Cumulative exposure to the estimated glucose disposal rate and incident stroke in individuals with cardiovascular–kidney–metabolic syndrome stages 0–4: 6-year longitudinal evidence from CHARLS

BACKGROUND: The estimated glucose disposal rate (eGDR), an established measure of peripheral insulin sensitivity, contributes to stratifying the risk of cardio-cerebrovascular events. Nevertheless, the association between long-term eGDR exposure and stroke incidence throughout all stages (0-4) of cardiovascular-kidney-metabolic (CKM) syndrome remains unknown. METHODS: )/2* time (2015-2012). K-means clustering was used to analyse eGDR values from both 2012 and 2015 to identify distinct change patterns. To assess associations with stroke risk, we utilised multivariable logistic regression and restricted cubic spline models. RESULTS: During the 2015-2018 follow-up period, a total of 336 incident stroke cases were documented. Four distinct eGDR change patterns were identified. In fully adjusted models, compared with the participants in the persistent low pattern (Class 2), those in the moderate-high stable (OR 0.43, 95% CI: 0.31-0.58), stable high (OR 0.29, 0.19-0.43), and rapid decrease (OR 0.66, 0.47-0.91) patterns exhibited significantly lower stroke risk. Furthermore, each 1-unit increase in cumulative eGDR was associated with a 5% reduction in stroke odds (OR 0.95, 0.93-0.96). Restricted cubic spline analysis confirmed a linear inverse relationship between cumulative eGDR and stroke risk (P < 0.001; P for nonlinearity = 0.259). CONCLUSION: Cumulative eGDR is inversely associated with stroke risk across all CKM syndrome stages (0-4). This observation suggests that prolonged eGDR surveillance may be associated with improved risk stratification in this population.