The various associations between whole /regional fat mass and trajectory of cardiometabolic diseases: a nonlinear multistate model

Objective: This study aimed to investigate the association of whole body/regional fat mass (FM) with cardiometabolic disease (CMD) trajectory. Methods: We conducted a prospective analysis using the UK Biobank. The FM index (FMI), a surrogate for whole body FM, and regional FM (i.e., arm, leg, and trunk) were examined as exposures. A nonlinear multistate framework was used to evaluate the association between whole/regional FM and CMD trajectory. Results: Among the 423,966 participants (mean age 56.1 [SD 8.10] years, 43.9% men) with a median follow-up of 13.5 years, varied associations were identified between whole/regional FM and transitions in the CMD trajectory. Upper body FM (i.e., arm and trunk) exhibited significant positive J-shaped associations in the transitions from first CMD (FCMD) or cardiometabolic multimorbidity to death; however, FMI and leg FM demonstrated L-shaped associations. Leg FM played a beneficial role in the transition from FCMD to death, with a hazard ratio of 0.950 (95% CI: 0.931–0.968) per 1 kg. Conclusions: Body fat composition and distribution revealed various associations with CMD trajectory, highlighting their clinical importance. Upper body FM among those participants with FCMD or cardiometabolic multimorbidity demonstrated positive J-shaped associations toward death, providing no evidence of the “obesity paradox.”.