Abstract
The association between insulin resistance and increased risk of Parkinson's disease (PD) has rarely been investigated. Our study aimed to investigate the association between the triglyceride/high-density lipoprotein (TG/HDL) ratio (which represents insulin resistance), and the incidence risk of PD in the general population. This study was conducted using data from the National Health Insurance Service-Health Screening Cohort Database of South Korea (2002-2019). We enrolled 310,023 participants who had no previous PD history and who had undergone more than three repeated measurements for the TG/HDL cholesterol ratio. The diagnosis of PD was determined using the International Classification of Diseases, 10th Revision code G20, specific reimbursement codes for Rare Intractable Diseases of V124, and a history of anti-PD drug prescription. During a median of 9.64 years (interquartile range 8.72-10.53), 4,587 individuals (1.47%) had an incidence of PD. Considering the multivariable time-dependent Cox proportional hazard model with repeated measures of average TG/HDL cholesterol ratio, a per unit increase in TG/HDL cholesterol ratio significantly increased the risk of PD in the entire cohort (hazard ratio (HR), 1.010; 95% confidence interval (CI), 1.001-1.020). These repeated measures of the average TG/HDL cholesterol ratio were associated with the incidence risk of PD in a J-shaped pattern for the entire diabetes mellitus (DM) and non-DM cohorts in restricted cubic spline analysis. Compared to the lowest tertiles (T1), the highest tertiles (T3) were positively associated with the incidence risk of PD (HR: 1.149, 95% CI 1.065-1.239 in the entire cohort, p for trend < 0.001; HR: 1.175, 95% CI 1.075-1.285 in the non-DM cohort, p for trend < 0.001). In contrast, the lowest (T1) and highest tertiles (T3) were not associated with the incidence risk of PD in the DM cohort (HR: 1.128, 95% CI 0.909-1.348) in fully adjusted multivariable analysis. Our study provides information that TG/HDL ratio may be positively associated with PD incidence risk in a non-DM population in longitudinal setting of the general population.