Association of triglyceride–glucose frailty index with depressive symptom trajectories varies across cardiometabolic multimorbidity progression patterns

Metabolic dysfunction and frailty may be associated with depressive symptom burden in middle-aged and older adults, but the interplay with cardiometabolic multimorbidity (CMM) trajectories and sleep-related factors remains unclear. Using data from 5 waves of the China Health and Retirement Longitudinal Study (CHARLS), 5,870 participants were classified into depressive symptom trajectories using scores from the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). Associations between the triglyceride-glucose frailty index (TyGFI) and depressive symptom trajectory were analyzed. Stratified analyses by CMM trajectory subgroups and exploratory mediation analyses of sleep-related factors were performed. Among participants, 4,611 (78.6%) were in the low depressive symptoms trajectory and 1,259 (21.4%) in the high trajectory group. The high trajectory group had higher TyGFI, shorter sleep duration, and a higher proportion of women, rural residents, and participants without a spouse (all P < 0.001). A generalized additive model showed a nonlinear association between TyGFI and depressive symptom trajectory, and two-piecewise logistic regression identified an estimated change point at 49.76. Stratified analyses showed that higher TyGFI was associated with greater odds of belonging to the high depressive symptom trajectory across all CMM trajectory subgroups, with the strongest association in the healthy-to-cardiovascular disease progression group (H → C) and the weakest in the healthy-to-cardiovascular disease-to-cardiometabolic multimorbidity progression group (H → C → CMM) (P for interaction = 0.0106). Exploratory mediation analysis suggested that overall sleep quality statistically accounted for 16.9% of the observed association between TyGFI and depressive symptom trajectory membership (P < 0.001). Higher TyGFI was associated with greater odds of belonging to an unfavorable depressive symptom trajectory among middle-aged and older adults, and the strength of this association differed across CMM trajectories. Exploratory mediation analysis indicated that overall sleep quality statistically accounted for part of the observed association.