The association between long-term trajectories of insulin resistance and brain structural integrity in middle-aged and older adults

Background The triglyceride-glucose (TyG) index is considered a robust surrogate for insulin resistance (IR). The relationship between the trajectory patterns of the TyG index and subsequent brain structure changes is still unclear. Objective This study investigates the relationship between 10-year trajectories of TyG-related indices and brain structural integrity in a 10-year follow-up. Methods This prospective study included 898 participants (mean age 55.6 years, 34.4% males) from the community-based Shunyi Study. IR was assessed using the TyG index, TyG-body mass index (BMI) index, TyG-waist circumference index, and TyG-waist-to-height ratio (WHtR) index. The group-based trajectory model was employed to identify the 10-year trajectories. Structural brain measurements included structural changes of the whiter matter (white matter hyperintensities (WMHs), fractional anisotropy, and mean diffusivity) and gray matter (brain parenchymal fraction (BPF), cortical thickness, and hippocampal volume). General linear models were utilized to examine the association between the trajectory patterns of TyG-related indices and brain structure. Results Three distinct trajectories of TyG-related indices were identified from 2013 to 2023. The high-level trajectory groups of TyG-related indices exhibited a greater volume of WMHs and were more susceptible to disruptions in white matter microstructural integrity. This association was most significant for the TyG-BMI and TyG-WHtR trajectory groups. No significant correlations were found for BPF and cortical thickness among the different TyG-related indices trajectories. Conclusions The findings suggest that long-term IR primarily damages brain white matter rather than causing structural changes in gray matter.