Objective: To investigate peripheral insulin resistance and cerebral FDG-PET changes in Parkinson’s disease (PD).

Background: Glycated hemoglobin levels (HbA1c) is used as a marker of peripheral insulin resistance. High HbA1c is associated with higher mortality in individuals with diabetes and cardiovascular diseases. Preclinical and in vivo studies support a role for insulin resistance in PD pathogenesis. Despite FDG-PET abnormalities being common in PD, to date, no studies have investigated the link between HbA1c and FDG-PET changes in early PD, and their relationship with PD severity.

Method: A total of 37 non-diabetic people with PD were recruited at Cedars-Sinai Medical Center from the ongoing, single-center Phase II clinical trial of liraglutide for PD (NCT02953665). Participants had at least 2 years disease duration and/or were confirmed by DaTscan, were responsive to levodopa or dopaminergic treatment, and had no signs of cognitive impairment (Mattis Dementia Rating Scale-2 score > 120). HbA1c was correlated with age, disease duration, severity of motor and non-motor symptoms, and FDG-PET abnormalities. For each subject, the FDG-PET was completed within 30 days of clinical assessments. Presence of insulin resistance was defined as HbA1c equal to or above 5.7%.

Results: Individuals with PD and insulin resistance (PD-IR) had lower global FDG-PET uptake compared to patients with PD and no insulin resistance (PD-NoIR) (5.1±0.78 in 16 PD-IR vs.5.8±1.2 in 21 PD-NoIR, p=0.047). Higher HbA1c was associated with lower mean cerebral FDG-PET imaging (r=-0.365, p-value=0.029, Figure 1). Higher MDS-UPDRS part III OFF was associated with higher mean cerebral FDG-PET SUVmean (r=0.365, p-value=0.029, Figure 2), in particular in the locus coeruleus (r= 0.435, p-value=0.008, Figure 3).

Conclusion: Peripheral insulin resistance is associated with impairment in cerebral metabolism rate. Hyperactive metabolism of the locus coeruleus and global cerebral uptake is associated with greater motor burden, which suggests that therapies that can restore insulin resistance, such as liraglutide, might slow Parkinson’s disease progression by improving cerebral metabolism impairment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/insulin-resistance-and-parkinsons-disease/