Staging and Screening: Finding T1D Before the Diagnosis

The screening question, in our family

The question came up because Jude is mine, and I have T1D. The risk for a child of someone with T1D is small in absolute terms but real, and the modern screening pathway means you can ask the question early and get an answer in capillary blood. I wanted to know. Danielle did not, and her reasons were good ones. There is no medicine to start at Stage 1, and a positive result lives with the family for as long as it takes the science to catch up. We talked about it for weeks before we did it.

What I had not anticipated, and what surprised me most, was what the waiting did to me physically. The two of us had quietly settled on the assumption that the result would be positive. That assumption is not how the statistics work, but it is how a parent’s mind works, and once it lodges it does not let go until the envelope arrives. My continuous glucose trace through those days reads like a small uphill ramp that will not flatten with my usual moves. Stress hormones are real; I knew that as a clinician and as someone who has lived with T1D for years. I had not felt it land that hard in my own body until I sat with it as a parent waiting for a child’s bloods.

The result came back negative. We breathed. The waiting changed how I think about diabetes management, and especially about what the parents I work with at clinic carry that they rarely say out loud. The dread of an unknown is its own physiological event. The move from negative-thought-cycling to a more realistic state is real work, and worth naming. The screening did not commit us to anything; it gave us information, and the information, as it turned out, was what let us move on. The family gets to choose what to do with the information; the science just brings it within reach earlier than it used to be.

Stage 1, Stage 2, Stage 3, in plain English

What the science calls “screening” is not a test for diabetes in the textbook sense. It is a blood test for the antibodies the immune system makes when it has started to attack the insulin-producing cells in the pancreas. The attack happens silently for years before the body’s blood glucose starts to misbehave; by the time anyone is in clinic with classical symptoms, the autoimmune process has been running, in many cases, for the best part of a decade. The staging framework agreed in 2015 (Insel and colleagues, Diabetes Care) gave the field a shared way of speaking about that hidden run-up, and every modern T1D prevention conversation now routes through it.

Stage 1 is the immune system already attacking, with two or more autoantibodies in the blood, but the child still has normal glucose tolerance and no symptoms. Stage 2 is the same process now visible on a glucose challenge, with two or more antibodies and a dysglycaemic response on an oral glucose tolerance test (or a rising HbA1c, or impaired fasting glucose), still without clinical symptoms. Stage 3 is the clinical T1D the family already recognises, with symptoms, the diagnosis, and the start of insulin therapy. The framework is now embedded in international paediatric guidance (Haller and ISPAD, 2024).

The reason the staging matters in plain English is that progression is not a maybe but a when. The published cohort data summarised in the Insel statement put the lifetime risk of progression to clinical T1D in someone with two or more antibodies at around eighty-four percent over fifteen to twenty years. The 2024 ISPAD update sharpened the figure: among children at Stage 1, around forty-four percent progress to Stage 3 within five years and eighty to ninety percent within fifteen; among children at Stage 2, three quarters progress within five years and nearly all do during their lifetime. Knowing that earlier does not change what is happening in the pancreas; it changes the family’s window to plan, the diabetes team’s window to prepare, and (where licensed) the conversation about an immune-modifying medicine that can shift the timing.

How screening pathways work in different countries

The route into a screening conversation depends on where the family lives and which research network the local paediatric diabetes service is connected to. None of the modern pathways exists on every street corner; together, they have moved population autoantibody screening from a research idea to an active clinical infrastructure across at least eight European countries and parts of the United States. The largest current programme is the European action for the Diagnosis of Early Non-clinical Type 1 diabetes For disease Interception, EDENT1FI (Hoffmann 2025, BMJ Open): a coordinated public-health screening framework targeting two hundred thousand European children aged one to seventeen by 2028, with the United Kingdom among the participating countries. By March 2025, EDENT1FI had screened one hundred thousand children at a steady run rate of around six thousand five hundred per month, with roughly 0.36 percent confirmed positive for multiple islet antibodies on venous follow-up.

Around EDENT1FI sit the older national programmes it builds on. In the United States, TrialNet has run since the early 2000s as a free relative-based screen for first-degree and second-degree relatives of people with T1D, with TEDDY following a HLA-screened birth cohort with longitudinal antibody and OGTT testing. In the United Kingdom, ELSA (Early Surveillance for Autoimmune Diabetes) screens children aged three to thirteen through a partnership between the diabetes charity sector and the NHS. In Germany, Fr1da has run general-population screening at well-child visits in Bavaria since 2015 (this is the programme on which the EDENT1FI design is based). In the United States again, T1DETECT is a JDRF / Breakthrough T1D home-test mailing programme that lets families request a finger-prick antibody kit by post.

What changes between programmes is who gets offered the test, which antibodies are measured, and what happens next. What does not change is the underlying question. Screening alone does not commit anyone to anything: a positive result opens a conversation about surveillance and (where licensed) about disease-modifying therapy. The decision to screen is one decision; the decisions that follow a result are separate, and the family enters or declines each one on its own terms. The honest framing is that the field’s evidence has moved faster than population access has. Many family encounters about Stage 1 or Stage 2 are with clinicians who are themselves still learning the framework, and many countries (the UK included) do not yet have a licensed Stage-2 therapy. That is not a reason to delay the conversation; it is a reason to know what you are walking into before you decide.

What CGM adds to Stage 2 surveillance

The original Stage 2 surveillance pathway was built around the oral glucose tolerance test. The OGTT is logistically expensive (a fasting morning, a clinic visit, repeat blood draws over two hours), the child has to drink a sugary load, and the test catches a single moment in the body’s glucose handling. For a young child being followed across years, every OGTT is a real event. Continuous glucose monitoring offered an obvious-on-paper alternative, but the question was whether a CGM-based surveillance pathway would actually catch the same transitions the OGTT was catching, especially the clinically important shift from Stage 2 to Stage 3.

The first proper head-to-head answer landed in 2025. Desouter and colleagues (Diabetes Care) followed thirty-four multiple-antibody-positive first-degree relatives across multiple years with repeated CGM wear, repeated OGTT, and HbA1c. CGM metrics performed comparably to repeated OGTT for predicting progression to clinical T1D; HbA1c performed less well than either, and missed transitions that CGM picked up. The cohort was small and replication is needed in larger multi-site work, but the practical implication is real: a continuous wearable can do most of the surveillance work the clinic-based test was doing, with the test reserved for moments when the wearable signal needs confirming.

What that means in clinic is a Stage 2 follow-up that looks more like ordinary T1D care than ordinary clinic surveillance. The family wears a sensor, the team watches the trace, the child gets fewer hospital visits and fewer fasting mornings. The OGTT does not disappear; it earns its place when the CGM signal raises a question, rather than as the routine clock. Where the family lives, what their team has access to, and which research network the local service is part of will all shape what is actually offered.

What families can take to the team

If a sibling, child, parent, or close relative has T1D and the family is wondering about screening, that question is now a real one and the team is ready for it. UK families can ask about ELSA and about whether the local paediatric diabetes service is connected to EDENT1FI. US families can ask their paediatric endocrinology service about TrialNet, or order a T1DETECT kit by post. Bavarian families come into Fr1da at the well-child visit. If a screen has already returned at Stage 1 or Stage 2, the next conversation is with a specialist paediatric diabetes service that has experience with the staging framework and with ongoing surveillance. In countries where teplizumab is licensed, the Stage 2 conversation includes whether to pursue evaluation; in countries where it is not, the conversation is about close monitoring, family education, and trial pathways where they exist.

The honest part of all of this is that information identifies, the family decides, the team supports. The conversation has moved faster than access in many places, and what feels obvious on paper (screen everyone, treat everyone) is not what families actually meet at the kitchen table. Some families want the information and use it to plan; some want a different relationship with the unknown. Both readings are reasonable. What the science offers is a way to ask the question earlier than the body would otherwise force; what the family does with the answer is the family’s choice. The diabetes team’s job is to make the options legible and to walk the family through what each one looks like, including the watching-and-waiting option, with no pressure to take any of them on a clock the family has not chosen.

References for this part