Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Mar 15, 2015; 6(2): 259-270
Published online Mar 15, 2015. doi: 10.4239/wjd.v6.i2.259
Short and long term neuro-behavioral alterations in type 1 diabetes mellitus pediatric population
Edna Litmanovitch, Ronny Geva, Marianna Rachmiel
Edna Litmanovitch, Ronny Geva, the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel
Ronny Geva, Department of Psychology, the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan 5290002, Israel
Marianna Rachmiel, Pediatric and Adolescents, Diabetes Mellitus Service, Division of Pediatrics, Assaf Haroffeh Medical Center, Zerifin 70300, Israel
Marianna Rachmiel, Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
Author contributions: Litmanovitch E substantial contributed to conception and design, acquisition of data, analysis and interpretation of data, drafting the article, and final approval of the version to be published; Geva R substantial contributed to design of review and interpretation of data, revising it critically for important intellectual content, and final approval of the version to be published; Rachmiel M substantial contributed to conception and design, analysis and interpretation of data, revising it critically for important intellectual content, and final approval of the version to be published.
Conflict-of-interest: The authors declare no potential conflicts of interest relevant to this article.
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: Marianna Rachmiel, MD, Head of Pediatric and Adolescents, Diabetes Mellitus Service, Division of Pediatrics (Building 131), Assaf Haroffeh Medical Center, Zerifin section on 44 Road, Zerifin 70300, Israel. rmarianna@gmail.com
Telephone: +972-8-9542007 Fax: +972-8-9779136
Received: August 28, 2014
Peer-review started: August 30, 2014
First decision: November 19, 2014
Revised: December 3, 2014
Accepted: December 16, 2014
Article in press: December 17, 2014
Published online: March 15, 2015
Abstract

Type 1 diabetes mellitus (T1DM) is one of the most prevalent chronic conditions affecting individuals under the age of 18 years, with increasing incidence worldwide, especially among very young age groups, younger than 5. There is still no cure for the disease, and therapeutic goals and guidelines are a challenge. Currently, despite T1DM intensive management and technological interventions in therapy, the majority of pediatric patients do not achieve glycemic control goals. This leads to a potential prognosis of long term diabetic complications, nephrological, cardiac, ophthalmological and neurological. Unfortunately, the neurological manifestations, including neurocognitive and behavioral complications, may present soon after disease onset, during childhood and adolescence. These manifestations may be prominent, but at times subtle, thus they are often not reported by patients or physicians as related to the diabetes. Furthermore, the metabolic mechanism for such manifestations has been inconsistent and difficult to interpret in practical clinical care, as reported in several reviews on the topic of brain and T1DM. However, new technological methods for brain assessment, as well as the introduction of continuous glucose monitoring, provide new insights and information regarding brain related manifestations and glycemic variability and control parameters, which may impact the clinical care of children and youth with T1DM. This paper provides a comprehensive review of the most recently reported behavioral, cognitive domains, sleep related, electrophysiological, and structural alterations in children and adolescences from a novel point of view. The review focuses on reported impairments based on duration of T1DM, its timeline, and modifiable disease related risk parameters. These findings are not without controversy, and limitations of data are presented in addition to recommendations for future research direction.

Keywords: Type 1 diabetes mellitus, Cognitive, Behavioral, Brain, Alterations, Children, Adolescences

Core tip: Neurocognitive and behavioral functions vary with age and depend on interactions between multiple endogenous (brain structure, integrity) and exogenous (metabolic) factors. Understanding of brain development with age is an emerging field of research, and delineation of type 1 diabetes mellitus (T1DM) impact on those processes is even more challenging and unclear. We review the most recent information in a novel format, relevant for clinicians practicing pediatric medicine and diabetologists taking part in clinical oriented research, in order to clarify: what is known, what is its association to modifiable diabetes related aspects, what should clinicians pay attention to, and what is needed in future research. The available studies presented hereby already indicate the need for a change in the care of pediatric population with T1DM. Periodic psychological and neurological ongoing evaluation of children and youth with T1DM, including cognition specific questionnaires and direct testing, should be performed as part of clinical care, especially while taking into account patients’ daily and nocturnal glucose variability.