For most of its history, type 1 diabetes (T1D) has been diagnosed late. By the time symptoms appear, the autoimmune destruction of pancreatic beta cells has usually been underway for years, with a substantial proportion of insulin-producing capacity already lost. The consequences of this late diagnosis are familiar: diabetic ketoacidosis (DKA), emergency hospital admissions, and an abrupt, often traumatic transition into lifelong insulin dependence.
Screening the general population for T1D is an attempt to change that trajectory. Instead of waiting for hyperglycaemia and symptoms, screening aims to identify the disease while it is still silent — during the autoimmune stages that precede clinical diabetes. For a long time, this idea sat uncomfortably in public health. Identifying risk without the ability to intervene risks turning healthy people into patients-in-waiting, burdened with anxiety but offered little in return. There was no systemic way to support families that had children displaying autoantibodies, unless those were contained within families where type 1 was already present. Even then, it presented an ambiguous risk. When would a single antibody lead to dysglycaemia and ultimately, Type 1 diabetes?
That objection is now becoming increasingly difficult to sustain.
With the emergence of national screening programmes (most notably in Italy), the approval of disease-modifying immunotherapies, the rise of genetic-first initiatives such as T1D Scout, and growing evidence that beta-cell loss may be slowed or altered by immunomodulatory cell therapy, screening is no longer just about early warning. It is increasingly becoming the front door to treatment, and potentially the foundation for a very different model of T1D care.
What Does Screening for Type 1 Diabetes Actually Mean?
Screening for T1D is often described as if it were a single test. In reality, it is better understood as a layered process, with each layer answering a different biological question.
Genetic screening: who is at risk?
At the broadest level sits genetic risk screening. Certain genetic variants — particularly in the HLA region — confer increased lifetime risk of developing T1D. About 90% of people with T1D carry specific HLA haplotypes, compared with roughly half of the general population. However, genetics alone is a blunt tool. Many people with high-risk genotypes never develop diabetes, while others with modest genetic risk do.
Early genetic screening strategies therefore struggled with poor specificity. Broad HLA-based approaches could capture most future T1D cases, but at the cost of labelling very large numbers of people as “at risk,” most of whom would never progress. This was one reason population-level genetic screening for T1D was historically viewed as impractical.
That picture has changed with the development of polygenic risk scores. Instead of focusing on a handful of genes, modern scores combine dozens of genetic variants into a single risk estimate. One widely cited example, the Type 1 Diabetes Genetic Risk Score 2 (T1D-GRS2), integrates 67 variants and has demonstrated strong discrimination between people who will and will not develop T1D, outperforming HLA-only approaches and significantly improving screening efficiency
(https://link.springer.com/article/10.1007/s00125-023-05955-y).
Large prospective studies have shown how this can work in practice. The TEDDY study used genetic screening at birth to identify infants at elevated risk and followed them longitudinally to understand how autoimmunity develops
(https://teddy.epi.usf.edu/).
In Europe, the Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has gone further, implementing newborn genetic screening at population scale. Using a refined genetic risk algorithm, GPPAD identifies roughly 1% of infants with a markedly elevated risk of developing early islet autoimmunity and invites them into structured follow-up and prevention trials
(https://www.gppad.org/).
The key point is that genetics does not diagnose disease. It answers a different question: who is worth watching closely? Genetics is stable over life, requires only one test, and allows screening programmes to focus resources where they are most likely to matter.
This logic underpins consumer-facing models such as T1D Scout, which use low-friction at-home genetic testing as a first pass, followed by targeted autoantibody testing only in those with elevated genetic risk. Genetics becomes a filter, not a label.
Autoantibody screening: has disease begun?
The transition from risk to disease is marked by the appearance of islet autoantibodies. These antibodies — typically against insulin, GAD65, IA-2, and ZnT8 — reflect active autoimmune attack on beta cells and can appear years before glucose levels rise.
The presence of:
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one autoantibody signals increased risk
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two or more autoantibodies defines Stage 1 T1D, with a high lifetime probability of progression
At this point, T1D is no longer hypothetical. Autoimmunity is active, even if the person is asymptomatic.
Autoantibody screening is therefore the diagnostic core of presymptomatic T1D detection. Genetics determines who gets tested; antibodies determine whether disease has started.
Metabolic staging: how far has it progressed?
Once autoimmunity is established, glucose testing — via OGTT, HbA1c, or increasingly CGM — is used to stage disease progression:
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Stage 1: normoglycaemia
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Stage 2: dysglycaemia
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Stage 3: clinical diabetes
This staging now matters clinically, because intervention eligibility increasingly depends on it.
Does Screening Work?
The most immediate and robust benefit of screening is the prevention of DKA at diagnosis. Across multiple studies, children identified through screening enter care earlier and more gently, with DKA rates falling from 20–40% in unscreened populations to low single digits.
Screening also leads to earlier diagnosis, lower HbA1c at onset, greater residual C-peptide, and smoother transitions onto insulin therapy. For years, these benefits were viewed as secondary. That calculus is changing as therapies emerge that require preserved beta-cell function to work at all.
When Screening Succeeds — and When It Fails
History shows that screening programmes succeed or fail for predictable reasons.
Screening works when early detection is tightly coupled to decisive action that prevents harm. Newborn screening for phenylketonuria (PKU) is the archetypal success: early detection followed by immediate dietary intervention prevents irreversible neurological damage. This is why PKU screening is formally recommended and embedded in national programmes
(https://view-health-screening-recommendations.service.gov.uk/pku/;
https://www.phgfoundation.org/wp-content/uploads/2023/10/Expanded-newborn-screening-a-review-of-the-evidence.pdf).
Cervical cancer screening follows the same logic. Detection of a long presymptomatic phase, combined with effective treatment pathways, reduces cancer incidence and mortality
(https://www.gov.uk/topic/population-screening-programmes/cervical).
Screening fails when detection outpaces resolution. PSA-based prostate cancer screening increased early cancer detection but led to widespread overdiagnosis and overtreatment, with modest or uncertain mortality benefit
(https://www.bmj.com/content/362/bmj.k3519;
https://www.iqwig.de/en/presse/press-releases/press-releases-detailpage_9949.html).
The lesson is not that screening is dangerous, but that screening without risk stratification and proportionate response erodes trust.
T1D screening has historically suffered from this gap. Identifying Stage 1 disease often led only to monitoring. Preventing DKA is valuable, but less intuitively compelling than preventing cancer or neurological injury when years of uncertainty may follow.
What is changing is the narrowing gap between detection and action.
Italy: Screening as Infrastructure
Italy’s decision to mandate nationwide screening for T1D and coeliac disease marks a shift from pilot science to public-health infrastructure. Autoantibody testing is integrated into routine paediatric care. Public health screening programmes in Europe (most notably the Fr1da study in Bavaria) have found that approximately 0.3 % of general population children screen positive for multiple islet autoantibodies, indicating presymptomatic type 1 diabetes — children who would otherwise remain invisible until diagnosis.
Crucially, Italy’s programme is framed not as passive surveillance, but as preparation: for early diagnosis, education, DKA prevention, and the deployment of disease-modifying therapies as they become available.
Italy is betting that detection infrastructure must come before therapeutic certainty.
What Happens After a Positive Screen — Today
At present, a positive screen leads to confirmatory testing, staging, education, and regular monitoring. For individuals in Stage 2 T1D, immunomodulatory therapy has now demonstrated the ability to delay progression to insulin-dependent diabetes, changing the ethical calculus of screening by offering tangible benefit.
Screening is no longer just informational, however, treatments that are available and approved are not inexpensive, and only provide respite for 2-3 years.
Looking Ahead: From Immune Suppression to Beta-Cell Preservation
Stage 1 T1D is often described as asymptomatic, but it is not biologically quiet. By the time multiple autoantibodies appear, beta cells are already under immune pressure. Stress pathways are activated, antigen presentation is ongoing, and inflammatory signalling is present even while glucose remains normal.
This opens a more radical possibility: future early intervention may focus not only on suppressing immune attack, but on preserving beta-cell resilience.
Emerging immune-modulating and cell-based therapies aim to dampen autoimmune aggression while simultaneously protecting beta cells from stress-induced dysfunction and death. Early trials of such approaches have shown long term preservation of endogenous insulin secretion, improved metabolic stability, and sustained C-peptide levels — outcomes that were previously thought unattainable once autoimmunity was established
(https://www.nextcellpharma.com/press-releases/six-year-data-demonstrate-a-durable-disease-modifying-effect-of-protrans-in-type-1-diabetes).
The article linked above discusses immune dampening in those with stage three of type 1 diabetes. They showed 60% retention of beta cells after 6 years. But imagine what the effect might be were the treatment initated at stage 1 or stage 2. How many beta cells might be retained? If these approaches continue to mature, it becomes conceivable that early-stage intervention — particularly when guided by genetic risk stratification and autoantibody staging — could dramatically delay, soften, or in some cases prevent progression to clinical T1D. And the effects of managing the immune system in this way are potentially much less of a sledgehammer than treatment with Tepluzimab.
In such a future, genetics no longer simply identifies risk. It licenses early intervention, ensuring therapies are targeted at those most likely to benefit and avoiding the overdiagnosis traps that doomed other screening programmes.
Stage 1 would no longer be a warning label followed by years of watchful waiting. It would become an actionable clinical state.
From Warning Label to Treatment Pathway
Screening for type 1 diabetes is no longer justified because we already have perfect therapies. It is justified because we cannot deploy future therapies without early detection.
Screening becomes infrastructure: preserving therapeutic windows, enabling proportional intervention, and allowing disease course to be shaped rather than simply endured. Italy has chosen to build that infrastructure now. Models such as T1D Scout suggest alternative, decentralised routes to the same goal.
Screening does not cure type 1 diabetes. But without it, many of the most promising interventions will always arrive too late.
That is the shift now underway — from screening as a warning label, to screening as the first step in a treatment pathway that may one day make type 1 diabetes a far rarer diagnosis than it is today.
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