Alterations in effective connectivity within the Papez circuit are correlated with insulin resistance in T2DM patients without mild cognitive impairment

  • Wenqing Xia
  • Yu-Chen Chen
  • Yong Luo
  • Danfeng Zhang
  • Huiyou Chen
  • Jianhua MaEmail author
  • Xindao YinEmail author


Insulin resistance (IR) can significantly affect the hippocampus, a component of a larger memory circuit called the Papez circuit. This study was performed to identify altered effective connectivity within the Papez circuit in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) and to determine the relationships between these alterations and IR. T2DM patients without MCI (n = 105) and age-, sex-, and education-matched healthy controls (n = 106) were included in this study. Granger causality analysis (GCA) with seed regions in the hippocampus was performed to identify abnormal effective connectivity in the brains of T2DM patients without MCI. Furthermore, correlation analysis was conducted to detect the association between aberrant effective connectivity and IR in T2DM patients without MCI. Compared to healthy controls, T2DM patients without MCI demonstrated abnormal directional connectivity both to and from the hippocampus; the main abnormalities were located in several brain areas, including the cingulate cortex, amygdala, and prefrontal cortex, all of which are components of the Papez circuit. This altered effective connectivity network in the Papez circuit was correlated with IR in T2DM patients without MCI. Effective connectivity network alterations within the Papez circuit occurred prior to the appearance of mild cognitive deficits in T2DM patients and were correlated with IR. The current study may improve our understanding of the IR-related neurological mechanisms involved in T2DM.


Type 2 diabetes mellitus Insulin resistance Effective connectivity Papez circuit 



This work was supported by the National Natural Science Foundation of China (No. 81870563), Natural Science Foundation of Jiangsu Higher Education Institutions (No. 18KJB320007), Medical Science and Technology Development Foundation of Nanjing Department of Health (No. YKK16140), Jiangsu Provincial Special Program of Medical Science (BE2017614), Youth Medical Talents of Jiangsu Province (No. QNRC2016062), and 14th “Six Talent Peaks” Project of Jiangsu Province (No. YY-079).

Compliance with ethical standards

Conflict of interests

The authors declare that there is no potential conflict of interests regarding the publication of this paper.

Ethical approval

The current study was approved by the Research Ethics Committee of the Nanjing Medical University.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology, Nanjing First HospitalNanjing Medical UniversityNanjingChina
  2. 2.Department of Radiology, Nanjing First HospitalNanjing Medical UniversityNanjingChina

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