# Associations of Estimated Glucose Disposal Rate With Stroke Risk and Poststroke Adverse Outcomes: A Prospective Cohort Study

## TL;DR

Higher glucose disposal rates are linked to lower stroke risk and better post-stroke outcomes, suggesting improved insulin sensitivity could help prevent or treat strokes.

## Contribution

This study is the first to show that higher eGDR reduces stroke risk and poststroke complications, partially mediated by inflammation.

## Key findings

- Higher eGDR was associated with a 47% lower risk of stroke, especially ischemic stroke.
- Improved eGDR was linked to reduced poststroke adverse outcomes like depression and disability.
- Inflammatory markers partially explain the protective effect of higher eGDR on stroke risk.

## Abstract

This study investigated the relationship between estimated glucose disposal rate (eGDR), a validated marker of insulin resistance, and stroke subtypes and poststroke outcomes. Despite eGDR's established role in predicting cardiovascular outcomes, its impact on stroke risk and prognosis has not been fully explored.

This study included 462,550 participants from the UK Biobank with eGDR assessments, and participants were stratified into three categories based on tertiles of eGDR. The primary outcomes were stroke and its subtypes (ischemic and hemorrhagic stroke). Cox proportional hazard models and restricted cubic spline regression were used to analyze associations between eGDR and outcomes. Secondary analyses investigated poststroke adverse events (depression, disability, epilepsy, and delirium). Mediation analyses were conducted to explore the underlying mechanisms driven by inflammatory markers, eGDR, and stroke.

During a median follow‐up of 13.9 years, 12,325 stroke cases were recorded. Compared to the lowest eGDR tertile (< 6.525 mg/kg/min), individuals in the highest tertile (> 8.494 mg/kg/min) demonstrated a significantly reduced risk of stroke (HR = 0.53, 95% CI: 0.50–0.56), particularly ischemic stroke (HR = 0.53, 95% CI: 0.50–0.57). Higher eGDR levels were also associated with a decreased risk of poststroke adverse outcomes (HR = 0.83, 95% CI: 0.73–0.94), with similar risk estimates observed for depression, disability, epilepsy, and delirium. Furthermore, inflammatory markers partially mediated the relationship between eGDR and stroke risk.

Elevated eGDR levels were associated with decreased risks of stroke and poststroke adverse outcomes. These findings suggest improving insulin sensitivity, as reflected by higher eGDR, maybe a potential therapeutic target for stroke prevention or stroke rehabilitation.

Leveraging UK Biobank data, this study investigated the associations between estimated glucose disposal rate (eGDR), an insulin resistance marker, and stroke outcomes. Analyses revealed longitudinal and nonlinear relationships between eGDR and stroke subtypes, poststroke complications, and identified inflammatory markers as mediators of eGDR's effect on stroke risk.