Prediabetes, type 2 diabetes mellitus and risk of Parkinson's disease: A population-based cohort study.

Abstract Background Association of type 2 diabetes mellitus (T2D) with subsequent Parkinson's disease (PD) has supported the link between glucose metabolism and PD. We assessed the risk of PD not only in T2D but also in prediabetes. Methods We conducted a retrospective cohort study of the population attended in primary care centres of the Catalan Health Institute in Catalonia between 2006 and 2018. The data were obtained from the Information System for Research in Primary Care (SIDIAP). We created a cohort of T2D and prediabetes patients (HbA1c ≥ 5.7–6.4% without antidiabetic drugs or previous T2D diagnosis) and compared to a reference cohort. The outcome was PD diagnosis and we excluded PD before or during the first year of follow-up. We used multivariate Cox regression models to calculate hazard ratios (HR) and 95% confidence intervals (95%CI). We excluded subjects with atypical and secondary parkinsonisms. Results The exposed cohorts comprised of 281.153 patients with T2D and 266.379 with prediabetes and a reference cohort of 2.556.928 subjects. T2D and prediabetes were associated with higher risk of PD (HRadjusted 1.19, 95%CI 1.13–1.25, and 1.07, 1.00–1.14; respectively). In analyses stratified by sex, prediabetes was only associated with PD risk in women (1.12, 1.03–1.22 vs. 1.01, 0.99–1.10 in men). When analysis was stratified by age, T2D and prediabetes were associated with a greater PD risk both in women (2.36, 1.96–2.84 and 2.10, 1.70–2.59 respectively) and men (1.74, 1.52–2.00 and 1.90, 1.57–2.30 respectively) below 65 years-old. Conclusions We report for the first time that prediabetes increases the odds of subsequent PD and replicate the association with established T2D. Both associations predominate in women and young individuals.