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

Abstract

Aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: delirium; depression; disability; epilepsy; estimated glucose disposal rate; stroke.

FIGURE 1

Flowchart of participants in the study.

FIGURE 2

Association between eGDR level and the risk of stroke outcomes. (A) The dose–response associations between eGDR and stroke, ischemic stroke, and hemorrhagic stroke incidence. (B) Cumulative incidence of stroke, ischemic stroke, and hemorrhagic stroke according to baseline eGDR tertiles. Note: Nonlinear associations between eGDR and stroke outcomes were identified. The associations were further analyzed using eGDR tertiles. The hazard ratios for stroke risk are presented by eGDR tertiles, with the 1st tertile (lowest eGDR) as reference. Models adjusted for age, sex, ethnicity, education, Townsend deprivation index (TDI), smoking status, alcohol intake status, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), sleep duration, metabolic syndrome (MetS), and healthy diet.

FIGURE 3

Mediation analysis of the relationship between eGDR and stroke through inflammatory markers. (A) Neutrophil; (B) WBC; (C) NLR; (D) LMR; (E) PLR; (F) SII. Note: Models adjusted for age, sex, ethnicity, education, Townsend deprivation index (TDI), smoking status, alcohol intake status, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), sleep duration, metabolic syndrome (MetS) and healthy diet. β_IE indicates the indirect effects. WBC, white blood cell; NLR, Neutrophil‐to‐lymphocyte ratio; LMR, lymphocytes‐to‐monocytes ratio; PLR, platelets‐to‐lymphocytes ratio; SII, systemic immune inflammation index.