The effect of longitudinal trajectories of triglyceride-glucose index on the incident metabolic dysfunction-associated steatotic liver disease

Abstract

Background: The triglyceride-glucose (TyG) index is a reliable marker of insulin resistance and has been linked to metabolic disorders. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, particularly among older adults. The association between long-term changes in TyG levels and the risk of incident MASLD remains unclear. This study aimed to investigate the relationship between TyG index trajectories and the development of MASLD in the elderly. Methods: We conducted a prospective cohort study involving 28,535 older adults who underwent annual health checkups from 2018 to 2021 with complete triglyceride and fasting blood glucose data. Group-based trajectory modeling was used to identify three distinct TyG trajectories: the low-stable, moderate-stable, and high-stable groups. MASLD incidence was assessed during follow-up visits in 2022 and 2023. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MASLD across the trajectory groups. To minimize confounding, sensitivity analyses were conducted by excluding participants with a baseline body mass index (BMI) > 28 kg/m2 and those using antihypertensive, antidiabetic, or lipid-lowering medications. Additionally, restricted cubic spline regression was applied to examine the dose-response relationship between baseline TyG index and MASLD risk. Results: A total of 28,535 participants was included, comprising 13,456 males (47.16%) and 15,079 females (52.84%). The incidence rates of MASLD were 7.10% in the low-stable group, 16.10% in the moderate-stable group, and 23.20% in the high-stable group, increasing significantly with rising TyG trajectories (P < 0.001). After adjusting for age, sex, blood pressure, BMI, and lipid profiles, Cox regression models showed that the moderate-stable and high-stable groups had significantly higher risks of MASLD compared to the low-stable group, with HRs of 1.847 (95% CI: 1.699–2.008) and 2.361 (95% CI: 2.116–2.634), respectively (P < 0.001). A nonlinear dose-response relationship was also observed, with a sharp increase in MASLD risk when TyG index exceeded 8.54. Conclusion: Consistently elevated TyG trajectories are associated with a significantly increased risk of incident MASLD, with the risk escalating progressively as TyG levels rise.