Abstract
Diabetes has been associated with an elevated risk of Parkinson's disease (PD), yet the relationship between prediabetes (PreD) and the incidence of PD in the adult population remains unclear. Therefore, a systematic review and meta-analysis was conducted to evaluate if PreD is also associated with a higher risk of PD. We conducted comprehensive searches of the PubMed, Embase, and Web of Science databases to identify relevant observational studies with longitudinal follow-up. The random-effects model was employed to synthesize the data, mitigating the potential impact of study heterogeneity on the outcomes. Our analysis incorporated seven datasets from five cohort studies, encompassing 18,170,592 adult participants without a PD diagnosis at baseline. Among them, 2,432,148 (13.3%) had PreD. During the follow-up, a total of 46,682 patients were diagnosed with PD. The pooled results indicated that PreD was associated with an increased incidence of PD (risk ratio [RR] 1.09, 95% confidence interval [CI] 1.02 - 1.16; P = 0.02; I2 = 52%), after adjusting for potential confounding factors such as age, sex, body mass index (BMI), and smoking. Subsequent pilot subgroup analyses suggested that the association between PreD and PD might not be significantly influenced by the country of the study, its design, age or sex of the participants, definition of PreD, or the quality scores of the study (P for subgroup difference all > 0.05). In conclusion, adult population with PreD may have a mildly increased risk of developing PD compared to those with normoglycemia.