Association Between Stress Hyperglycemia Ratio and Parkinson's Disease Across Different Glucose Metabolism Statuses-A Prospective Study From UK Biobank.

BACKGROUND

The stress hyperglycemia ratio (SHR) has been linked to adverse outcomes in various conditions, yet its association with Parkinson's disease (PD) remains unclear. This study investigates the relationship between SHR and PD risk across sex and glucose metabolism statuses using data from the UK Biobank.

METHODS

In this prospective cohort study, 406,271 participants without baseline PD from the UK Biobank were included. SHR was calculated as [FPG (mmol/L)]/[1.59 × HbA1c (%)-2.59] and divided into tertiles. Incident PD cases were identified via linked medical records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with analyses stratified by sex and diabetes status (nondiabetic, prediabetic, diabetic).

RESULTS

Over a median follow-up of 9 years, 2837 PD cases were identified. In men, elevated SHR was associated with increased PD risk, with the highest tertile (T3) showing a significantly higher risk compared with the lowest (T1) (HR: 1.20, 95% CI: 1.06-1.37). This association was strongest in nondiabetic men (T3 vs. T1: HR: 1.25, 95% CI: 1.08-1.45). No significant associations were observed in women or in prediabetic or diabetic men, either across tertiles or as a continuous variable.

CONCLUSION

Elevated SHR is independently linked to an increased PD risk in men, particularly those without diabetes, but not in women or other glucose metabolism groups. These findings suggest a sex-specific role of acute metabolic stress in PD pathogenesis and emphasize the need to consider glucose metabolism status in PD risk assessment.