Prospective association of the triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio with anxiety risk in a community-based cohort: a UK Biobank study
BMJ Open, 2025
Ren H., Zhao T., Lv Z., Xie G., Sun H.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Objective
To investigate whether the triglyceride-glucose (TyG) index and the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, as clinical surrogates of insulin resistance, predict the risk of anxiety, and to examine the potential mediating role of plasma proteins.
Design
Prospective cohort study.
Setting
Community-based population cohort in the United Kingdom.
Participants
A total of 412 767 participants aged 40–69 years without anxiety at baseline and with available data on TyG index and TG/HDL-C ratio were included. Among them, 43 991 participants had proteomic data with 2923 unique plasma proteins measured.
Primary and secondary outcome measures
The primary outcome was the incidence of first-episode anxiety. The main exposures were TyG index and TG/HDL-C ratio. Mediation analysis was conducted to assess the contribution of plasma proteins.
Results
During a median follow-up of 13.8 years, 21 616 cases of first-episode anxiety were identified. Higher quintiles of TyG index and TG/HDL-C ratio were significantly associated with increased anxiety risk (p trend <0.001). Each one SD increase in TyG index and TG/HDL-C ratio was associated with an 8% and 9% higher risk of anxiety, respectively. Mediation analysis showed that 36 proteins jointly explained 64.0% and 74.9% of the associations of TyG index and TG/HDL-C ratio with anxiety, respectively, with asialoglycoprotein receptor 1 (ASGR1) and protease serine 8 (PRSS8) identified as key mediators.
Conclusions
Elevated baseline TyG index and TG/HDL-C ratio are associated with an increased risk of anxiety, and this association may be mediated by ASGR1 and PRSS8.