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      Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review

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          Abstract

          Objective To identify the factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes in children and young adults.

          Design Systematic review.

          Data sources PubMed, EMBASE, Web of Science, Scopus, and Cinahl and article reference lists.

          Study selection Cohort studies including unselected groups of children and young adults presenting with new onset type 1 diabetes that distinguished between those who presented in diabetic ketoacidosis and those who did not and included a measurement of either pH or bicarbonate in the definition of diabetic ketoacidosis. There were no restrictions on language of publication.

          Results 46 studies involving more than 24 000 children in 31 countries were included. Together they compared 23 different factors. Factors associated with increased risk were younger age (for <2 years old v older, odds ratio 3.41 (95% confidence interval 2.54 to 4.59), for <5 years v older, odds ratio 1.59 (1.38 to 1.84)), diagnostic error (odds ratio 3.35 (2.35 to 4.79)), ethnic minority, lack of health insurance in the US (odds ratio 3.20 (2.03 to 5.04)), lower body mass index, preceding infection (odds ratio 3.14 (0.94 to 10.47)), and delayed treatment (odds ratio 1.74 (1.10 to 2.77)). Protective factors were having a first degree relative with type 1 diabetes at the time of diagnosis (odds ratio 0.33 (0.08 to 1.26)), higher parental education (odds ratios 0.4 (0.20 to 0.79) and 0.64 (0.43 to 0.94) in two studies), and higher background incidence of type 1 diabetes (correlation coefficient –0.715). The mean duration of symptoms was similar between children presenting with or without diabetic ketoacidosis (16.5 days (standard error 6.2) and 17.1 days (6.0) respectively), and up to 38.8% (285/735) of children who presented with diabetic ketoacidosis had been seen at least once by a doctor before diagnosis.

          Conclusions Multiple factors affect the risk of developing diabetic ketoacidosis at the onset of type 1 diabetes in children and young adults, and there is potential time, scope, and opportunity to intervene between symptom onset and development of diabetic ketoacidosis for both parents and clinicians.

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          Most cited references59

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          Diabetes

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            PEDIATRICS

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              Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host.

              Enteroviruses are believed to contribute to the pathogenesis of type 1 diabetes mellitus (T1DM). In this Review, the interplay between infection with enteroviruses, the immune system and host genes is discussed. Data from retrospective and prospective epidemiological studies strongly suggest the involvement of enteroviruses, such as coxsackievirus B, in the development of T1DM. Enteroviral RNA and/or proteins can be detected in tissues of patients with T1DM. Isolation of coxsackievirus B4 from the pancreas of patients with T1DM or the presence of enteroviral components in their islets strengthens the hypothesis of a relationship between the virus and the disease. Enteroviruses can play a part in the early phase of T1DM through the infection of beta cells and the activation of innate immunity and inflammation. In contrast with its antiviral role, virus-induced interferon alpha can be deleterious, acting as an initiator of the autoimmunity directed against beta cells. Enteroviruses, through persistent and/or successive infections, can interact with the adaptive immune system. Host genes, such as IFIH1, that influence susceptibility to T1DM are associated with antiviral activities. An increased activity of the IFIH1 protein may promote the development of T1DM. An improved knowledge of the pathogenic mechanisms of enterovirus infections should help to uncover preventive strategies for T1DM.
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                Author and article information

                Contributors
                Role: academic clinical fellow
                Role: senior clinical scientist
                Role: senior statistician
                Role: clinical lecturer in general practice
                Journal
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1468-5833
                2011
                2011
                07 July 2011
                : 343
                : d4092
                Affiliations
                [1 ]General Practice and Primary Care Research Unit, University of Cambridge, Cambridge CB2 0SR, UK
                [2 ]Department of Primary Health Care, University of Oxford, Oxford OX3 7LF, UK
                [3 ]MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge CB2 0QQ
                Author notes
                Correspondence to: J Usher-Smith jau20@ 123456cam.ac.uk
                Article
                ushj845974
                10.1136/bmj.d4092
                3131115
                21737470
                3119c6ec-faa2-46db-bd50-d3778f441a0d
                © Usher-Smith et al 2011

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 13 May 2011
                Categories
                Research
                Epidemiologic Studies
                Quantitative Research
                Immunology (Including Allergy)
                Adolescent Health
                Child Health
                Internet
                Diabetes
                Metabolic Disorders

                Medicine
                Medicine

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