Glycated Hemoglobin A1c, Cerebral Small Vessel Disease Burden, and Disease Severity in Parkinson's Disease

Objective: Our study aimed to investigate the glucose levels in PD and controls. We also examine whether glucose control is associated with PD severity regardless of diabetic status, and test whether the correlation is mediated by cerebral small vessel disease (CSVD) burden.

Methods: A total of 100 patients with idiopathic PD and 100 age- and sex-matched controls who underwent brain magnetic resonance imaging (MRI) were enrolled in this study. We collected the clinical data and blood parameters, including fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), and blood lipid. Patients with PD were divided into early (n = 61) and advanced (n = 39) subgroups, based on Hoehn and Yahr (H&Y) stages. Differences between the PD and controls, PD with and without diabetes, and between two PD subgroups were compared. CSVD markers were assessed, including lacunes, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. Multivariable logistic regressions were used to test the association between HbA1c and H&Y stages. Interaction between HbA1c and CSVD burden in relation to H&Y stages was also analyzed.

Results: PD group exhibited higher HbA1c (p < 0.001), lower high-density lipoprotein cholesterol (p < 0.001) and triglyceride (p = 0.049) than controls. Advanced PD patients showed higher HbA1c than early PD group (p = 0.022). Increasing HbA1c (OR = 1.54, 95% CI 1.03-2.32, p = 0.036) along with longer disease duration (OR = 1.14, 95% CI 1.01-1.27, p = 0.028) and higher UPDRS III score (OR = 1.07, 95% CI 1.02-1.11, p = 0.002) increased the risk of belonging to the higher H&Y stage. However, interaction between HbA1c and CSVD burden in relation to H&Y stages was not significant.

Interpretation: HbA1c is independently associated with H&Y stages in PD, and this correlation may not be mediated by CSVD burden.