The possibility of universal screening for type 1 diabetes was the theme of a session at this year’s EASD annual meeting in Hamburg, Germany.
The talk was given by Dr Emily K. Sims, Associate Professor of Pediatrics, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.
Research by various groups has established that individuals with multiple islet autoantibodies (biomarkers showing that the body is attacking and killing its own insulin producing beta cells in the pancreas) have a near 100 per cent risk of developing type 1 diabetes over their lifetime.
Multiple groups including Ezio Bonifacio and colleagues from the TEDDY Consortium (Diabetes Care 2021) and Ghalwash and colleagues from Type 1 Diabetes Intelligence Study Group (The Lancet Diabetes & Endocrinology 2022) have shown that screening for islet auto-antibodies at two ages – two and at five to seven years – would predict most cases of type 1 diabetes that would develop by the age of 15.
Dr Sims highlighted that, although screening programs have previously most often focused on people with family members with type 1 diabetes (who can have up to 15 times increased risk of developing the condition), most people who develop type 1 diabetes (85-90 per cent) have no family history of the condition.
She said: “Our knowledge of type 1 diabetes has now evolved from thinking it is a disease that suddenly develops, to knowing that it is something that gradually develops, after the appearance of multiple islet-autoantibodies.
“By screening children and adults to identify individuals with early, presymptomatic stages of disease, we can more accurately predict when they will first need insulin and prevent life-threatening DKA episodes that otherwise frequently occur at diagnosis.
“Natural history studies have shown us that once someone has reached the threshold of multiple islet autoantibodies, progression occurs similarly in relatives and those with no family history.”
Knowing who is likely to develop type 1 diabetes will help prevent cases of diabetic ketoacidosis (DKA) that occurs when the body doesn’t have enough insulin to allow blood sugar into the cells for use as energy.
Instead, the liver breaks down fat for fuel, producing acids called ketones; the build-up of these ketones to dangerous levels causes DKA.
These episodes can be dangerous and even fatal, causing a number of uncomfortable symptoms. The symptoms of DKA can be the first sign of T1D in people who haven’t yet been diagnosed.
Various research programmes are going on worldwide to establish the best ways of implementing universal screening, including programmes in Germany, the USA, Israel, the UK, and Australia, and a new program (Edent1fi) has just been funded that is going to include multiple new countries in Europe, including the UK, Germany, Poland, Portugal, Italy and the Czech Republic.
Dr Sims noted: “These are all research programs. The next steps before universal screening for type 1 diabetes becomes general policy will require guidelines for monitoring and endorsement of screening and monitoring guidelines by diabetes advocacy societies.”
This will also be helped by broader access to disease modifying therapies to impact progression and the need to start insulin injections.
She explains that these research programmes are in many cases working with primary care doctors to obtain blood testing for autoantibodies – while some of them work through newborn screening (genetic testing performed on infant blood spots followed by antibody screening in individuals at higher genetic risk).
Dr Sims said: “The costs of screening, optimal ways to scale it up, and how to connect it with access to disease modifying therapies, such as the monoclonal anti-CD3 antibody that was recently FDA-approved in the USA for delay of Stage 3 type 1 diabetes in individuals meeting criteria for Stage 2 disease (multiple islet autoantibodies and changes in blood sugar), are all still to be worked out.
“Other important considerations moving forward include reaching traditionally understudied populations and more tailored approaches for individual patients.”
As to the question of when we could see universal screening for T1D rolled, Dr Sims concluded: “I think we will start to see increasing society endorsement of screening and monitoring guidelines over the next five years and that as this occurs, countries will start incorporating screening into routine care for young children at the general practitioner’s office – for example, when children are called for routine childhood vaccinations.”
Screening for adults, who can also develop type 1 diabetes, is less well studied. Although optimal approaches have yet to be clearly elucidated, this population will also likely benefit from identification of early-stage disease and the advantages of education, monitoring, and access to therapy.
Photo by Kane Reinholdtsen on Unsplash