dc.contributor.author | Grace, SL | |
dc.contributor.author | Cooper, A | |
dc.contributor.author | Jones, AG | |
dc.contributor.author | McDonald, TJ | |
dc.date.accessioned | 2021-08-06T12:59:51Z | |
dc.date.issued | 2021-08-04 | |
dc.description.abstract | INTRODUCTION: Zinc transporter 8 autoantibodies (ZnT8A) are biomarkers of beta cell autoimmunity in type 1 diabetes that have become more widely available to clinicians in recent years. Robust control population-defined thresholds are essential to ensure high clinical specificity in islet autoantibody testing. We aimed to determine the optimal cut-offs for ZnT8A testing. RESEARCH DESIGN AND METHODS: 97.5th and 99th centile cut-offs were determined using residual clinical sera from 1559 controls aged between 0 and 83 years with no history of diabetes and a hemoglobin A1c level of less than 6.0% (<42 mmol/mol). ZnT8A were measured by ELISA (RSR, Cardiff, UK) on a Dynex DS2 ELISA robot (Dynex, Preston, UK). We assessed the impact of age-related cut-offs in comparison with the manufacturer's recommended threshold in a mixed cohort of young-onset (<age 30) diabetes (UNITED study (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes), n=145). RESULTS: Using the manufacturer's limit of detection, 6 WHO U/mL, 16.2% of people in the control cohort had detectable levels of ZnT8A and those who had detectable ZnT8A were much more likely to be younger (p<0.0001). The 97.5th and 99th centile thresholds were substantially higher in younger participants: 18 and 127 WHO U/mL (tested under 30 years) in comparison with 9 and 21 WHO U/mL (tested 30 years and over). In the UNITED cohort some of those found to be ZnT8A-positive by the manufacturer's threshold but negative using the appropriate 99% centile cut-off (127 WHO U/mL) displayed characteristics suggestive of type 2 diabetes. CONCLUSIONS: Age-related thresholds are needed for ZnT8A testing. In those aged <30 years, use of manufacturers' recommended cut-offs may result in low test specificity and potentially high rates of false positive test results in patients who do not have autoimmune diabetes. | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.description.sponsorship | Research England | en_GB |
dc.identifier.citation | Vol. 9, article e002296 | en_GB |
dc.identifier.doi | 10.1136/bmjdrc-2021-002296 | |
dc.identifier.grantnumber | CS-2015-15-018 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/126694 | |
dc.language.iso | en | en_GB |
dc.publisher | BMJ Publishing Group | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/34348918 | en_GB |
dc.rights.embargoreason | © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. | en_GB |
dc.rights | https://creativecommons.org/licenses/by-nc/4.0/ | en_GB |
dc.subject | autoantibodies | en_GB |
dc.subject | autoimmunity | en_GB |
dc.subject | biomarkers | en_GB |
dc.subject | diabetes mellitus | en_GB |
dc.subject | type 1 | en_GB |
dc.title | Zinc transporter 8 autoantibody testing requires age-related cut-offs | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-08-06T12:59:51Z | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version. Available on open access from BMJ Publishing Group via the DOI in this record | en_GB |
dc.description | Data availability statement:
Data are available upon reasonable request | en_GB |
dc.identifier.eissn | 2052-4897 | |
dc.identifier.journal | BMJ Open Diabetes Research and Care | en_GB |
dc.rights.uri | http://www.rioxx.net/licenses/all-rights-reserved | en_GB |
dcterms.dateAccepted | 2021-07-17 | |
exeter.funder | ::National Institute for Health Research (NIHR) | en_GB |
exeter.funder | ::Research England | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-08-04 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-08-06T12:53:31Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2021-08-06T12:59:59Z | |
refterms.panel | A | en_GB |