期刊
BMJ OPEN
卷 9, 期 9, 页码 -出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/bmjopen-2019-031586
关键词
Type 1 diabetes; Type 2 diabetes; Classification; C-peptide; GADA; IA-2A; Type 1 Diabetes Genetic Risk Score
资金
- Exeter NIHR Clinical Research Facility
- UK Medical Research Council [MR/N00633X/]
- NIHR Exeter Clinical Research Facility
- National Institute for Health Research (NIHR) (UK) [DRF-2010-03-72]
- Diabetes UK Harry Keen Fellowship [16/0005529]
- Wellcome Trust [102820/Z/13/Z]
- NIHR Clinician Scientist award [CS-2015-15-018]
- National Institute for Health Research (NIHR)
- MRC [MC_PC_15047] Funding Source: UKRI
Objective To develop and validate multivariable clinical diagnostic models to assist distinguishing between type 1 and type 2 diabetes in adults aged 18-50. Design Multivariable logistic regression analysis was used to develop classification models integrating five pre-specified predictor variables, including clinical features (age of diagnosis, body mass index) 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 UK cohorts recruited from primary and secondary care. Participants 1352 (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 <200 pmol/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 >600 pmol/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. 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 to 0.93) (clinical features only) to 0.97 (95% CI 0.96 to 0.98) (all predictors) with low prediction error. Results were consistent in external validation (clinical features and GADA ROC AUC 0.93 (0.90 to 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.
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