Screening to prevent type 1 diabetes
By the time the physical symptoms of type 1 diabetes (T1D) appear – the classic triad of increased urination, thirst and weight loss – the autoimmune attack on the body’s beta cells is already well underway. A diagnosis at this stage is too late for many families, with up to 30% of newly diagnosed children in Australia experiencing diabetic ketoacidosis (DKA) due to a missed or delayed diagnosis.1
However, behind the physical signs of T1D, chemicals markers in the blood act as signposts of the silent autoimmune processes taking place. These markers – known as islet autoantibodies – may have been present for months, or even years, and offer the chance to screen for T1D risk before symptoms begin. When combined with new drugs in development that can delay T1D onset, a screening program has the potential to not only reduce the risk of DKA, but ultimately eliminate the threat of T1D for future generations.
The benefits of T1D screening
Screening and early intervention are growing focus areas for T1D research, as Australia shifts towards a more preventative approach to healthcare. Australia currently has three national screening programs – for bowel cancer, breast cancer and cervical cancer. Bowel cancer screening alone is estimated to prevent 59,000 deaths by 2040.2 So how would a screening program for T1D work, and what kind of impact could it have on how the condition is diagnosed, managed, and prevented?
T1D screening uses a blood test to look for autoantibodies against pancreatic islet cells. People who have two or more islet autoantibodies, but are otherwise asymptomatic, are defined as having stage 1 T1D.3 This subclinical stage can last for months or years, but most people with multiple islet autoantibodies will eventually develop T1D.4
Diagnosing T1D at this initial stage, rather than after the onset of physical symptoms, could significantly reduce the risk of DKA. In addition to being a serious complication that causes significant psychological stress for families, DKA leads to poorer long-term outcomes for people with T1D, and can be fatal.5 Children diagnosed through autoantibody screening have a lower risk of developing DKA than those diagnosed through traditional pathways – results from a study of more than 90,000 children in Germany showed a rate of DKA of less than 5%, compared with the usual rate of 20%.6
An islet autoantibody screening program – Type1Screen – is already underway in Australia and New Zealand for people with a relative who has T1D. However, up to 90% of people diagnosed with T1D do not have a first-degree relative with the condition.7 General population screening programs for T1D are being trialled in both the US and Germany,8, 9 and JDRF is planning an Australian-first pilot study to trial a population screening program here. The pilot aims to assess the potential benefits of islet autoantibody screening in Australia, as well as the psychological impacts, and attitudes of healthcare professionals and people with T1D towards the program.
If successful, this pilot could be expanded to a national screening program, where all children in Australia would be screened for T1D risk once they reach a certain age.
Delaying the onset of disease
So, what comes next, for those who test positive for islet autoantibodies? Those who test positive in Type1Screen are put in touch with an endocrinologist, who explains the result and walks through potential next steps.
A positive islet autoantibody result has the potential to cause distress – mothers of children who tested positive for islet autoantibodies in Germany reported a higher level of psychological stress, compared with mothers of children without autoantibodies. However, this stress subsided over time, and was lower than that experienced by parents of children diagnosed with T1D in other studies.6 Pre-screen counselling and clear information on possible outcomes, including careful explanation of risk and probability, are potential ways of moderating distress.10 Participants in Type1Screen currently speak with a research nurse prior to undergoing screening, who explains the testing process and its potential outcomes, as well as addressing any questions or concerns they may have.
As well as beginning monitoring or management at an early stage, people with stage 1 T1D could have the opportunity to enroll in clinical trials of preventative therapies. Many of these drugs are immune therapies, more likely to be effective at early stages of T1D when the body still has a significant number of beta cells remaining.
In 2019, a milestone clinical trial of teplizumab – a monoclonal antibody – was the first ever to show a delay in the onset of T1D.11 Teplizumab delayed disease onset by a median of two years in people at high risk, and researchers are now hoping to replicate the results in a larger phase III study.
This year could bring more milestones for prevention research, with the initiation of an Australian clinical trial of baricitinib – a rheumatoid arthritis drug that has also shown promise in T1D. Baricitinib disrupts a critical pathway in the process of beta cell destruction, and has been shown to prevent and even reverse T1D in mice.12 Baricitinib will now be tested in people with T1D for the first time in the JDRF-funded study.
The benefits of screening for T1D will only increase as more preventative therapies like teplizumab and baricitinib are discovered – it’s hoped that those identified through screening can one day receive a treatment which can slow, or even prevent the development of T1D.
Cause and effect
Over the past decade, our knowledge about what causes T1D has been growing. Understanding the factors that influence disease is critical for prevention research – we need to know how T1D develops to be able to prevent it.
ENDIA is Australia’s largest study into the genetic and environmental factors that cause T1D. It is investigating environmental factors during pregnancy and infancy – things like gut bacteria, nutrition and exposure to viruses – and how these interact with each other, and with a person’s genes, to cause T1D.
ENDIA recently completed recruitment of 1,500 babies, and results from the study are already shedding light on the complex interplay of factors that causes T1D to develop. In 2019, ENDIA researchers found that pregnant women with T1D had a different profile of viruses in their gut, compared with pregnant women without T1D.13 With further investigation, findings like this could form the basis for targeted preventative strategies – like a vaccine against specific viral strains.
In 2019, an Australian study found that the rate of T1D in Australian children has decreased by 15% since the introduction of the rotavirus vaccine in 2007.14 Gut viruses like rotavirus, norovirus and enterovirus have long been speculated to play a role in the development of T1D in some people, and could prove to be promising vaccination targets for those susceptible to the infections.
Find out more about the latest prevention research
To stay up to date on T1D prevention research, including results and progress from the clinical trials mentioned in this article, email email@example.com and ask to be signed up to our quarterly newsletter for health professionals.
Department of Health. Australian National Diabetes Strategy 2016â2020. Canberra: Commonwealth of Australia, 2015. Available from: http:// www.health.gov.au/internet/main/publishing.nsf/Content/nds-2016-2020.
Lew JB et al. Long-term evaluation of benefits, harms, and cost-effectiveness of the National Bowel Cancer Screening Program in Australia: a modelling study. Lancet Public Health. 2017; 2: e331â40
Insel RA et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society and the American Diabetes Association. Diabetes Care. 2015; 38: 1964â1974.4.
Ziegler AG et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013;309(23):2473â2479.
Steck AK et al. Residual beta-cell function in diabetes children followed and diagnosed in the TEDDY study compared with community controls. Pediatr Diabetes 2017; 18: 794â802.6.
Ziegler AG et al. Yield of a pubic health screening of children for islet autoantibodies in Bavaria, Germany. JAMA. 2020; 323(4):339â351.
Couper J, Harrison L. Controversies in medicine: redefining the diagnosis of type 1 diabetes. Med J Aust. 2019; 211(4).8.
Raab J et al. Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study. BMJ Open 2016; 6: e11144.9.
Gesualdo PD et al. Feasibility of screening for T1D and celiac disease in a pediatric clinic setting. Pediatr Diabetes 2016; 17: 441â448.
Johnson SB. Psychological Impact of Screening and Prediction in Type 1 Diabetes. Curr Diab Rep 2011; 11:454-459.
Herold KC et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 2019; 381:603-613.
Trivedi PM et al. Repurposed JAK1/JAK2 inhibitor reverses established autoimmune insulitis in non-obese diabetic mice. Diabetes 2017; 66(6):1650â1660.
Kim WK et al. Distinct gut virome profile of pregnant women with type 1 diabetes in the ENDIA study. Open Forum Infectious Diseases 2019; 6(2).14.
Harrison LC et al. Does rotavirus turn on type 1 diabetes? PLoS Pathog 2019; 15(10):e1007965.