examine the association between eGDR and WMH volume. Additionally, restricted cubic spline (RCS) analysis was employed to explore the dose-response relationship between eGDR and WMH volume. RESULTS: Each 1-SD increase in eGDR was significantly associated with a reduction in WMH volume (β = -0.057; 95% CI: -0.062 to -0.051; p < 0.001). Compared to participants in the lowest eGDR quartile (Q1), those in quartiles Q2, Q3, and Q4 exhibited progressively lower WMH volumes, with β coefficients of -0.068 (95% CI: -0.097 to -0.039), -0.199 (95% CI: -0.228 to -0.169), and -0.295 (95% CI: -0.330 to -0.259), respectively (p for trend < 0.001). RCS analysis demonstrated a significant linear inverse relationship between eGDR and WMH volume (p for nonlinearity > 0.05). Subgroup analyses indicated consistent associations across most predefined groups. CONCLUSION: Lower eGDR levels are associated with a greater burden of WMH, suggesting that eGDR may serve as a potential marker for predicting WMH burden in future clinical practice.