The Glucose Never Lies®
Staging and screening
in Type 1 Diabetes.
The morning Jude’s spot-screen letter arrived, the kettle was on and the kitchen was the usual mid-week mess. The envelope said the newborn screen had picked up islet autoantibodies. We waited a fortnight for the follow-up blood draw. My partner had not been keen on the screen in the first place; I had pushed for it. In the days between the two reads, my own glucose climbed in a way I have learned to read; not the food, not the dose, the waiting. The follow-up came back negative. Jude is fine. The fortnight is what made this page.
If you are sitting with a similar envelope, or with the question of whether to open one at all, this is the page I would have wanted that morning. It is not instructions. It is the shape of what the literature now says, the shape of what the family decision actually feels like, and the shape of where to take the question next. The decision is yours and your diabetes care team’s, in your timing, with your context.
The framework
The staging framework, in plain English.
Type 1 diabetes does not start on the day of clinical diagnosis. It starts months or years earlier, when the immune system begins targeting the insulin-producing cells of the pancreas. By the time a child arrives in clinic with thirst, weight loss, and high glucose, two things have already happened: the immune attack started, and beta-cell function dropped below the threshold that keeps glucose in range. The staging framework names what was happening before that day.
Stage 1 is two or more islet autoantibodies on a normal glucose. The immune signal is there; the metabolic signal is not yet. Stage 2 adds dysglycaemia, abnormal glucose handling on an oral glucose tolerance test (OGTT) or, increasingly, on continuous glucose monitoring (CGM). Stage 3 is the clinical diagnosis many families think of as “the day T1D started”; it is more accurately “the day the underlying disease crossed the threshold of clinical visibility”. The staging framework is a 2015 consensus from JDRF, the American Diabetes Association, and the Endocrine Society (Insel et al, Diabetes Care, 2015) and underpins every stage-routed trial since.
What the framework changes is not the biology. The biology was the same before 2015. What changes is the conversation. A multi-antibody-positive child is not “going to get T1D one day”; they have Stage 1 of a disease that already has a name, a structure, and a research literature attached. The clinic conversation moves from speculative (“we will see”) to anchored (“this is where we are and this is what we watch”).
The autoantibodies that anchor Stage 1 are markers of immune activity against the beta cells, not the immune attack itself. The four most commonly screened are GADA, IA-2A, IAA, and ZnT8A; the screening literature focuses on whether two or more of these are present rather than which specific combination. A single autoantibody, on its own, sits in a different prognostic register from two or more; the multi-antibody threshold is what the staging consensus uses, because it is what the long-follow-up cohorts have shown carries the higher lifetime progression risk. None of this changes the day-to-day life of an antibody-positive child. What it changes is the framework in which their clinical follow-up sits.
Population versus individual
What the population numbers say, and what they do not say.
Across follow-up cohorts of children with two or more islet autoantibodies, around 85 to 90 per cent progress to Stage 3 within 15 years (Insel et al, Diabetes Care, 2015 and subsequent follow-up). The figure describes a population. It does not tell you whether your child progresses next year, in five years, or in fifteen. Population averages mask individual response, and the timing question sits with you and your diabetes care team. A single-antibody result is not zero risk; a multi-antibody result is not a timetable.
Single-antibody positivity is a meaningfully different position from multi-antibody positivity. Single-antibody lifetime progression risk is lower than multi-antibody lifetime progression risk by about an order of magnitude in long-follow-up cohorts. The screening literature focuses on multi-antibody positivity because that is where the higher-risk substrate sits. Neither figure is zero in the tails.
Multi-antibody positivity does not give a date. The progression-to-Stage 3 curve is variable across years; named at population level, lived at individual level. The clinical conversation is about cadence of follow-up, not about a countdown. The first job of any genuine screening conversation is to keep that distinction visible: the population number anchors what is known; the family anchors what happens next.
Two failure modes
Two failure modes worth naming.
Two failure modes flag in this space, and a page that pretends they do not exist is a page that has chosen to comfort rather than to inform.
A single-antibody result is read as “low risk”. The family disengages from follow-up. Years later, the multi-antibody trajectory reveals itself, sometimes in DKA. The single-antibody result was real and the lower lifetime progression risk was real; the failure was in stopping the cadence of conversation with the care team. Neither figure is zero in the tails.
A multi-antibody result lands in a household without the care team in the loop. One parent is ready to act, the other is not. The result becomes a verdict before it becomes a conversation. The household stress that follows is not an inevitable cost of screening; it is the cost of a screening result delivered without the conversation that should have come with it. This is the failure mode the founding moment of GNL turns on.
The fortnight between Jude’s positive newborn spot screen and the negative follow-up blood draw is the lived shape of the false-alarm failure mode, even though Jude’s follow-up came back negative. My partner was not keen on the screen; I had pushed for it; the wait between reads put pressure on a household that already had a clinician-parent in it. The negative result was a relief. The fortnight was real.
If you are reading this with a positive envelope on the kitchen table, the only thing I will tell you is to talk to your diabetes care team. The page is information; the decision is yours and theirs, in your timing, with your context.
Where you can be screened
Where you can be screened, depending on where you live.
European general-population screening sits under EDENT1FI (Hoffmann et al, 2025, master protocol), a coordinated framework designed to bring screening into routine paediatric pathways across multiple countries. UK paediatric screening is structured by ISPAD 2024 Chapter 2 and the ISPAD 2025 paediatric screening recommendations. The operational pathways your family might encounter, depending on country and region, include the following.
Fr1da (Bavaria), the longest-running general-population screening programme for autoantibodies in young children, embedded in routine paediatric care. ELSA UK, the NHS-supported general-population screening study currently active in parts of England. TrialNet, available to first-degree relatives of someone with T1D in the United States, the United Kingdom, and a number of other countries. T1DETECT in the US, the JDRF-supported general-population pathway. EDENT1FI as the European harmonising framework.
Each of these pathways exists at a different stage of integration with routine care. Fr1da is the longest-running, embedded in Bavarian paediatric practice for over a decade, which is why it is referenced so often in the screening literature. ELSA UK is more recent and currently study-enrolment rather than a routine offer; the access route is via the study rather than the GP letter. TrialNet is open to first-degree relatives globally where local sites are active. T1DETECT is a JDRF-supported postal-kit pathway that brought general-population screening within practical reach for many US families. EDENT1FI is the harmonising European framework that several national programmes are now aligning to.
The page is not in a position to tell you which pathway is right for your family; access varies by country, region, and family history. Your diabetes care team will know your local pathway. Asking them, in your own time, is the first conversation worth having.
Care-team referral. Local pathway access is the conversation to have with your family’s diabetes care team. The page is information; the route into screening is theirs to walk you through.
CGM and Stage 2
CGM as a Stage 2 surveillance tool.
CGM is emerging as a Stage 2 surveillance tool alongside OGTT (Desouter et al, Diabetes Care, 2025, n=34 multi-autoantibody-positive first-degree relatives). The signal is real: a longitudinal CGM record adds to OGTT in identifying movement towards Stage 3, picking up patterns of post-prandial drift and slowly rising overnight numbers that an annual OGTT can miss. The optimal CGM metrics for Stage 2 surveillance and the cohort generalisability are still open methodological questions; the cohort was 34 multi-antibody-positive first-degree relatives, not a general-population screening cohort.
This matters because the practical question for a family with a multi-antibody-positive child shifts from “when do we test next?” to “what does month-by-month look like?”. An OGTT is a snapshot. CGM is a film. A film does not replace a snapshot, but it adds something the snapshot cannot. The clinical conversation about whether CGM surveillance is appropriate, available, and the right cadence for your family is, again, with your diabetes care team. The literature is moving; the local pathway is what determines whether the literature reaches you.
Care-team referral. Whether CGM surveillance is in scope for your family, and at what cadence, is a conversation with your diabetes care team. Local availability and clinical fit are theirs to walk you through.
What comes next
What “what comes next” actually looks like.
If a screening conversation produces a Stage 2 result, the question of “what comes next” is the question every family asks. The honest version of the answer is: it depends on the staging, the local pathway, and what is currently licensed where you live. In the United States, teplizumab is licensed for delaying Stage 3 onset in eligible Stage 2 individuals. The depth on what “delay” means, what the eligibility criteria look like, and what the family conversation around it actually involves lives on Part 2 of this cluster (/immunotherapy-t1d/). The word “delay” is doing a lot of work; it is not “prevent” and it is not “cure”.
Disease-modification work using off-patent calcium channel blockade (verapamil; Forlenza et al, JAMA, 2023, CLVer) and TNF-alpha blockade (golimumab; Quattrin et al, NEJM, 2020, T1GER) sits on the exploratory side of the pipeline. Neither is licensed for T1D prevention or cure.
A screening pathway only delivers value if the downstream care chain is in place. Maines et al (2025) frame this as a health-system readiness question, separate from whether screening is technically feasible. For an individual family, this is not a reason to delay a conversation with the care team; it is the structural truth that conditions what options actually reach you when you arrive in clinic.
On the way to clinic
Things worth knowing on the way to your appointment.
If you are reading this page after a positive screening result, a few things worth knowing on the way to your care-team appointment. Whether the result is single-antibody or multi-antibody changes the conversation. Whether OGTT or CGM staging is in scope changes the conversation. The cadence of local follow-up changes the conversation. Your care team will know your local pathway; ask them, in your own time.
If you are reading this page before deciding whether to screen, talking to your care team about whether your family fits the screening literature is the first conversation worth having. Access varies by country and region (EDENT1FI in Europe, ISPAD-aligned local pathways elsewhere). Partner consent and the household’s capacity to hold a positive result are part of the conversation, not an afterthought. The fortnight between two reads is a real cost. So is the cost of finding out at presentation in DKA. Neither column is zero. The conversation is how a family weighs them.
Grace is an educational tool, not a medical device. Nothing on this page is medical advice. Acting on a screening result, single-antibody, multi-antibody, OGTT abnormality, CGM abnormality, sits with your family’s diabetes care team.
The frontier-medicine close
Until you are in that situation, you are just guessing.
Until you are in that situation you are just guessing. The information on this page is what I would want as a parent making the decision. The actual decision sits with you and your care team, in your timing, with your context.
Grace, the educational tool that anchors this page in the underlying literature, is not a medical device. Nothing on this page replaces the conversation with your diabetes care team. The page is the start of a conversation, not the end of one.
GNL’s posture on this surface is research-frontier-aware, evidence-anchored, family-readable, never over-promising. Population averages get the cohort most of the way; the final twenty per cent is where you and your family live, and no average is ever complete.
Where to read next
The four part pages of this cluster carry the depth on each domain.
Part 2 covers immunotherapy and what “delay” means in practice (/immunotherapy-t1d/).
Part 3 covers beta-cell replacement, the immunosuppression trade-off, and the early-phase n=1 work (/beta-cell-replacement-t1d/).
Part 4 covers next-generation insulins, framed as the parallel track that improves daily life now (/next-generation-insulins-t1d/).
The hub is at /prevention-and-cure/.
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