Association of triglyceride glucose-waist to height ratio index with Parkinson’s disease and the mediating role of systemic inflammatory response index: A cross-sectional study

Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing global incidence, yet its pathogenesis remains unclear. Insulin resistance and central obesity may be linked to PD via inflammatory mechanisms. This study aims to investigate the association between triglyceride-glucose waist-to-height ratio (TyG-WHtR) index and PD risk and the mediating role of systemic inflammatory response index (SIRI). This cross-sectional study utilized data extracted from the National Health and Nutrition Examination Survey database (1999-2020). Multivariable logistic regression models were used to estimate odds ratios (ORs) for PD, with survey weights applied for complex sampling design. Stratified analyses were also conducted. Mediation analysis was performed to evaluate the role of SIRI. The PD group had higher age, waist circumference, and glucose levels but lower family income and physical activity. An unadjusted analysis revealed a 32% increased PD risk per 1-unit increase of TyG-WHtR (OR = 1.32, 95% CI = 1.18-1.49, P < .001). After adjusting for liver/kidney function, the association persisted (OR = 1.21, 95% CI = 1.004-1.46, P = .045). A 38.5% higher risk in adults aged 18-50 (OR = 1.39, P < .001). SIRI mediated 96.42% of the association (95% CI = 0.93-0.98, P < .001). TyG-WHtR index correlates with PD risk, predominantly mediated by SIRI. These findings support TyG-WHtR and SIRI as early risk markers for PD and highlight inflammatory pathways.