Rachel Besser

I work as a consultant paediatrician at Oxford Children’s Hospital and I am the Subtheme Lead for the Oxford NIHR Biomedical Research Centre (BRC) 4, “Translating experimental medicine into state-of-the art care”.

I work in translational research, which means research which directly effects the care of children, young people, and adults with diabetes. My passion is type 1 diabetes (T1D), an autoimmune disease which results in lack of insulin. I was inspired to work in diabetes when I was diagnosed with T1D aged 9. My drive comes from wanting to improve the lives of individuals with T1D, and that ranges from preventing T1D to improving ways of living with the condition.

A big focus of my work is in identifying children early before they need treatment for T1D, to help prepare for a smoother transition, or a ‘softer landing’, to insulin therapy. I lead the T1Early Programme, and this is what the programme is all about (see below). As therapies become available to delay T1D, it will be important to know who the at-risk children and adults are, who could benefit from these. 

We are grateful to receive funding from NIHR, Diabetes UK and the UKRI for our work.

T1 Early programme  

Central to our work is implementation into clinical care. Our research aims to understand the feasibility, acceptability, and cost effectiveness of screening for T1D in the NHS.

Background

Around 3000 children are diagnosed with T1D every year in England and Wales and require lifelong insulin injections. In most cases the early symptoms go unrecognised, and children are very unwell at diagnosis, often needing hospital admission. Thirty-eight percent of children are already in a life-threatening condition called diabetic ketoacidosis (DKA), where the level of a chemical called ketones rises which can be dangerous. DKA needs to be treated in hospital and needs careful management. The rate of DKA is increasing, despite public awareness campaigns. The shock of severe illness is distressing to children and their families and may also have longer term effects on the child’s developing brain, health and well-being.

It is now possible to identify children before they develop symptoms through a finger prick blood test. This picks up markers in the blood, called ‘antibodies’, months of years before symptoms appear. It is also possible to identify children at risk of developing T1D, by testing for genes associated with this condition.

Research from around the world suggests that testing healthy children (‘screening’) for antibodies can prevent emergency admissions and DKA. However, we do not know the best approach, in terms of the age to screen, whether genetics should be included, whether screening is acceptable to the general population, how to follow up children / adults who are identified as at risk in routine clinical care, or whether this is cost effective in the NHS. 

Several UK research platforms screen for IAb, and longitudinal studies (e.g. TEDDY/TrialNet) suggest ~40% loss to follow-up, leaving individuals unsupported and at risk of diabetic ketoacidosis. Increasingly individuals are screened in clinical care, but there is no consensus on the support needs or follow up outside a research study.

Our work aims to find out the answers, through a number of different research studies.

UK-Islet autoantIbody registry (UKIAb)

Establishing an Islet Autoantibody Positive Registry for children and adults in the UK: the UK-Islet Antibody registry

Funder: Diabetes UK

Lead: Dr Rachel Besser, Co-lead Dr Loredana Marcovecchio

Launched: May 2024, Recruitment open from October 2024

Contact email: ukiab@ndm.ox.ac.uk

AIMS

To create a UK registry of IAb-positive children, young people, and adults (CYPA), to:

1. Retain contact with IAb positive individuals.

2. Offer participation in trials testing prevention, support, and new treatments.

3. Understand the lived experience of being IAb positive, and determine individuals’ information and support needs.

4. Collect UK data on progression to clinical disease and resource use.

Objectives:

• Co-produce recommendations for healthcare professionals.
• Co-produce a position statement with members of the public/Diabetes UK on the support needed by people with positive IAb.
• Undertake data linkage with routinely collected clinical datasets to describe resource use.
• Validate existing tools for risk progression developed from international registries.

Impact: This research will improve the support available for individuals with preT1D and facilitate rapid recruitment into T1D prevention trials.

T1Early Feasibility study

Establishing the feasibility of antibody screening in primary care at the time of the pre-school vaccination, to identify children with early-onset type 1 diabetes

Funder: NIHR Oxford BRC 

Chief Investigator: Dr Rachel Besser

Launched: September 2022

Summary

Our proof of concept study is now published! A finger prick blood test was collected to measure islet antibodies form children aged 3.5-4 years when they attended for their pre school vaccination. 

We are now expanding this work more widely.

Study raises hope of pre-school type 1 diabetes screening programme — Department of Paediatrics (ox.ac.uk)

NIHR Programme Development grant 

Screening for pre-clinical type 1 diabetes to prevent hospital admission and acute illness at diagnosis: determining the evidence for benefit, acceptability and elements relevant to cost evaluation

Funder: National Institute for Health Research (NIHR)

Lead: Dr Rachel Besser, Co-lead: Professor Colin Dayan

Launched: October 2022

URL: https://fundingawards.nihr.ac.uk/award/NIHR203948

Follow up in children and young people identified as at risk of future type 1 diabetes

Redesigning the pathway to diagnosis in childhood type 1 diabetes 

Funder: NovoNordisk Research Foundation UK

DPhil student: Dr Rabbi Swaby

Supervisors: Dr Rachel Besser, Professor Colin Dayan, Professor John Todd

Launched: September 2022

URL: https://www.novonordiskfoundation.org.uk/fellowship/research-fellowships-in-clinical-diabetes.html  

EDENT1FI

As part of the screening effort, I am working with colleagues as part of a huge European initiative called EDENT1FI, co-leading WP3 on how to follow up children with T1D, in  a way that is informative, but also practical.

URL: https://www.edent1fi.eu/

Besser REJ, Griffin KJ. Transitioning to Stage 3 Type 1 diabetes: when to start insulin. The lancet Diabetes & Endocirnology 2024, online first

Scudder C, Townson J, Bowen-Morris J, Gillespie K, Evans P, Jones S, Thomas NPB, Stanford J, Fox R, Todd JA, Greenfield S, Dayan CM, Besser REJ. General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit: a proof-of-concept study (the T1Early study). Arch Dis Child. 2024 Jun 26:archdischild-2023-326697. PMID: 38925883.

Phillip M, Achenbach P, Addala A, Albanese-O'Neill A, Battelino T, Bell KJ, Besser REJ, Bonifacio E, Colhoun HM, Couper JJ, Craig ME, Danne T, de Beaufort C, Dovc K, Driscoll KA, Dutta S, Ebekozien O, Elding Larsson H, Feiten DJ, Frohnert BI, Gabbay RA, Gallagher MP, Greenbaum CJ, Griffin KJ, Hagopian W, Haller MJ, Hendrieckx C, Hendriks E, Holt RIG, Hughes L, Ismail HM, Jacobsen LM, Johnson SB, Kolb LE, Kordonouri O, Lange K, Lash RW, Lernmark Å, Libman I, Lundgren M, Maahs DM, Marcovecchio ML, Mathieu C, Miller KM, O'Donnell HK, Oron T, Patil SP, Pop-Busui R, Rewers MJ, Rich SS, Schatz DA, Schulman-Rosenbaum R, Simmons KM, Sims EK, Skyler JS, Smith LB, Speake C, Steck AK, Thomas NPB, Tonyushkina KN, Veijola R, Wentworth JM, Wherrett DK, Wood JR, Ziegler AG, DiMeglio LA. Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes. Diabetes Care. 2024 Aug 1;47(8):1276-1298. PMID: 38912694.

Besser REJ, Long AE, Owen KR, Law R, Birks JS, Pearce O, Williams CL, Scudder CL, McDonald TJ, Todd JA. Transdermal Blood Sampling for C-Peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes. Diabetes Care. 2024 Feb 1;47(2):239-245. PMID: 38087932.

Besser REJ, Bell KJ, Couper JJ, Ziegler AG, Wherrett DK, Knip M, Speake C, Casteels K, Driscoll KA, Jacobsen L, Craig ME, Haller MJ. ISPAD clinical practice consensus guidelines 2022: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes. 2022 Sep 30. doi: 10.1111/pedi.13410. PMID: 36177823.

Houben J, Janssens M, Winkler C, Besser REJ, Dzygalo K, Fehn A, Hommel A, Lange K, Elding Larsson H, Lundgren M, Roloff F, Snape M, Szypowska A, Weiss A, Zapardiel-Gonzalo J, Ziegler AG, Casteels K; GPPAD study group. The emotional well-being of parents with children at genetic risk for type 1 diabetes before and during participation in the POInT-study. Pediatr Diabetes. 2022 Nov 2. doi: 10.1111/pedi.13448. PMID: 36323590.

Sims EK, Besser REJ, Dayan C, Geno Rasmussen C, Greenbaum C, Griffin KJ, Hagopian W, Knip M, Long AE, Martin F, Mathieu C, Rewers M, Steck AK, Wentworth JM, Rich SS, Kordonouri O, Ziegler AG, Herold KC; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022 Apr 1;71(4):610-623. doi: 10.2337/dbi20-0054. PMID: 35316839; PMCID: PMC9114719.

Carr ALJ, Inshaw JRJ, Flaxman CS, Leete P, Wyatt RC, Russell LA, Palmer M, Prasolov D, Worthington T, Hull B, Wicker LS, Dunger DB, Oram RA, Morgan NG, Todd JA, Richardson SJ, Besser REJ. Circulating C-Peptide Levels in Living Children and Young People and Pancreatic β-Cell Loss in Pancreas Donors Across Type 1 Diabetes Disease Duration. Diabetes. 2022 Jul 1;71(7):1591-1596. doi: 10.2337/db22-0097. PMID: 35499624; PMCID: PMC9233242.

Besser REJ, Ng SM, Gregory JW, Dayan CM, Randell T, Barrett T. General population screening for childhood type 1 diabetes: is it time for a UK strategy? Arch Dis Child. 2022 Sep;107(9):790-795. doi: 10.1136/archdischild-2021-321864. Epub 2021 Nov 5. PMID: 34740879.

Besser REJ, Ng SM, Robertson EJ. Screening children for type 1 diabetes. BMJ. 2021 Dec 29;375:e067937. doi: 10.1136/bmj-2021-067937. PMID: 34965925.