Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18 to 50 years
dc.contributor.author | Lynam, A | |
dc.contributor.author | McDonald, T | |
dc.contributor.author | Hill, A | |
dc.contributor.author | Dennis, J | |
dc.contributor.author | Oram, R | |
dc.contributor.author | Pearson, E | |
dc.contributor.author | Weedon, M | |
dc.contributor.author | Hattersley, A | |
dc.contributor.author | Owen, K | |
dc.contributor.author | Shields, B | |
dc.contributor.author | Jones, A | |
dc.date.accessioned | 2019-09-06T13:59:53Z | |
dc.date.issued | 2019-09-26 | |
dc.description.abstract | Objective: To develop and validate multivariable clinical diagnostic models to assist distinguishing between type 1 and type 2 diabetes in adults aged 18 to 50. Design: Multivariable logistic regression analysis was used to develop classification models integrating five pre-specified predictor variables, including clinical features (age of diagnosis, BMI) and clinical biomarkers (GADA and Islet Antigen 2 islet autoantibodies, Type 1 Diabetes Genetic Risk Score), to identify type 1 diabetes with rapid insulin requirement using data from existing cohorts. Setting: United Kingdom cohorts recruited from primary and secondary care. Participants: 1,352 (model development) and 582 (external validation) participants diagnosed with diabetes between the age of 18 and 50 years of white European origin. Main outcome measures: Type 1 diabetes was defined by rapid insulin requirement (within 3 years of diagnosis) and severe endogenous insulin deficiency (C-peptide <200pmol/L). Type 2 diabetes was defined by either a lack of rapid insulin requirement or, where insulin treated within 3 years, retained endogenous insulin secretion (C-peptide >600pmol/L at ≥5 years diabetes duration). Model performance was assessed using area under the receiver operating characteristic curve (ROC AUC), and internal and external validation. 4 Results: Type 1 diabetes was present in 13% of participants in the development cohort. All five predictor variables were discriminative and independent predictors of type 1 diabetes (p<0.001 for all) with individual ROC AUC ranging from 0.82 to 0.85. Model performance was high: ROC AUC range 0.90 [95%CI 0.88, 0.93] (clinical features only) to 0.97 [0.96, 0.98] (all predictors) with low prediction error. Results were consistent in external validation (clinical features and GADA ROC AUC 0.93 [0.90, 0.96]). Conclusions: Clinical diagnostic models integrating clinical features with biomarkers have high accuracy for identifying type 1 diabetes with rapid insulin requirement, and could assist clinicians and researchers in accurately identifying patients with type 1 diabetes. | en_GB |
dc.description.sponsorship | National Institute for Health Research (NIHR) | en_GB |
dc.description.sponsorship | European Community FP7 | en_GB |
dc.description.sponsorship | Oxford Hospitals Charitable Fund | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.identifier.citation | Published online 26 September 2019 | en_GB |
dc.identifier.doi | 10.1136/bmjopen-2019-031586 | |
dc.identifier.grantnumber | CS-2015-15-018 | en_GB |
dc.identifier.grantnumber | HEALTH-F2-2008-223211 | en_GB |
dc.identifier.grantnumber | MR/N00633X/ | en_GB |
dc.identifier.grantnumber | DRF-2010-03-72 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/38565 | |
dc.language.iso | en | en_GB |
dc.publisher | BMJ Publishing Group | en_GB |
dc.relation.url | https://exetercrfnihr.org/about/exeter-10000-prb/ | en_GB |
dc.rights | © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. | |
dc.subject | Type 1 diabetes | en_GB |
dc.subject | Type 2 diabetes | en_GB |
dc.subject | Classification | en_GB |
dc.subject | C-peptide | en_GB |
dc.subject | GADA | en_GB |
dc.subject | IA-2A | en_GB |
dc.subject | Type 1 Diabetes Genetic Risk Score | en_GB |
dc.title | Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18 to 50 years | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-09-06T13:59:53Z | |
dc.identifier.issn | 2044-6055 | |
dc.description | This is the final version. Available on open access from BMJ Publishing Group via the DOI in this record | en_GB |
dc.identifier.journal | BMJ Open | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-08-21 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-08-21 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-09-06T13:56:27Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-11-12T14:49:38Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.