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Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort
  1. Vassiliki Bravis,
  2. Akaal Kaur1,
  3. Helen C Walkey1,
  4. Ian F Godsland1,
  5. Shivani Misra1,
  6. Polly J Bingley2,
  7. Alistair J K Williams2,
  8. David B Dunger3,
  9. Colin M Dayan4,
  10. Mark Peakman5,
  11. Nick S Oliver1,
  12. Desmond G Johnston1
  13. on behalf of the ADDRESS-2 Management Committee, Patient Advocate Group and Investigators
    1. 1 Department of Medicine, Imperial College London, London, UK
    2. 2 School of Clinical Sciences, University of Bristol, Bristol, UK
    3. 3 Department of Paediatrics, University of Cambridge, Cambridge, UK
    4. 4 School of Medicine, Cardiff University, Cardiff, UK
    5. 5 Department of Immunobiology, King’s College London, London, UK
    1. Correspondence to Dr Helen C Walkey; h.walkey{at}imperial.ac.uk

    Abstract

    Objectives To describe the characteristics of children and adults with incident type 1 diabetes in contemporary, multiethnic UK, focusing on differences between the islet autoantibody negative and positive.

    Design Observational cohort study.

    Setting 146 mainly secondary care centres across England and Wales.

    Participants 3312 people aged ≥5 years were recruited within 6 months of a clinical diagnosis of type 1 diabetes via the National Institute for Health Research Clinical Research Network. 3021 were of white European ethnicity and 291 (9%) were non-white. There was a small male predominance (57%). Young people <17 years comprised 59%.

    Main outcome measures Autoantibody status and characteristics at presentation.

    Results The majority presented with classical osmotic symptoms, weight loss and fatigue. Ketoacidosis was common (42%), especially in adults, and irrespective of ethnicity. 35% were overweight or obese. Of the 1778 participants who donated a blood sample, 85% were positive for one or more autoantibodies against glutamate decarboxylase, islet antigen-2 and zinc transporter 8. Presenting symptoms were similar in the autoantibody-positive and autoantibody-negative participants, as was the frequency of ketoacidosis (43%vs40%, P=0.3). Autoantibody positivity was less common with increasing age (P=0.0001), in males compared with females (82%vs90%, P<0.0001) and in people of non-white compared with white ethnicity (73%vs86%, P<0.0001). Body mass index was higher in autoantibody-negative adults than autoantibody-positive adults (median, IQR 25.5, 23.1–29.2vs23.9, 21.4–26.7 kg/m2; P=0.0001). Autoantibody-negative participants were more likely to have a parent with diabetes (28%vs16%, P<0.0001) and less likely to have another autoimmune disease (4%vs8%, P=0.01).

    Conclusions Most people assigned a diagnosis of type 1 diabetes presented with classical clinical features and islet autoantibodies. Although indistinguishable at an individual level, autoantibody-negative participants as a group demonstrated features more typically associated with other diabetes subtypes.

    Trial registration number ISRCTN66496918; Pre-results.

    • general diabetes
    • epidemiology
    • immunology
    • paediatric endocrinology

    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/

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    Footnotes

    • Contributors Literature searches were carried out by VB, HCW, IFG, NSO and DGJ. AK, HCW, IFG, AJKW, PJB, DBD and DGJ were involved in the study design. Data collection was coordinated by AK and HCW. AK, HCW and IFG were responsible for data management. AJKW and PJB were responsible for autoantibody measurements. The statistical analysis plan was developed by IFG. Analysis of the data was by VB, AK and IFG. Data were interpreted by all authors. The manuscript was prepared by authors VB, AK, HCW, IFG, AJKW and DGJ. Critical revisions were made by authors PJB, DBD, CMD, MP and NSO. Figures were prepared by AK, HCW and IFG. The Management Committee oversaw access to the data and stored biological samples. The Patient Advocate Group had input into aspects of study conduct. Local investigators were responsible for the recruitment of participants and collection of data. HCW is the guarantor of this study.

    • Funding The National Institute for Health Research (NIHR) provided the funding for the research infrastructure of the national Clinical Research Network (CRN), with project- specific support from Diabetes UK (grant numbers 09/0003919 and 15/0005234) and the Juvenile Diabetes Research Foundation (grant numbers 9-2010-407 and 3-SRA-2015- 36-A-N). The funders were consulted about the vision for a UK-based type 1 diabetes ascertainment network. The funders are represented on the management committee that oversees access to the data and stored biological samples. The funding was administered as a grant to Imperial College London. Imperial College London is the study Sponsor.

    • Disclaimer The funders had no involvement in study design, data collection, data analysis, data interpretation or writing of the article and took no part in the decision to submit for publication.

    • Competing interests None declared.

    • Patient consent Not required.

    • Ethics approval Ethical approval was obtained from the South Central – Berkshire NHS Research Ethics Committee (reference 10/H0505/85).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement The full anonymous dataset is available to access via a management committee, which includes people living with type 1 diabetes, scientists, clinicians and funder representatives as members. Participants gave informed consent for data sharing subject to conditions described in the access procedure documents available from the study website: www.address2.org.

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