PMID- 30837891
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 10
DP  - 2019
TI  - Increased Ratio of Global O-GlcNAcylation to Tau Phosphorylation at Thr212 Site 
      Is Associated With Better Memory Function in Patients With Type 2 Diabetes.
PG  - 110
LID - 10.3389/fphys.2019.00110 [doi]
LID - 110
AB  - 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. 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. 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). 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 Trial 
      Registration: www.ClinicalTrials.gov, identifier ChiCTR-OCC-15006060.
FAU - Huang, Rong
AU  - Huang R
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Tian, Sai
AU  - Tian S
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Han, Jing
AU  - Han J
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
FAU - Cai, Rongrong
AU  - Cai R
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Lin, Hongyan
AU  - Lin H
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Guo, Dan
AU  - Guo D
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Wang, Jiaqi
AU  - Wang J
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Wang, Shaohua
AU  - Wang S
AD  - Department of Endocrinology, Affiliated Zhongda Hospital, Southeast University, 
      Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20190214
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6382671
OTO - NOTNLM
OT  - O-GlcNAcylation
OT  - mild cognitive impairment
OT  - phosphorylation
OT  - tau protein
OT  - type 2 diabetes mellitus
EDAT- 2019/03/07 06:00
MHDA- 2019/03/07 06:01
PMCR- 2019/02/14
CRDT- 2019/03/07 06:00
PHST- 2018/08/24 00:00 [received]
PHST- 2019/01/30 00:00 [accepted]
PHST- 2019/03/07 06:00 [entrez]
PHST- 2019/03/07 06:00 [pubmed]
PHST- 2019/03/07 06:01 [medline]
PHST- 2019/02/14 00:00 [pmc-release]
AID - 10.3389/fphys.2019.00110 [doi]
PST - epublish
SO  - Front Physiol. 2019 Feb 14;10:110. doi: 10.3389/fphys.2019.00110. eCollection 
      2019.