HbA1c and Motor Outcome in Parkinson's Disease in the Mark-PD Study.

Abstract

With great interest, we have read the study by Markaki and colleagues reporting that not only high, but also low glycated hemoglobin (HbA1c) levels may be associated with motor progression in Parkinson's disease (PD).1 A recent meta-analysis published in this journal revealed a significantly increased risk of developing PD in patients with type 2 diabetes mellitus.2 Furthermore, this group and others have reported an association of diabetes with faster motor progression in patients with PD.2, 3 In line with these findings, Markaki and colleagues reveal that a high HbA1c level (≥42 mmol/mL, n = 18) was a strong and significant predictor of unfavorable motor outcome (Hoehn & Yahr stage ≥ 3). Interestingly, patients with low HbA1c levels (≤30 mmol/mol, n = 17) also had a faster motor progression in this study, although less pronounced. Therefore, we evaluated the association of HbA1c level with motor outcome in the Biomarkers in Parkinson's Disease (Mark-PD) study, which is a prospective hospital-based clinical study with bio-bank.4 HbA1c level and motor outcome were available in 86 patients with PD (age, 65.7 ± 8.9 years; male, 65.1%; disease duration, 12 years [7–15.5 years]; follow-up, 516 days [377–711 days]). We used the same HbA1c categorization as Markaki and colleagues, but regardless of prevalent diabetes because of small sample size. Furthermore, motor progression was defined as MDS-UPDRS part III increase of >4 points, as previously described.5 During follow-up, we registered 44 cases with motor progression. In Kaplan–Meier analysis, we observed a linear trend across the 3 HbA1c categories, that is, the higher the HbA1c level, the faster the motor progression (log rank for linear trend: P = 0.08; Fig. 1A). Comparing only the lowest and highest HbA1c groups with each other in unadjusted and adjusted Cox regression analysis, we observed faster motor progression in patients within the highest HbA1c group (≥42 mmol/mL, n = 16; Fig. 1B). Taken together, we confirm findings by Markaki and colleagues that high HbA1c may be associated with an unfavorable motor outcome. Although the group of PD patients with low HbA1c was underpowered in our study (n = 6), this group showed rather a trend toward an even longer motor progression-free survival. 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 ± 158 days), 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) Research project: A. Conception, B. Organisation, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing the first draft, B. Review and Critique. S.Z.: 1C, 2B, 2C, 3B M.U.: 1C, 2B, 2C, 3B S.L.: 2A, 2B, 2C, 3B C.G.: 2C, 3B C.C.: 1A, 1B, 1C, 2A, 2B, 2C, 3A