Abstract
<title>Abstract</title> <p>Background The association between the uric acid to high-density lipoprotein cholesterol ratio (UHR) and type 2 diabetes mellitus (T2DM) remains controversial, and most previous studies have focused on linear relationships. This study aimed to investigate the dose-response relationship between UHR and incident T2DM in a large nationwide cohort of middle-aged and older Chinese adults. Methods A total of 8,880 participants aged ≥ 45 years without baseline diabetes from the China Health and Retirement Longitudinal Study (CHARLS) were included. UHR was calculated as serum uric acid divided by HDL cholesterol. The primary outcome was incident T2DM during follow-up. Fine-Gray competing risk models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline (RCS) analysis was performed to explore potential nonlinear relationships. Subgroup and sensitivity analyses were conducted to assess the robustness of the results. Results During a median follow-up of 9 years, 1,206 incident T2DM cases were documented. There was no significant linear association between UHR and T2DM risk (HR per 1-standard deviation increase: 1.04, 95%CI: 0.96–1.12, P = 0.348). However, RCS analysis revealed a significant J-shaped nonlinear relationship (P for nonlinearity = 0.006). Compared with the lowest quartile of UHR, the highest quartile was associated with a 33% increased risk of T2DM (HR = 1.33, 95%CI: 1.08–1.62, P = 0.006). The 10-year absolute risk difference between the highest and lowest quartiles was 12.9%, and the population attributable fraction was 7.6%. Subgroup analyses showed consistent associations across sex, age, and BMI groups (all P-values for interaction > 0.05). Sensitivity analyses yielded similar results. Conclusions UHR is associated with incident T2DM in a J-shaped nonlinear manner among middle-aged and older Chinese adults. Only individuals with high UHR levels (≥ 75th percentile, ≥ 0.115) have a significantly increased risk of T2DM. These findings suggest that UHR may serve as a useful risk marker for identifying individuals at high risk of T2DM in clinical practice.</p>