Abstract
BACKGROUND: Insulin resistance and central obesity are major risk factors for cardiometabolic diseases. The triglyceride-glucose index (TyG) and lipid accumulation product (LAP) are markers that independently predict cardiometabolic risk. However, their combined long-term trajectories and impact on cardiometabolic multimorbidity (CMM) development remain unclear. METHODS: This cohort study utilized data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which tracked 3467 participants at baseline. Dual-trajectory of TyG and LAP were identified using a group-based dual-trajectory model. Cox proportional hazards models were employed to assess the relationships between dual-trajectory groups and primary cardiometabolic outcomes, including first cardiometabolic disease (FCMD), CMM (two or more conditions such as type 2 diabetes, coronary heart disease, or stroke), and all-cause mortality. Multi-state models were performed to assess the associations of dual-trajectory with CMM development. RESULTS: The study included 3467 participants with a mean age of 25.08 years (SD = 3.59). Of these, 43.4% (n = 1505) were male, and 53.2% (n = 1561) were White. Three distinct dual-trajectory groups were identified: low-increasing (61.5%), high-amplitude fluctuation (7.6%), and high-increasing (30.9%). After multivariate adjustment, compared with the low-increasing group, the high-amplitude fluctuation group exhibited significantly higher risks for FCMD (hazard ratio [HR] 1.38, 95% confidence interval [CI]: 1.08-1.77), CMM (HR 2.63, 95% CI 1.21-5.71), and all-cause mortality (HR 2.16, 95% CI 1.30-3.56), as well as elevated risks for transitions from baseline to FCMD (HR 1.41, 95% CI 1.17-1.63), FCMD to CMM (HR 2.07, 95% CI 1.53-3.96), CMM to death (HR 2.87, 95% CI 1.19-7.62). The high-increasing group showed similar results. CONCLUSIONS: Elevated and fluctuating trajectories of TyG and LAP from early adulthood are associated with increased risks of CMM development in midlife.