Body mass index, metabolically abnormal status, and incident Parkinson's disease: Data from the UK Biobank

Abstract

Background The association between body mass index (BMI), metabolic conditions, and incident Parkinson's disease (PD) is quite complex. Objective To investigate the relationship between these variables, particularly the impact of metabolically healthy overweight/obese on the risk of PD, in the general population. Methods A total of 402,059 participants from the UK Biobank were categorized into four phenotypes according to the presence of overweight/obesity and/or metabolically abnormal status: overweight/obesity was defined as BMI >= 25 kg/m2; metabolically abnormal status was defined as having one or more metabolic risk factors including elevated blood pressure, fasting glucose, or triglyceride level, or reduced high-density lipoprotein cholesterol level. Cox proportional hazard regression analyses using four different models were performed to compare the risk of developing PD among the four BMI-metabolic status phenotypes. Results During the median follow-up of 13.5 years, 2283 (0.6%) patients were newly diagnosed with PD. Cox regression models demonstrated that individuals with overweight/obesity and those with metabolic abnormalities were at a higher risk of developing PD than their counterparts. Compared with the metabolically healthy non-overweight group (reference group), the two metabolically abnormal groups (either overweight/obese or non-overweight) showed a higher incidence of PD. The metabolically healthy overweight/obese group exhibited a comparable risk of developing PD to the metabolically healthy non-overweight group. Conclusions This study demonstrated that metabolically abnormal conditions are more relevant to incident PD than overweight/obesity. In particular, a metabolically healthy overweight/obese status does not increase the risk of developing PD compared with a metabolically healthy non-overweight status. Plain Language SummaryResearchers have long studied whether body weight and metabolic health affect the risk of developing Parkinson's disease,but results have been mixed. In particular, it was unclear whether people who are overweight but have good metabolichealth-known as"metabolically healthy overweight or obesity"-face a higher risk of Parkinson's disease. To explorethis, we analyzed data from over 400,000 people in the UK Biobank who did not have Parkinson's disease at the startof the study. We grouped participants into four categories based on whether they were overweight and whether theyhad metabolic problems such as high blood pressure, high blood sugar, or abnormal cholesterol levels. After followingthem for an average of 13.5 years, about 2300 people developed Parkinson's disease. We found that being overweightper se did not increase the risk of Parkinson's disease if metabolic health was normal. However, people with metabolic problems had a higher risk of developing Parkinson's disease regardless of their weight. These results suggest that poormetabolic health is more strongly linked to Parkinson's disease than body weight alone. Addressing metabolic issues earlymay help prevent or delay the onset of Parkinson's disease.