Type 2 Diabetes in Parkinson Disease Associates With Neuroaxonal Damage

Parkinsons disease nerve cells. Computer illustration of human nerve cells affected by Lewy bodies (small red spheres inside cytoplasm of neurons) in the brain of a patient with Parkinsons disease. Lewy bodies are abnormal accumulations of protein that develop inside nerve cells in Parkinsons disease, Lewy Body Dementia, and some other neurological disorders.
Letter authors sought to evaluate the relationship between diabetes mellitus and neurofilament light concentrations in a subgroup of participants in the MARK-PD study.
Significant associations were identified between neurofilament light and diabetes status in patients with Parkinson disease.

Parkinson disease (PD) and diabetes mellitus (DM) comorbidities are associated with more severe neuroaxonal damage, according to a letter published in Movement Disorders.

The Biomarkers in Parkinson’s Disease (MARK-PD) study found an inverse relationship between DM and cognitive and motor status as well as increased serum neurofilament light (NfL) concentrations which is a marker for neuroaxonal damage.

Motivated by the published results, the letter authors evaluated the relationship between DM and NfL in their Tracking Parkinson’s dataset.

Among the 280 patients in their study1, 29 had type 2 DM. The patients with PD-DM were older (mean, 74.1 vs 68.1 years; P <.001), had higher body mass index (BMI) (mean, 31.1 vs 27.1 kg/m2; P <.001), and increased vascular risk (P =.032) compared with patients who had PD without DM, respectively.

The PD-DM cohort had a mean serum NfL level of 39.5 and the PD without DM cohort had 29.6 (P <.001). In the fully adjusted regression analysis, NfL was significantly increased in PD-DM (coefficient, 0.52; 95% CI, 0.18-0.86; P =.003).

The letter authors concluded that the relationship between PD-DM and elevated serum NfL levels was confirmed in 2 independent PD cohorts. Similar pathological processing, including neuroinflammation, lysosomal dysfunction, insulin resistance, and mitochondrial dysfunction are observed in PD and DM. These processes may all lead to neurodegeneration. Additional study is needed to disentangle the mechanistic factors which contribute to progressive axonal damage in PD.

“[Type 2 DM] and PD share several pathological processes encompassing neuroinflammation, lysosomal dysfunction, mitochondrial dysfunction, and the development of central insulin resistance that leads to neurodegeneration,” the letter authors wrote.

In a response to this letter2, the authors of the original paper pointed out that the 2 PD cohorts had differing disease durations (12 years vs 1 year), Hoehn & Yahr stages (2.5 vs 1.8), and Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale III scores (26 vs 23). Despite these differences, they both found increased neuronal damage defined as elevated serum NfL.

The original paper authors posited that the similarly elevated serum NfL in both early and late PD-DM may be caused by different types of neuronal damage. They supported this speculation with evidence from previous studies which have found elevated NfL among patients with PD who had cognitive impairment as well as those with motor impairment. These trends warrant additional investigation.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

This article originally appeared on Neurology Advisor


  1. Vijiaratnam N, Lawton M, Real R, et al. Diabetes and neuroaxonal damage in Parkinson’s disease. Mov Disord. Published online July 20, 2022. doi:10.1002/mds.29067
  2. Buhmann C, Pötter-Nerger M, Schulz R, Gerloff C, Kuhle J, Choe C-U. Reply to: “Diabetes and neuroaxonal damage in Parkinson’s disease”. Mov Disord. Published online July 20, 2022. doi:10.1002/mds.29064