Research Papers:

Cognition, serum BDNF levels, and BDNF Val66Met polymorphism in type 2 diabetes patients and healthy controls

Yan-Feng Zhen, Xing-Yu Liu, Dong-Hao Zhou, Xiangdong Du, Guangzhong Yin, Yingyang Zhang, Hui Fang _, Gang Xu, Jair C. Soares and Xiang Yang Zhang

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Oncotarget. 2018; 9:3653-3662. https://doi.org/10.18632/oncotarget.23342

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Yan-Feng Zhen1,*, Xing-Yu Liu2,*, Dong-Hao Zhou3,*, Xiangdong Du4, Guangzhong Yin4, Yingyang Zhang4, Hui Fang1, Gang Xu5, Jair C. Soares6 and Xiang Yang Zhang6

1Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, China

2Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, China

3Department of Endocrinology, Linyi People’s Hospital, Linyi, China

4Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China

5Department of Burn, Tangshan Gongren Hospital, Tangshan, China

6Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA

*These authors contributed equally to this work

Correspondence to:

Hui Fang, email: [email protected]

Xiang Yang Zhang, email: [email protected]

Keywords: type 2 diabetes; brain-derived neurotrophic factor; cognition; polymorphism; association

Received: August 05, 2017     Accepted: November 23, 2017     Published: December 16, 2017


Background and aims: Type 2 diabetes (T2DM) is associated with cognitive deficits. However, their pathophysiological mechanisms are still unknown. Recent study suggests that brain-derived neurotrophic factor (BDNF) is correlated with cognitive deficits in T2DM patients. This study was to determine whether altered serum BDNF levels and cognitive deficits depended on the BDNF Val66Met polymorphism in T2DM.

Results: The BDNF Val66Met polymorphism may not contribute directly to the susceptibility to T2DM. The total and nearly all index scores (all p < 0.01) except for the attention and visuospatial/constructional indexes (both p > 0.05) of RBANS were markedly decreased in T2DM compared with healthy controls. Serum BDNF levels were significantly lower in patients than that in controls (p < 0.001), and BDNF was positively associated with delayed memory in patients (p < 0.05). The Met variant was associated with worse delayed memory performance among T2DM patients but not among normal controls. Moreover, serum BDNF was positively associated with delayed memory among Met homozygote patients (β = 0.29, t = 2.21, p = 0.033), while serum BDNF was negatively associated the RBANS total score (β = –0.92, t = –3.40, p = 0.002) and language index (β = −1.17, t = –3.54, p = 0.001) among Val homozygote T2DM patients.

Conclusions: BDNF gene Val66Met variation may be associated with cognitive deficits in T2DM, especially with delayed memory. The association between lower BDNF serum levels and cognitive impairment in T2DM is dependent on the BDNF Val66Met polymorphism.

Methods: We recruited 311 T2DM patients and 346 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), serum BDNF levels, and the BDNF Val66Met polymorphism.

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