Association of peripheral inflammatory cytokines with motor and non-motor symptoms in patients with Parkinson’s disease and type 2 diabetes mellitus

Aiping Hu¹Yuqing She¹Xue Cao¹Yang Wang¹Shu Wu¹Juan Lu¹Yang Zhao^2*Lizhi Yu¹Haifeng Jiang¹Qing Chen²

• ¹Nanjing Pukou People’s Hospital, Nanjing, Jiangsu Province, China
• ²Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China

Objective: This pilot study aims to investigate the association between peripheral inflammatory cytokines and motor and non-motor symptoms in patients with both Parkinson's disease (PD) and type 2 diabetes mellitus (T2DM) and the underlying mechanisms. Methods: Sixty patients with PD were divided into two groups depending on whether they also had T2DM, resulting in a PD group (21 cases) and a PD–T2DM group (39 cases). Thirty healthy volunteers from the physical examination centre were enrolled as the control group. Peripheral blood was collected from all patients. Results: Patients with PD–T2DM had higher Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III scores; total MDS-UPDRS scores; Parkinson’s Disease Questionnaire-39 (PDQ-39) scores; and interleukin (IL)-6, IL-1β, tumour necrosis factor alpha (TNF-α) and IL-4 levels than patients with PD (p < 0.05). In the PD group, IL-4 levels correlated with UPDRS II (r = 0.337), Non-Motor Symptom Scale (r = 0.354), Hamilton Depression Scale (r = 0.420) and PDQ-39 (r = 0.423) scores (p < 0.05). A multivariate regression revealed IL-6 independently predicted lower UPDRS III scores (β = –0.497, p = 0.018), TNF-α correlated with PD duration (β = 0.689, p < 0.001) and IL-1β correlated with PDQ-39 scores (β = 0.462, p = 0.002) in patients with PD–T2DM. Adjusted models explained up to 52.3% of variance (adjusted R²). In the PD group, age-adjusted correlations confirmed IL-4 was associated with UPDRS II (r = 0.321, p = 0.047) and PDQ-39 (r = 0.418, p = 0.009), and interferon gamma (IFN-γ) was associated with Scales for Outcomes in Parkinson’s Disease-Autonomic Questionnaire (SCOPA-AUT) (r = –0.564, p = 0.001). Negative correlations were identified between IL-6 and UPDRS III scores (r = −0.497) and IFN-γ and SCOPA-AUT scores (r = −0.588) (p < 0.05). Conclusion: These pilot findings suggest peripheral inflammatory cytokines can be considered biomarkers in patients with PD–T2DM. The underlying mechanism by which T2DM worsens the motor and non-motor symptoms of PD may involve increased inflammation.