Body mass index, diabetes, and the risk of Parkinson's disease

Background: There are conflicting findings in the literature regarding the association of body mass index and incidence of PD. Objectives: This study aimed to investigate the association of body mass index with the risk of PD incidence while considering diabetes mellitus as a major confounding factor. Methods: We examined 6,800,601 individuals (aged ≥40 years) who were free of PD using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios for PD with adjustment for potential confounders. Stratified analyses by diabetes status were also performed. Results: A total of 33,443 individuals were diagnosed with PD during the follow-up period (7.3 years). An increased risk of PD incidence was observed in the underweight group versus the normal group (adjusted hazard ratio: 1.28; 95% confidence interval: 1.21–1.36), whereas a decreased risk of PD incidence was observed (adjusted hazard ratio: 0.88; 95% confidence interval: 0.88–0.93) in the obese group and (adjusted hazard ratio: 0.77; 95% confidence interval: 0.72–0.82) in the severely obese group. This association consistently persisted after stratification by diabetes mellitus status, with the steepest downward slope for PD risk present with increasing body mass index in patients with severe diabetes mellitus (i.e., long duration or complication). Conclusions: Being underweight and diabetes mellitus were associated with an increased risk of PD incidence, and effect of being underweight was more prominent in those with diabetes mellitus, with a dose-response relationship existing according to diabetes mellitus status. Further research is warranted to understand the clinical implications of the significant interaction between being underweight and diabetes mellitus status in the development of PD.