Objective: aim of the study was to investigate whether diabetes mellitus influences nigrostriatal dopaminergic vulnerability in drug-naïve patients with early-stage Parkinson’s Disease (PD).

Background: recently, diabetes mellitus (DM) has been associated with neurodegenerative damage in nigrostriatal regions and dopaminergic dysfunctions [1,2]. This nigrostriatal vulnerability may be the common underlying process between PD and DM [3]. However, few studies tested this association in vivo.

Method: the study included 97 patients with PD: n=27 patients with diabetes mellitus (PD-DM), and n=70 without diabetes mellitus (PD-noDM). All subjects underwent a clinical and neurological examination and performed Brain SPECT to measure brain dopamine transporter (DAT) density. Spatially normalized DAT-SPECT scans underwent the occipital-adjusted specific binding to obtain parametric data. The ANCOVA test was applied to test differences in ¹²³I-FP-CIT binding between groups, considering age, sex, disease duration, and SSRI treatment as covariance of nuisance. The same analysis was conducted on a subset of n=27 PD-noDM matched 1:1 with PD-DM for motor impairment.

Results: PD-DM and PD-noDM patients were comparable for age, sex, disease duration, motor severity presence of tremor, and SSRI treatment. The ANCOVA test showed that PD-DM patients had higher dopamine uptake in left putamen, as compared to PD-noDM. The same analyses, performed on matched PD for age, sex and motor severity revealed that PD-DM patients exhibited a higher dopamine uptake in left putamen dompared to PD-noDM.

Conclusion: findings showed that diabetes mellitus may impact on compensatory mechanisms of nigrostriatal systems resulting in less dopamine deficits even with comparable degree of motor impairment.

References: [1] Gennaro Pagano, Sotirios Polychronis, Heather Wilson, Beniamino Giordano, Nicola Ferrara, Flavia Niccolini, Marios Politis Neurology May 2018, 90 (19) e1654-e1662; DOI:10.1212/WNL.0000000000005475

[2] Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 2004;3:169–178.

[3] Pérez-Taboada, I., Alberquilla, S., Martín, E. D., Anand, R., Vietti-Michelina, S., Tebeka, N. N., Cantley, J., Cragg, S. J., Moratalla, R., & Vallejo, M. (2020). Diabetes Causes Dysfunctional Dopamine Neurotransmission Favoring Nigrostriatal Degeneration in Mice. Movement disorders : official journal of the Movement Disorder Society, 35(9), 1636–1648. https://doi.org/10.1002/mds.28124

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diabetes-impact-on-nigrostriatal-vulnerability-in-parkinsons-disease/