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World J Diabetes. May 15, 2023; 14(5): 481-493
Published online May 15, 2023. doi: 10.4239/wjd.v14.i5.481
Diabetes mellitus type 2 as an underlying, comorbid or consequent state of mental disorders
Milica M Borovcanin, Katarina Vesic, Ivica Petrovic, Ivan P Jovanovic, Nataša R Mijailović
Milica M Borovcanin, Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
Katarina Vesic, Department of Neurology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
Ivica Petrovic, Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
Ivan P Jovanovic, Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
Nataša R Mijailović, Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
Author contributions: Borovcanin MM presented the concept of the manuscript and discussed it with all contributors; authors contributed equally to the writing subsections by their specific competencies; Borovcanin MM wrote the preliminary version; and all contributors gave suggestions and approval for the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Milica M Borovcanin, MD, PhD, Associate Professor, Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34 000, Serbia. milicaborovcanin@yahoo.com
Received: December 14, 2022
Peer-review started: December 14, 2022
First decision: March 14, 2023
Revised: March 21, 2023
Accepted: April 12, 2023
Article in press: April 12, 2023
Published online: May 15, 2023
Processing time: 151 Days and 16.8 Hours
Abstract

Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.

Keywords: Diabetes mellitus type 2; Mental disorders; Neuroinflammation; Neurodegeneration; Cognition

Core Tip: Mental disorders and type 2 diabetes mellitus (T2DM) are common, chronic, and frequently comorbid diseases that contribute significantly to global disability and mortality. Substantial evidence on the association between mental disorders and T2DM has been gathered over the past decade. In this review, we presented the latest cellular and molecular mechanisms of the shared pathways of T2DM and mental disorders, including neuroendocrine alterations and inflammation, immune response, oxidative stress, gut dysbiosis and gut-brain axis dysregulation, along with the hypothalamic-pituitary-adrenal axis dysregulation. The bidirectional link between mental disorders and T2DM underlines the importance of treating these disorders together rather than separately.