• Researchers outlined guidance for healthcare systems to establish general population type 1 diabetes screening.
• The consensus report details suggestions for discussing screening and results with families.

A new consensus guideline advocates for healthcare systems to conduct general population screening for type 1 diabetes.

In an article published in Diabetologia, an international group of experts detailed recommendations for conducting general population screening for type 1 diabetes islet autoantibodies to diagnose early-stage disease. The report, which was endorsed by 20 diabetes organizations from around the world, detailed the age and frequency at which screening should take place, how healthcare professionals should discuss screening and results with families and the steps countries should take when implementing a general population screening program.

Anastasia Albanese-O’Neill, PhD, ARNP, CDCES, senior vice president of medical affairs at Breakthrough T1D, an author on the consensus guideline and a Healio | Endocrine Today Editorial Board Member, described general population screening for type 1 diabetes as a meaningful leap forward for detecting and treating the condition.

“We know we have some distance to go, but there is a lot of evidence to support the benefits of screening to detect early-stage type 1 diabetes,” Albanese-O’Neill told Healio. “It’s an exciting time. Screening and monitoring together have been shown to prevent diabetic ketoacidosis at diagnosis. Screening is how we get people connected to those essential clinical trials. This is how we get people to approved therapies and, one day, to our shared dream of preventing type 1 diabetes.”

Healio spoke with Albanese-O’Neill about why the authors decided to recommend general population screening, some of the barriers healthcare systems need to overcome to implement wider screening and what are currently some of the biggest gaps in evidence.

Healio: Why was it so important to publish this consensus guidance on general population screening for type 1 diabetes?

Albanese-O’Neill: Early detection of type 1 diabetes before symptoms appear and before insulin is required can help reduce the life-threatening risk of diabetic ketoacidosis at diagnosis. We have evidence of this meaningful clinical benefit from decades of research on type 1 diabetes screening and follow-up monitoring. It gives people time to access therapies and make decisions with their doctor about disease-modifying therapies. They can also choose to participate in crucial clinical trials and prepare for their future medical needs with what we hope is a softer landing.

We are at a pivotal moment in type 1 diabetes care where we are no longer focusing solely on treating the metabolic consequences of a type 1 diabetes diagnosis. We’re thinking about the potential to target the underlying autoimmune causes of the disease. This is an inflection point. It’s been the goal of decades of our research investment at Breakthrough T1D, the NIH and other funding agencies as we seek to slow down, halt and eventually prevent the immune attack on the insulin-producing cells in the pancreas.

Healio: How would you define the take-home message of this consensus guidance?

Albanese-O’Neill: We’re at this pivotal moment in type 1 diabetes care. If we limit screening to family members, we will miss 85% to 90% of people who will go on to develop a type 1 diabetes diagnosis. Most people diagnosed with type 1 diabetes do not have a family history.

The first two recommendations in the paper are important take-homes. The paper doesn’t say to just start screening tomorrow. The first recommendation clearly notes that where policy and infrastructure is in place, we should offer general population screening, and this means that not every country is at the same point in the process. Each geography will need to build that supporting infrastructure and policy.

We are one step in that direction in the U.S. with the American Diabetes Association’s recommendation to screen family members and people with otherwise known elevated genetic risk. That second recommendation in the paper points to targeted screening and monitoring of individuals who are at increased risk as a natural starting point to build essential infrastructure.

The last key recommendation in this section says that prior to screening people for early-stage type 1 diabetes, you need to figure out how you are going to confirm positive results, how are you going to monitor people, and how you are going to refer them so they can realize those benefits we talked about.

Healio: What barriers may prevent general population screening for type 1 diabetes and how can these barriers be overcome?

Albanese-O’Neill: The importance of this paper is that international experts have developed a common framework for how general population screening for type 1 diabetes can be implemented in clinical practice. The specific design of each screening program in each region will need to be adapted to that respective healthcare system and, where possible, linked to programs that are already in place.

The two key challenges are policy and clinical infrastructure. The starting point is building the monitoring infrastructure, that is job No. 1. Then you need to, with a more limited population, think about clinical or public health pathways to screen people already recommended in local guidelines. For example, in the U.S., we have only screened a small fraction of people who are family members of people with type 1 diabetes or people who have otherwise known elevated genetic risk, like a personal or family history of autoimmune thyroiditis, celiac disease, etc. We should start there. We also need community awareness about this, and we need reimbursement for these activities.

Healio: What are some of the potential harms of general population type 1 diabetes screening and how can they be addressed?

Albanese-O’Neill: One of the harms that we identified is blood sampling, as it can be painful or cause bruising. This can be mitigated by recruiting and training healthcare professionals on best practices. For example, we can use topical anesthetics with children or utilize devices like the Buzzy Bee that reduce pain. There are ways we can mitigate that specific, narrowly targeted harm.

We know that there is a psychological impact of participating in any kind of screening program, and in this case, specifically knowing about early-stage type 1 diabetes may cause some anxiety. We know, at least initially, that this anxiety can often be mitigated with education and support over time with participation in a monitoring program. Some people may experience more than the expected grief response, and in these cases, we can refer to a partner in behavioral health with expertise in early-stage type 1 diabetes.

In any screening program, people can receive false-positive or false-negative test results. There’s a number of recommendations in the paper about how to reduce these risks. There is also a strong emphasis on confirmatory testing to be certain the individual has persistent autoantibodies and should be diagnosed with type 1 diabetes.

We also don’t want to give false reassurance when somebody screens and autoantibodies are not detected. We can never tell someone they or their child will never progress to type 1 diabetes. If a child screens negative all three time points recommended in the paper at age 2 to 4 years, 6 to 8 years and 10 to 15 years, while it is unlikely that your child will progress to a type 1 diabetes diagnosis, the likelihood is not zero.

There’s also concern about stigma, and we need to continue with community education. Not just for type 1 diabetes, but for all chronic conditions, we need to promote education, acceptance and reduce stigma.

Healio: The guidance provides details on how to discuss screening results with families. What are some of the key takeaways from this section?

Albanese-O’Neill: The recommendations include using clear and neutral terminology. We already talk about that a lot in type 1 diabetes clinical care. The goal is to avoid words like “good” or “bad,” such as saying, “That is a bad blood sugar.” The same thing applies here. Clear, neutral terminology should be used while providing the test result.

It is important to avoid language that creates avoidable anxiety. The screening result is not a diagnosis. We must clearly communicate the need for confirmatory testing for a diagnosis. Communication should be calm, clear and factual.

We want to make sure that a personal phone call is offered and that the communications isn’t just a release of the results into the electronic health record. People should be able to talk to someone about the results, obtain a clear explanation and get their questions answered. Some people may feel relief if autoantibodies are not detected. Some people may feel anxiety. We don’t know how any one person will feel, but they’re going to have a reaction to these results one way or the other, and healthcare professionals need to be ready for that. A plan of care for what comes next must also be communicated.

Healio: How much have you learned from a country like Italy that is already starting general population screening and how much of that can be extrapolated to other countries?

Albanese-O’Neill: We know that DKA was reduced in Italy. That is a clear win. We know that parents responded well for the most part to having their children screened. We need to learn from the Italian experience in how it worked and what we can reproduce in other geographies. In general, we need more in the literature on best practices in screening to detect early stage type 1 diabetes.

I would urge the clinical community, if they have set up an early type 1 diabetes clinic in the U.S., to publish their findings in the scientific literature. Let’s not reinvent the wheel one clinic at a time. We can all learn from each other. Established programs like Italy will lead the way. They were at the forefront.

Healio: What are some of the biggest gaps in evidence on this topic and what further research is needed moving forward?

Albanese-O’Neill: The biggest gap is among adults. The writing group could not make a strong recommendation around adults; we need to build more evidence.

We need more evidence for how predictive a single autoantibody is in adults. We need evidence about people with single autoantibodies, especially in the general population.

We also need a standardized model for clinical care for people with early-stage type 1 diabetes. Again, I want to urge the clinical community to publish research on effective clinical implementation of monitoring. Guidance has been out for about 2.5 years, so this is an opportunity to start hearing from clinical teams about efficacy, patient satisfaction, provider satisfaction, reimbursement and, of course, patient outcomes.

Anastasia Albanese-O’Neill, PhD, ARNP, CDCES, can be reached at aaoneill@breakthroughT1D.org or LinkedIn @albaneseoneill.