Conclusion
Our study suggests that increased ratio of global O-GlcNAcylation to tau phosphorylation at Thr212 site in the whole blood is associated with decreased risk of MCI, especially with better memory function in T2DM subjects. Clinical
Methods
Sociodemographic, clinical characteristics and cognitive performances of the enrolled T2DM subjects were extensively assessed. Global O-GlcNAcylation and tau phosphorylation levels in the whole blood were also determined using Western blot.
Objective
Aberrant O-GlcNAc modification has been implicated in type 2 diabetes mellitus (T2DM) and the pathogenesis of neurodegenerative diseases via competition with tau phosphorylation. We aimed to investigate the association between global O-GlcNAcylation, tau phosphorylation levels and mild cognitive impairment (MCI) in the whole blood of patients with T2DM.
Results
Forty-eight T2DM subjects, including 24 with MCI and 24 with normal cognition, were enrolled in this study. Compared with cognitively normal controls, T2DM with MCI subjects displayed decreased global O-GlcNAcylation level, but increased tau phosphorylation levels (all p < 0.05). To reflect the combined effect, the ratios of global O-GlcNAcylation to tau phosphorylation levels, including specific sites, such as Ser396, Ser404, Thr212, and Thr231, were all significantly decreased in MCI subjects (all p < 0.05). Further multivariable logistic regression analysis revealed that high glycated hemoglobin A1c was an independent risk factor, whereas increased O-GlcNAc/p-T212 was an independent protective factor for MCI in patients with T2DM (odds ratio [OR] = 2.452, 95% confidence interval [CI] 1.061-5.668, p = 0.036; OR = 0.028, 95%CI 0.002-0.388, p = 0.008, respectively). With regard to each cognitive domain, O-GlcNAc/p-T212 was positively correlated with the score of Auditory Verbal Learning Test-delayed recall (r = 0.377, p = 0.010).
Trial registration
www.ClinicalTrials.gov, identifier ChiCTR-OCC-15006060.