Unfavorable Motor Outcomes in Parkinson Disease Linked to HbA1c Levels

When comparing only the lowest and highest HbA1c groups with each other, unadjusted and adjusted regression analysis indicated faster motor progression in the highest group.

After reviewing previously published research, investigators have confirmed that high hemoglobin (HbA1c) levels may be associated with unfavorable motor outcome in patients with Parkinson disease (PD), warranting future evaluation of the role of glycemic control on PD pathology.1

Senior author Chi-un Choe, MD, Department of Neurology, University Medical Center, and colleagues aimed to confirm the associations of HbA1c level with motor outcomes reported in previous studies. They reported on a subgroup of patients (n = 86) in the Biomarkers in Parkinson’s Disease (Mark-PD) study, a prospective hospital-based biobank. Additionally, they were motivated by findings from Ioanna Markaki, MD, et al which showed that low HbA1c (HR, 2.7 [95% CI, 1.3-6]; P = .01) and high HbA1c (HR, 3.6 [95% CI, 1.5-8.9]; P = .005) are independent predictors of unfavorable motor outcomes.2

Motor progression was defined as Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III increase of at least 4 points. Using Kaplan-Meier analysis on 44 cases with motor progression, investigators observed a linear trend across the 3 HbA1c categories, with the higher HbA1c levels correlating with faster motor progression (log rank for linear trend, P = .08).1

Unadjusted and adjusted Cox regression analysis that compared the HbA1c groups confirmed these findings for both the lowest (≤30 mmol/mL: HR, 9.11 [95% CI, 1.10-75.63]; P = .041) and highest groups (≥42 mmol/mL: HR, 16.62 [95% CI, 1.58-174.65]; P = .019). Despite the low number of patients with low HbA1c (n = 6), data showed a trend toward an even longer motor progression-free survival.

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Original data from Mark-PD showed increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a cohort of 285 patients with PD. In these patients, increased high-sensitivity troponin 1 and NT-proBNP levels were associated with worse motor function at baseline and with motor decline after 1 year.3

Choe et al concluded that "the small sample size, the longer disease duration, the more advanced PD stages, and the MDS-UPDRS part III-based definition of motor progression in our study might be responsible for the difference between studies. Furthermore, our analysis was based on available HbA1c levels closest to study inclusion (24 days [±158]), whereas Markaki and colleagues used the first available HbA1c level from medical records. Nevertheless, the interesting findings by Markaki and colleagues warrant further investigations to elucidate the role of glycemic control on PD pathology."1

Markaki et al’s findings included 244 patients with PD, of whom 17 had low HbA1c (≤30 mmol/mL), 184 were euglycemic (HbA1c 31-41 mmol/mL), 18 had high HbA1c (HbA1c ≥42 mmol/mL), and 25 had diabetes mellitus (DM). Compared to the euglycemic group, those with low HbA1c had HRs of 2.5 (95% CI, 1.2-5.3; P = .01) to reach unfavorable motor outcome. Also, high-HbA1c patients (HR, 3.4 [95% CI, 1.4-8.2]; P = .006) and DM (HR, 2 [95% CI, 1.1-4]; P = .04) were at increased risk of having influence of balance during follow-up. These differences remained significant in all groups except those with DM after adjustment for age, sex, and vascular factors.2

Choe and colleagues also referenced a recently published meta–analysis that found a significantly increased risk of developing PD among patients with type 2 DM (OR, 1.21 [95% CI, 1.07-1.36]. There was also evidence that type 2 DM was associated with faster progression of motor symptoms (standardized mean difference [SMD], 0.55 [95% CI, 0.39-0.72]) and cognitive decline (SMD, –0.92 [95% CI, –1.50 to –0.34]). Using Mendelian randomization, investigators found supportive evidence for causal effect of diabetes on PD risk (inverse-variance weighted method [IVW] OR, 1.08 [95% CI, 1.02-1.14]; P = .010) and some evidence of an effect on motor progression (IVW OR, 1.10 [95% CI, 1.01-1.20]; P = .032) but not on cognitive progression.4

REFERENCES
1. Zittel S, Uyar M, Lezius S, Gerloff C, Choe C. HbA1c and motor outcome in Parkinson disease in the Mark-PD study. Mov Disord. 2021;36(8):1991-1992. doi:10.1002/mds.28689
2. Markaki I, Ntetsika T, Sorjonen K, Svenningsson P. Euglycemia indicates favorable motor outcome in Parkinson disease. Mov Disord. 2021;36(6):1430-1434. doi:10.1002/mds.28545
3. Choe C, Niemann L, Englisch C, et al. Subclinical cardiac microdamage, motor severity, and cognition in Parkinson Disease. Mov Disord. 2020;35(10):1863-1868. doi: 10.1002/mds.28129
4. Chohan H, Senkevich K, Patel RK, et al. Type 2 diabetes as a determinant of Parkinson disease risk and progression. Move Disord. 2021;36(6):1420-1429.. doi: 10.1002/mds.28551