Changes in the Estimated Glucose Disposal Rate and Incident Cardiovascular Disease in Patients with Cardiovascular–Kidney–Metabolic Syndrome Stages 0–3: A Prospective Cohort Study in China

Background and aims Cardiovascular–kidney–metabolic syndrome (CKM) significantly increases the burden of cardiovascular disease (CVD), particularly in China,which has a rapidly aging population.The estimated glucose disposal rate (eGDR) is a reliable indicator for assessing insulin resistance (IR),but its dynamic changes and association with the risk of new-onset CVD in patients with CKM syndrome have not been fully elucidated.The aim of this study was to investigate the associations between dynamic changes in and cumulative of eGDR (cumeGDR) and the risk of new-onset CVD in Chinese adults with CKM syndrome. Methods ： A total of 2862 patients with CKM syndrome (stages 0–3) without CVD at baseline from the China Health and Retirement Longitudinal Study (CHARLS) were enrolled. K-means clustering was used to measure the change in eGDR from 2012 to 2015, and the cumulative eGDR level was calculated. Logistic regression, restricted cubic splines (RCS), and subgroup analysis were used to explore the potential associations between changes in the eGDR and the risk of new-onset CVD (including heart disease and stroke) in patients with CKM syndrome stages 0–3. Results ： During the 3-year follow-up period, 404 (14.1%) CVD events occurred, including 254 heart disease cases and 177 stroke cases. After adjusting for confounding factors, compared with the group with persistently high eGDR level (Class 1), the groups with significantly decreased eGDR level (Class 2) and persistently low eGDR level (Class 3) had a significantly increased CVD risk (Class 2: OR = 1.82 [1.36–2.45],P<0.001;Class 3: OR = 1.90 [1.41–2.56],P<0.001). Further RCS regression analysis revealed a negative linear association between the cumulative eGDR and CVD risk(P for overall <0.001, nonlinear P=0.922). Conclusion ： Persistently low eGDR level are associated with an increased risk of new-onset CVD in those with CKM syndrome stages 0–3. Continuous dynamic monitoring of the eGDR may help identify high-risk individuals with CKM syndrome stages 0–3 and provide critical evidence for early intervention.