Zinc transporter 8 autoantibody testing requires age-related cut-offs.

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 (

Parental experiences of a diagnosis of neonatal diabetes and perceptions of newborn screening for glucose: a qualitative study.

Neonatal diabetes presents <6 months of life but delays in recognition result in presentation with life-threatening hyperglycaemia/diabetic ketoacidosis. Early identification and rapid genetic diagnosis is crucial and ensures correct treatment/management. Adding 'glucose' to newborn bloodspot screening (NBS) could aid prompt detection but requires evidence of parental acceptance. OBJECTIVES: Increase understanding of parental experience of presentation/recognition of neonatal diabetes and perceptions of glucose testing within NBS. SETTING: UK families confirmed with a genetic diagnosis of neonatal diabetes, November 2014-2018, were invited to participate. PARTICIPANTS: In-depth qualitative interviews were conducted with 10 parents of 14 children. 8 had transient neonatal diabetes: KCNJ11 (n=5), ABCC8 (n=1), 6q24 (n=2), 6 had permanent neonatal diabetes: KCNJ11 (n=4), INS (n=1), homozygous GCK (n=1). PRIMARY AND SECONDARY OUTCOME MEASURES: Interviews audio recorded, transcribed and subjected to thematic content analysis. RESULTS: 3 key themes emerged:Babies were extremely ill at hospital admission, with extended stays in intensive care required.Identification of diabetes was not 'standardised' and perceived a 'chance' finding.Adding glucose to NBS was universally considered extremely positive. CONCLUSIONS: Diagnosis of neonatal diabetes is frequently delayed, resulting in critically ill presentation with prolonged intensive care support, additional healthcare costs and familial distress. Potential to detect hyperglycaemia earlier was universally endorsed by parents with no negative consequences identified. Although further study including a larger number of individuals is needed to confirm our findings this study provides the first evidence of acceptability of glucose testing fulfilling Wilson-Jungner criteria for implementation within the NBS programme.

Strategies to identify individuals with monogenic diabetes: results of an economic evaluation.

OBJECTIVES: To evaluate and compare the lifetime costs associated with strategies to identify individuals with monogenic diabetes and change their treatment to more appropriate therapy. DESIGN: A decision analytical model from the perspective of the National Health Service (NHS) in England and Wales was developed and analysed. The model was informed by the literature, routinely collected data and a clinical study conducted in parallel with the modelling. SETTING: Secondary care in the UK. PARTICIPANTS: Simulations based on characteristics of patients diagnosed with diabetes <30 years old. INTERVENTIONS: Four test-treatment strategies to identify individuals with monogenic diabetes in a prevalent cohort of diabetics diagnosed under the age of 30 years were modelled: clinician-based genetic test referral, targeted genetic testing based on clinical prediction models, targeted genetic testing based on biomarkers, and blanket genetic testing. The results of the test-treatment strategies were compared with a strategy of no genetic testing. PRIMARY AND SECONDARY OUTCOME MEASURES: Discounted lifetime costs, proportion of cases of monogenic diabetes identified. RESULTS: Based on current evidence, strategies using clinical characteristics or biomarkers were estimated to save approximately £100-£200 per person with diabetes over a lifetime compared with no testing. Sensitivity analyses indicated that the prevalence of monogenic diabetes, the uptake of testing, and the frequency of home blood glucose monitoring had the largest impact on the results (ranging from savings of £400-£50 per person), but did not change the overall findings. The model is limited by many model inputs being based on very few individuals, and some long-term data informed by clinical opinion. CONCLUSIONS: Costs to the NHS could be saved with targeted genetic testing based on clinical characteristics or biomarkers. More research should focus on the economic case for the use of such strategies closer to the time of diabetes diagnosis. TRIAL REGISTRATION NUMBER: NCT01238380.