Changes in the estimated glucose disposal rate and cardiometabolic multimorbidity in middle-aged and older adults

Insulin resistance has been widely recognized as an independent risk factor for cardiovascular diseases and diabetes. The estimated glucose disposal rate (eGDR) is a well-established surrogate marker of insulin sensitivity; however, limited evidence exists regarding the dynamic changes of eGDR and their association with cardiometabolic multimorbidity. This study aimed to evaluate the associations of cumulative eGDR and eGDR change with the risk of cardiometabolic multimorbidity in middle-aged and older adults. This prospective cohort study included 4059 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were free of cardiovascular disease and diabetes at baseline. Groups of eGDR change were identified using K-means clustering method based on eGDR values at two time points. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cardiometabolic multimorbidity. During a median follow-up of 9.0 years, 843 (20.8%) participants developed cardiometabolic multimorbidity. Compared with the highest quartile of cumulative eGDR, the lowest quartile was significantly associated with a 1.67-fold increased risk of cardiometabolic multimorbidity (HR: 1.67; 95% CI 1.34–2.08; P < 0.001) after adjusting for potential confounders. Four distinct eGDR change groups were identified: consistent high, consistent moderate, consistent low, and moderate-low. Compared with the consistent high group, the moderate-low group showed the highest risk of cardiometabolic multimorbidity (HR: 1.64; 95% CI 1.30–2.06; P < 0.001), followed by consistent low group (HR: 1.62; 95% CI 1.32–1.99; P < 0.001) and consistent moderate group (HR: 1.26; 95% CI 1.04–1.53; P = 0.017). Cumulative eGDR and eGDR change were independently associated with increased risk of cardiometabolic multimorbidity in middle-aged and older adults. These findings highlight the importance of monitoring longitudinal eGDR change for early identification of individuals at high risk of cardiometabolic multimorbidity.