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

BMJ 2011; 343 doi: (Published 07 July 2011) Cite this as: BMJ 2011;343:d4092
  1. Juliet A Usher-Smith, academic clinical fellow1,
  2. Matthew J Thompson, senior clinical scientist2,
  3. Stephen J Sharp, senior statistician3,
  4. Fiona M Walter, clinical lecturer in general practice1
  1. 1General Practice and Primary Care Research Unit, University of Cambridge, Cambridge CB2 0SR, UK
  2. 2Department of Primary Health Care, University of Oxford, Oxford OX3 7LF, UK
  3. 3MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge CB2 0QQ
  1. Correspondence to: J Usher-Smith jau20{at}
  • Accepted 13 May 2011


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.


  • We thank Isla Kuhn, Reader Services Librarian, University of Cambridge Medical Library, for her help developing the search strategy and Professor David Dunger for helpful advice throughout the study and for proofreading the manuscript.

  • Contributors: JAUS performed the literature search, selected articles for inclusion, extracted the data, performed the analysis, and wrote the first draft of the manuscript. FMW and MJT selected articles for inclusion, extracted the data, and reviewed and edited the manuscript. SJS assisted with the statistical analysis and reviewed and edited the manuscript.

  • Funding: JAUS is supported by an NIHR academic clinical fellowship and FW by an NIHR clinical lectureship. MJT is funded by NIHR programme grant “Development and implementation of new diagnostic processes and technologies in primary care,” and SJS is employed by the MRC.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Data sharing: No additional data available.

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