Rachel Besser

About me

I work as a consultant paediatrician at Oxford Children’s Hospital https://www.ouh.nhs.uk/childrens-diabetes/information/research.aspx, 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 within Professor John Todd’s research group at the Wellcome Centre for Human Genetics, University of Oxford.

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. I am Principal Investigator for POINT UK, (Primary Oral Insulin Trial), which examines whether the development of T1D can be prevented in children with an increased genetic risk, through preventive treatment with oral insulin, with the hope of training the immune system so that it tolerates its own insulin.

I also undertake collaborative work on closed loop (artificial pancreas) systems in children with established T1D, and immunotherapy.  These include the recently completed ITAD (IL-2) immunotherapy trial.

T1 Early programme  

We are undertaking research to understand feasibility, acceptability, cost effectiveness and implementation 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. 1 in 4 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. On average one child dies each year because of DKA. The rate of DKA has not changed over the last 20 years, 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.

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

T1Early Feasibility study

Title: 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

We are currently recruiting children between the age of 3.5-4years initially in two GP practices, in the Thames Valley, before further rollout, to test for early markers of T1D. This involves a finger prick blood test to measure for diabetes antibodies.

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

NIHR Programme Development grant 

Title: 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

Summary

We will review the evidence for different methods of screening and the benefits and harms of diagnosing T1D early. We will explore the acceptability of screening with a group of parents, children and young people, and specifically we will interview parents for the T1Ealry feasibility study. Finally, we will explore what the costs and potential savings of screening might be for the NHS. We will use this information in a future Programme Grant to select the best approach for screening for the NHS.

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

Title: Redesigning the pathway to diagnosis in childhood type 1 diabetes (T1D)

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  

Summary

Screening on its own does not reduce life threatening illness. It is screening accompanied by appropriate follow up. Children identified with diabetes antibodies need regular testing to see if they are developing T1D, but the best methods to do this are uncertain. Around 50% children and adults are lost to follow up in established T1D follow up research studies. This is likely because of the tests used and the variable time period between an individual being told they are ‘at risk’ and getting clinical T1D.

To understand how best to care for these children, we will undertake research to establish a general population surveillance pathway in children at high risk of developing T1D in childhood.

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.