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      Evaluation of the correlation between type 1 diabetes and cognitive function in children and adolescents, and comparison of this correlation with structural changes in the central nervous system: a study protocol

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          Abstract

          Introduction

          Diabetes mellitus type 1 (T1DM) affects nearly 15 million children worldwide and failure to achieve and maintain good glycaemic control in this group can lead to diabetes-related complications. Children with T1DM can experience impairment in cognitive function such as memory, attention and executive function. This study is designed to evaluate the correlation between diabetes and cognitive dysfunction as well as to clarify whether this correlation can be linked to neurological structural changes in 6–11-year-old children with diabetes.

          Methods and analysis

          310 eligible children with diabetes will be divided into two groups based on glycaemic control according to their HbA1c index. The control group will include 150 children aged 6–11 without diabetes. The following parameters will be measured and investigated: duration of the disease since diagnosis, required daily insulin dose, frequency of insulin administration, hospital admissions due to diabetes, hypoglycaemic episodes during the last year, and episodes of diabetic ketoacidosis. The following components of cognitive function will be evaluated: memory, attention, executive function, decision-making and academic performance. Cognitive function and subsequent subtests will be assessed using Cambridge Neuropsychological Test Automated Battery (CANTAB) tools. Brain structural indices such as intracranial vault (ICV), as well as cerebrospinal fluid (CSF), ventricle, hippocampus, total intracranial, total brain, grey matter and white matter volume will be measured using MRI. ANOVA, correlational tests (Spearman) and regression models will be used to evaluate the hypothesis.

          Ethics and dissemination

          This study is approved by the ethics committee of the Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences (TUMS) under reference number 00300. Our findings are to be published in a peer-reviewed journal and disseminated both electronically and in print.

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          Epidemiology of type 1 diabetes.

          David Maahs, Nancy West, Jean M Lawrence … (2010)
          This article describes the epidemiology of type 1 diabetes mellitus (T1D) around the world and across the lifespan. Epidemiologic patterns of T1D by demographic, geographic, biologic, cultural, and other factors in populations are presented to gain insight about the causes, natural history, risks, and complications of T1D. Data from large epidemiologic studies worldwide indicate that the incidence of T1D has been increasing by 2% to 5% worldwide and that the prevalence of T1D is approximately 1 in 300 in the United States by 18 years of age. Research on risk factors for T1D is an active area of research to identify genetic and environmental triggers that could potentially be targeted for intervention. Although significant advances have been made in the clinical care of T1D with resultant improvements in quality of life and clinical outcomes, much more needs to be done to improve care of, and ultimately find a cure for, T1D. Epidemiologic studies have an important ongoing role to investigate the complex causes, clinical care, prevention, and cure of T1D. Copyright 2010 Elsevier Inc. All rights reserved.
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            A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children.

            Laura Chaddock, Kirk I Erickson, Ruchika Prakash … (2010)
            Because children are becoming overweight, unhealthy, and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether higher- and lower-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was also positively associated with performance on the relational but not the item memory task. Furthermore, bilateral hippocampal volume was found to mediate the relationship between fitness level (VO(2) max) and relational memory. No relationship between aerobic fitness, nucleus accumbens volume, and memory was reported, which strengthens the hypothesized specific effect of fitness on the hippocampus. The findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain. Copyright © 2010 Elsevier B.V. All rights reserved.
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              Cognitive Function in Children With Type 1 Diabetes

              Patricia Gaudieri, Rusan Chen, Tammy Greer … (2008)
              OBJECTIVE—To quantify the magnitude and pattern of cognitive difficulties in pediatric type 1 diabetes as well as the effects associated with earlier disease onset and severe hypoglycemia. RESEARCH DESIGN AND METHODS—Pediatric studies of cognitive function since 1985 were identified for study inclusion using MEDLINE and PsycInfo. Effect size (ES, Cohen's d) between the diabetic and control groups, expressed in SD units, were calculated within cognitive domains to standardize meta-analysis test performance. RESULTS—The meta-analysis sample of 2,144 children consisted of 1,393 study subjects with type 1 diabetes and 751 control subjects from 19 studies. Overall, type 1 diabetes was associated with slightly lower overall cognition (ES −0.13), with small differences compared with control subjects across a broad range of domains, excluding learning and memory, which were similar for both groups. Learning and memory skills, both verbal and visual (−0.28 and −0.25), were more affected for children with early-onset diabetes (EOD) than late-onset diabetes (LOD), along with attention/executive function skills (−0.27). Compared with nondiabetic control subjects, EOD effects were larger, up to one-half SD lower, particularly for learning and memory (−0.49). Generally, seizures were associated with a negligible overall cognition ES of −0.06, with slight and inconsistent cognitive effects found on some measures, possibly reflecting the opposing effects of poorer versus better metabolic control. CONCLUSIONS—Pediatric diabetes generally relates to mildly lower cognitive scores across most cognitive domains. Cognitive effects are most pronounced and pervasive for EOD, with moderately lower performance compared with control subjects. Seizures are generally related to nominal, inconsistent performance differences.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2016
                Publication date (Electronic): 28 April 2016
                Volume: 6
                Issue: 4
                Electronic Location Identifier: e007917
                Affiliations
                [1 ]Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences , Tehran, Iran
                [2 ]Department of Psychiatry, Rouzbeh Hospital, Tehran University of Medical Sciences , Tehran, Iran
                [3 ]Faculty of Psychology and Education, Allameh Tabataba'ee University , Tehran, Iran
                [4 ]Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences , Tehran, Iran
                Author notes
                [Correspondence to ] Dr Bagher Larijani; larijanib@ 123456tums.ac.ir
                Article
                Publisher ID: bmjopen-2015-007917
                DOI: 10.1136/bmjopen-2015-007917
                PMC ID: 4853982
                PubMed ID: 27126974
                SO-VID: 87aeafc1-b2d8-492b-be82-7928f59d317e
                Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
                License:

                This is an Open Access article 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/

                History
                Date received : 19 February 2015
                Date revision received : 30 November 2015
                Date accepted : 1 December 2015
                Categories
                Subject: Diabetes and Endocrinology
                Subject: Protocol
                Subject: 1506
                Subject: 1843
                Subject: 1719

                ScienceOpen disciplines: Medicine
                Data availability:
                ScienceOpen disciplines: Medicine

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