Diabetes, High A1C Linked With Increased Cognitive Impairment in PD

New research published in Movement Disorders reveas that in patients with Parkinson disease (PD), diabetes and high glycated hemoglobin (A_1C) were associated with increased neuroaxonal damage and cognitive impairment.

Previous studies have found an association between diabetes and PD prevalence and incidence, while higher A_1C has been shown to be an independent risk factor of faster motor progression and been linked with motor impairment.

Furthermore, “interventional trials using antidiabetic drugs indicate that there might be a causal relationship between glycemic control and motor severity in PD patients,” the authors wrote.

To better elucidate the 2 conditions’ relationship to neuroaxonal damage (ie, serum neurofilament light chain [NfL]) in PD, the investigators assessed data from the observational prospective Biomarkers in Parkinson’s Disease (MARK-PD) study.

A total of 195 patients with PD over the age of 18 were included in the current analysis; any patient with a documented diabetes diagnosis or recorded use of antidiabetic drugs was classified as having the disease.

Blood samples were collected at baseline, while motor and cognitive functions were assessed using the Hoehn & Yahr (H&Y) or Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) and Montreal Cognitive Assessment [MoCA], respectively. Medical records were used to identify vascular comorbidities.

Data showed patients with PD and diabetes were more likely to have hypertension, hypercholesterolemia, and prior stroke compared with patients without diabetes. Those with A_1C levels above the median of 36.6 mmol/mol were also more likely to have hypertension and hypercholesterolemia, were significantly older, and had higher Nfl levels.

The researchers found:

• A Spearman analysis showed A_1C levels correlated with MoCA score and NfL levels, but not with disease duration, MDS-UPDRS III, or H&Y stages
• An unadjusted linear regression analysis revealed prevalent diabetes or A_1C levels were inversely associated with cognition (MoCA scores), but this association only remained significant for prevalent diabetes after adjustment
• There was a significant association of prevalent diabetes with H&Y stages in unadjusted and age/body mass index (BMI)-adjusted models, which revealed only a trend after adjustment for vascular risk factors (P = .079)
• In unadjusted linear regression models, diabetes was associated with higher serum NfL levels in patients with PD, and this remained significant after adjustment for age, BMI, prevalent hypertension, hypercholesterolemia, and history of stroke
• Although A_1C levels were significantly correlated with NfL levels in age- and BMI-adjusted models, this association revealed only a trend after adjustment for vascular risk factors (P = .075)

“The association between diabetes and serum NfL was significant in all models, suggesting a robust and independent relationship,” the authors wrote.

Past research also indicated PD incidence in patients with diabetes is dependent on the treatment target of antidiabetic drugs, as “different hormones and glucose-lowering signaling pathways seem to have different effects on neuronal function,” they continued.

Patients with PD may also have a higher insulin resistance, which could contribute to PD’s pathology.

Models of A_1C were underpowered in the current analysis, potentially accounting for the lack of significant association of A_1C with neuroaxonal damage (NfL) and cognition (MoCA) seen post adjustment.

The study’s small sample size and potential colinearity between the examined variables mark limitations to the analysis.

Overall, data indicated increased neuroaxonal damage in patients with PD and diabetes is independent of vascular risk factors, while “the association of high A_1C with neuroaxonal damage is not independent of vascular risk factors,” the researchers concluded, assing that hyperglycemia may explain some of the association between PD and diabetes, but not all.

Reference

Uyar M, Lezius S, Buhmann C, et al. Diabetes, glycated hemoglobin (HbA1C), and neuroaxonal damage in Parkinson’s disease (MARK-PD study). Mov Disord. Published online April 6, 2022. doi:10.1002/mds.29009