Effect of Life Course Adiposity on Bell’s Palsy Mediated by Glucose Levels

Introduction and aims
Previous observational studies have reported an association between obesity and Bell’s palsy (BP), but the causality and the underlying mediating pathways remain unclear. We aimed to investigate the causal effects of adiposity across the life course on BP and to identify potential mediators in this relationship.
Methods
Utilizing summary statistics from genome-wide association studies predominantly of European ancestry, we conducted univariable and multivariable Mendelian randomization (MR) to estimate overall and independent effects of 5 adiposity-related traits (birth weight, childhood body mass index [BMI], adult BMI, adult body fat percentage, and adult waist circumference) on BP. Two-step MR was employed to assess the mediating role of metabolic and inflammatory traits. Sensitivity analyses were performed to evaluate robustness.
Results
Univariable MR revealed that genetically predicted adult BMI (OR: 1.29, 95% CI: 1.11-1.49, P = .001), body fat percentage (OR: 1.33, 95% CI: 1.08-1.65, P = .008), and waist circumference (OR: 1.29, 95% CI: 1.08-1.55, P = .005) were significantly associated with increased risk of BP. Multivariable MR confirmed an independent causal effect of adult BMI after adjusting for birth weight and childhood BMI. Two-step MR further identified glucose levels as a partial mediator, accounting for 23.8% (95% CI: 4.9%-42.6%) of the total effect. Findings were consistent across sensitivity analyses.
Conclusion
Higher genetically predicted adult BMI could increase the risk of BP, partly mediated by impaired glucose regulation.