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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 25, 2016; 7(2): 14-26
Published online Jan 25, 2016. doi: 10.4239/wjd.v7.i2.14
Brain changes in diabetes mellitus patients with gastrointestinal symptoms
Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Adam D Farmer, Christina Brock, Jens B Frøkjær, Klaus Krogh, Asbjørn M Drewes
Anne M Drewes, Eirik Søfteland, Georg Dimcevski, Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway
Anne M Drewes, Adam D Farmer, Centre for Digestive Diseases, Blizard Institute of Cell and Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AJ, United Kingdom
Adam D Farmer, Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, Straffordshire ST4 6QG, United Kingdom
Christina Brock, Jens B Frøkjær, Asbjørn M Drewes, Mech-Sense, Department of Gastroenterology and Hepatology and Clinical Institute, Aalborg University Hospital, 9100 Aalborg, Denmark
Jens B Frøkjær, Department of Radiology, Aalborg University Hospital, 9100 Aalborg, Denmark
Klaus Krogh, Neurogastroenterology Unit, Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8000 Aarhus, Denmark
Author contributions: Each author contributed to this paper in regard to design of the study, literature review and analysis, critical revision and editing; all authors had approved to the final version.
Conflict-of-interest statement: The authors confirm that this article content has no conflict of interest. No financial support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Asbjørn M Drewes, PhD, DMSc, Professor, Mech-Sense, Department of Gastroenterology and Hepatology and Clinical Institute, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. amd@rn.dk
Telephone: +45-97-660000
Received: July 13, 2015
Peer-review started: July 24, 2015
First decision: August 25, 2015
Revised: September 14, 2015
Accepted: October 23, 2015
Article in press: October 24, 2015
Published online: January 25, 2016
Processing time: 182 Days and 8.7 Hours
Abstract

Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system (CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal (GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testing mainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes, especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation.

Keywords: Diabetes mellitus; Gastrointestinal; Electroencephalogram; Magnetic resonance imaging; Brain

Core tip: Investigation of the existing literature on diabetes patients with gastrointestinal (GI) symptoms indicates the presence of structural and functional brain changes. This was most consistent in electrophysiological studies, where especially changes in the insula seemed to correlate with GI symptoms. Imaging studies confirmed the electrophysiological findings showing microstructural changes in brain areas involved in visceral sensory processing. Due to these findings, future targets in treatment of GI symptoms in patients with diabetes may be based on modulation of central nervous system reorganisation, either pharmacologically or with afferent nerve stimulation.