Objective: We used blood-based markers of neuroaxonal damage, inflammation, and glycaemic control to examine whether Type 2 Diabetes (T2D) is linked to a more severe Parkinson’s Disease (PD) phenotype. We also assessed the relationship between these biomarkers and clinical symptom severity to try to understand whether glycaemic control or inflammation drive symptom severity in PD patients with T2D.

Background: T2D is a risk factor for PD and PD severity, with inflammation and glycaemic control both potential drivers of this relationship [1-6].

Method: Patients with PD both with T2D (n = 45) and without T2D (n = 73), and healthy controls (HCs) (n = 42) were recruited from the East London Parkinson’s Disease (ELPD) project. Participants underwent venous blood sampling, dried blood spot (DBS) sampling, and a full clinical assessment including MDS-UPDRS III and MoCA. Venous blood samples were analysed for plasma levels of neurofilament light chain (NfL), pro-inflammatory cytokines (IFN-γ, IL-6, IL-1β and TNF-α), and C-Reactive Protein (CRP). Dried blood spot samples were analysed for glycated haemoglobin (HbA1c).

Results: In PD patients, plasma NfL was elevated (259.1 vs. 153.8 pg/mL; p < 0.001) whilst plasma IFN-γ was reduced (6.90 vs. 9.81 pg/mL; p = 0.009), with trends towards elevated plasma IL-6 (2.09 vs. 1.76 pg/mL; p = 0.028) and TNF-α (2.03 vs. 1.72 pg/mL; p = 0.073) compared with controls. Except for IFN-γ, significance was lost after age adjustment.

In PD patients with T2D, trends towards elevated plasma IL-6 (2.53 vs. 1.99 pg/mL; p = 0.044) and TNF-α (2.33 vs. 1.94 pg/mL; p = 0.051) were observed compared to PD without T2D, with the TNF-α trend persisting after age adjustment (p = 0.053).

In age- and disease duration-adjusted regression, PD patients with T2D showed strong correlations between plasma NfL and MoCA (p = 0.005) and MDS UPDRS-III (p = 0.006), which were weaker or absent in those without T2D and controls.

Conclusion: These data suggest increased peripheral inflammation (TNF-α) in PD patients with T2D, supporting the role of inflammation in the overlap between PD and T2D. Regression analyses show a stronger link between plasma NfL and symptom severity in PD patients with T2D compared to without T2D. Future studies should examine longitudinal changes in inflammation, neuroaxonal damage, and glycaemic control in people with PD and T2D.

References: [1] Chohan, Harneek, Konstantin Senkevich, Radhika K. Patel, Jonathan P. Bestwick, Benjamin M. Jacobs, Sara Bandres Ciga, Ziv Gan-Or, and Alastair J. Noyce. ‘Type 2 Diabetes as a Determinant of Parkinson’s Disease Risk and Progression’. Movement Disorders 36, no. 6 (2021): 1420–29.

[2] Markaki, Ioanna, Theodora Ntetsika, Kimmo Sorjonen, Per Svenningsson, and BioPark Study Group. ‘Euglycemia Indicates Favorable Motor Outcome in Parkinson’s Disease’. Movement Disorders: Official Journal of the Movement Disorder Society 36, no. 6 (June 2021): 1430–34.

[3] Zittel, Simone, Merve Uyar, Susanne Lezius, Christian Gerloff, and Chi-un Choe. ‘HbA1c and Motor Outcome in Parkinson’s Disease in the Mark-PD Study’. Movement Disorders 36, no. 8 (2021): 1991–92.

[4] Huxford, Brook, Tahrina Haque, Aaron Ben Joseph, Cristina Simonet, David Gallagher, Caroline Budu, Ruth Dobson, and AlastairJ Noyce. ‘Parkinson’s Disease and Type 2 Diabetes: HbA1c Is Associated with Motor and Cognitive Severity’. Movement Disorders: Official Journal of the Movement Disorder Society 37, no. 2 (February 2022): 427–28. 5
Vijiaratnam, Nirosen, Michael Lawton, Raquel Real, Amanda J. Heslegrave, Tong Guo, Dilan Athauda, Sonia Gandhi, et al. ‘Diabetes and Neuroaxonal Damage in Parkinson’s Disease’. Movement Disorders 37, no. 7 (2022): 1568–69.

[5] Uyar, Merve, Susanne Lezius, Carsten Buhmann, Monika Pötter-Nerger, Robert Schulz, Stephanie Meier, Christian Gerloff, Jens Kuhle, and Chi-un Choe. ‘Diabetes, Glycated Hemoglobin (HbA1c), and Neuroaxonal Damage in Parkinson’s Disease (MARK-PD Study)’. Movement Disorders 37, no. 6 (2022): 1299–1304

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MDS Abstracts - https://www.mdsabstracts.org/abstract/parkinsons-disease-and-type-2-diabetes-severity-a-case-control-biomarker-study/