Prevention, Screening, and the Search for a Cure
What we can do today, what is in trials, and what is not here yet. Read it plainly with Jude, earn your way into the evidence and its grades with Grace, then the full appraisal with John. Hopeful, and honest about the gap.
How we teach: three rules, borrowed from Taleb
You earn each level by showing you understand it, not by scrolling past it. We only teach what we would use on ourselves and the people we love.
Understanding beats memory and luck, so the checks reshuffle every time you retry. A pass means you got it, not that you guessed it. And we teach you to tell a landmark result from a headline.
We give you the scaffolding and get out of your way. Roam where your curiosity leads, go as deep as you want, and ask Grace anything. We will not teach a bird how to fly.
Want to ask which screening pathway runs near you, or what a particular trial result actually means for your family? Ask Grace, then take it to your care team.
One page, three depths
This guide compounds: each layer rests on the one beneath it. Read Jude’s plain version, then pass a short understanding check to open Grace, then another to open John. You can roam freely within a layer; you cannot skip ahead a layer, because the next one would not make sense and you would be standing on a gap.
The whole thing, in plain words
A family sitting in a clinic almost always asks the same question: is there a cure coming? The honest answer is more interesting than yes or no. Type 1 diabetes happens because the body’s own immune system attacks the cells that make insulin. Researchers are working along four roads at once, and it helps to keep them separate in your head.
Road one is finding it early. We can now spot type 1 diabetes before it makes anyone ill, with a simple blood test that looks for the early warning signs the immune system leaves behind. Spotting it early means the family is ready, and far fewer children arrive at hospital seriously unwell.
Road two is slowing it down. There is now a medicine that can delay the day a child needs insulin, on average by a couple of years. It is approved in the United States; it is not yet approved here in the United Kingdom. It buys time. It is not a cure, and nobody is calling it one.
Road three is building new cells. Some research puts new insulin-making cells into a person from the outside. A small number of adults with very difficult, dangerous lows have done remarkably well on this in early trials. It is real, it is hopeful, and it is still early; most of it needs medicines that hold the immune system back for life.
Road four is better insulin. While the other roads continue, the insulin itself keeps getting better, so daily life is easier. That is not a cure either, but it matters every single day.
Here is the honest part, and it is the most important sentence on this page. None of these four roads, on its own, is a cure today. Each one is real, each one is moving, and we will not name a date, because nobody honestly can. Good news that is true is worth more than good news that is loud.
Four roads, all genuinely moving, none yet at the finish line. The top line is drawn open and honest, not as a tick that promises a cure. This is a hopeful field, told without a date attached.
Does this match the life of the person living it? A family wants hope they can trust, not hype they will be let down by. If a headline promises a cure with a date on it, treat the date as the part most likely to be wrong, and ask your team what is actually available where you live.The Pemberton lens, lived recognisability, one of the four GNL appraisal lenses.
The four roads, with the evidence and its grades
Road one: finding it early, the staging map
Type 1 diabetes is now understood as a staged disease, not a bolt from the blue. The consensus framework (Insel 2015, the JDRF / Endocrine Society / ADA scientific statement)1 splits it into three stages. The blood test that finds it early looks for islet autoantibodies, the immune system’s fingerprints.
| Stage | What is happening | Symptoms? | Glucose |
|---|---|---|---|
| Stage 1 | Two or more autoantibodies present | None | Normal |
| Stage 2 | Two or more autoantibodies plus a dysglycaemic glucose test | None yet | Slightly abnormal |
| Stage 3 | Clinical type 1 diabetes, the familiar diagnosis | Yes | Diagnostic; insulin starts |
Why bother finding it early? Because finding it early sharply cuts the chance a child arrives at hospital in diabetic ketoacidosis (DKA), a dangerous emergency. Worldwide, about one in three children (roughly 30%) are in DKA at diagnosis, and for infants under one it approaches 60% (Cherubini 2020, an analysis of around 59,000 newly-diagnosed children across 13 countries).2 In families followed closely because their risk was known in advance, DKA at diagnosis in young children fell to roughly 11 to 15% (the TEDDY follow-up study, Elding-Larsson 2011).3 The mechanism is awareness plus follow-up, not a drug.
Road two: slowing it down, the teplizumab evidence
The medicine that can delay clinical onset is teplizumab, an antibody that calms the part of the immune system attacking the insulin-making cells. In the pivotal trial (TN-10, Herold 2019, 76 high-risk relatives at Stage 2),4 a single 14-day course pushed the median time to a clinical diagnosis from about 24 months to about 48 months; the longer follow-up (Sims 2021) extended that to about 60 versus 27 months, with 50% versus 22% still diabetes-free at follow-up.5 It is approved by the US FDA from age 8 for Stage 2 (since November 2022); it is not yet licensed in the UK or Europe for this use.
A separate question is whether the same medicine helps people who have just been diagnosed (Stage 3), by protecting the cells they still have. The phase 3 PROTECT trial (Ramos 2023, 328 children within six weeks of diagnosis)6 found teplizumab preserved more insulin-making capacity at 78 weeks, but day-to-day measures like HbA1c and insulin dose did not differ. So the benefit there is at the cell level, not yet visible in the clinic numbers. Two different questions, often blurred into one in headlines.
A delay, not a prevention. Both arms still reach a clinical diagnosis (the open circles); teplizumab moves the date out by roughly two years on average. The size of the gift varies between people, and this is a group average, not a personal promise. A
A wider exploratory shelf sits alongside teplizumab: golimumab (T1GER, Quattrin 2020) and the off-patent calcium channel blocker verapamil (CLVer, Forlenza 2023) both preserved more insulin-making capacity in newly-diagnosed children.7 Neither is licensed for type 1 diabetes prevention or cure. They signal that several mechanisms can shift the early trajectory; none of them removes the disease.
Road three: building new cells, read carefully
Beta-cell replacement puts insulin-making cells in from outside. The most clinically advanced result (VX-880 / zimislecel, Reichman 2025, 12 adults with severe, dangerous lows)8 reported that 10 of 12 no longer needed injected insulin at the data cut-off, with HbA1c under 7% and time in range over 70% across the group, all under lifelong immunosuppression. A separate first-in-human result (UP421, Carlsson 2025) kept gene-edited cells alive and working for 12 months without immunosuppression, in a single participant.9 Both are genuinely hopeful. Both carry their qualifiers in the same breath as the result: small numbers, about a year of follow-up, and (for VX-880) the burden of immunosuppression for life.
A landmark and a headline are not the same thing. When a result lands, ask the four questions that keep everyone honest: how many people, for how long, compared to what, and is this a delay, a preservation, or a removal of the disease? “Ten of twelve no longer need insulin” is real and it is also twelve people followed for about a year on lifelong immunosuppression. Both halves are true; print both.The Goldacre lens, evidence-grade discipline, one of the four GNL appraisal lenses.
The landscape, the grades, and the limits
The four-domain map, end to end
The field clusters into four mutually-reinforcing domains, and keeping them separate is most of the work of reading it honestly. Domain 1, screening and staging: find pre-symptomatic disease and reduce DKA at diagnosis. Domain 2, disease modification: slow the immune attack (teplizumab, the only approved agent; golimumab, verapamil and a wider shelf in trials). Domain 3, beta-cell replacement: give people new cells (stem-cell-derived islets under immunosuppression; gene-edited or encapsulated cells trying to remove that burden). Domain 4, next-generation insulins: better chemistry while the rest develops (once-weekly basal icodec in the regulatory pipeline; glucose-responsive smart insulins early-phase). None of the four, alone, is a cure.
Where each domain actually sits, by evidence grade
| Domain | Leading evidence | What it shows | Grade |
|---|---|---|---|
| Screening & staging | Insel 2015; ISPAD 2024 Ch 2; Cherubini 2020; Elding-Larsson 2011 | Staged disease; DKA at diagnosis largely preventable through awareness + follow-up | A to C |
| Disease modification | Herold 2019, Sims 2021, Ramos 2023, Quattrin 2020, Forlenza 2023 | Delay of Stage 3 (approved); C-peptide preservation at diagnosis (in trials) | A |
| Beta-cell replacement | Reichman 2025 (VX-880) | Insulin independence in some, under immunosuppression, n=12, ~1yr | B |
| Beta-cell replacement (no immunosuppression) | Carlsson 2025 (UP421) | Proof of mechanism; cells alive and working at 52 weeks | C (n=1) |
| Next-gen insulins | Russell-Jones 2023 (ONWARDS 6, icodec) | Once-weekly basal; not a cure track | A |
A consistent randomised trials. B single early-phase trial or strong cohort. C first-in-human, n=1, or foundational taxonomy. D editorial or working analysis. The grade is part of the claim, not a footnote to it.
“Cure” is not the right word for a delay, a preservation of C-peptide, or a replacement under chronic immunosuppression. Each agent gets the word the evidence supports. The day-after-tomorrow promise, with a year on it, is the single most reliable marker of a story that has crossed from evidence into hype.
The honest paragraph, and why we will not name a date
Grace’s depth on day-to-day type 1 diabetes is a Grade B real-world evidence base. Her cure-research depth is best described as a credible early build: the foundational papers are in, the four-domain map is structured, and the work to bring it to parity is the next year of building. We will not name a years-to-cure number, because the literature does not support one and quoting one creates harm. Several agents have shown promise in trials over the past five years; the gap from a trial result to a treatment that arrives in clinic is real, and it varies by domain. Clarity by subtraction (the Via Negativa principle that runs through every GNL surface) applies hardest here: we remove the false certainty rather than add a comforting one.
The asymmetry is the whole point. A delay that buys a child two years before pump and CGM is a real, bankable gain with a known, manageable downside. A cell therapy that needs lifelong immunosuppression carries a small chance of a large, irreversible harm; that tail is exactly what a young, well-controlled person cannot afford to ignore. Weigh the rare catastrophic outcome heavily, not the average trial Tuesday.The Taleb lens, robustness to outliers, one of the four GNL appraisal lenses.
A field is only as honest as its weakest qualifier. UP421 is one participant; VX-880 is twelve, on immunosuppression, at about a year; PROTECT moved a cell-level marker but not the clinic numbers. Name what would strengthen each result (a larger cohort, longer follow-up, an immunosuppression-free route that scales) and never let a proof of mechanism be sold as a therapy. Durability in type 1 diabetes is answered in decades, not in a press release.The Hayes lens, technical and methodological rigour, one of the four GNL appraisal lenses.
The whole guide, summarised
Glucose never lies, and neither will we about where the science actually stands. Good news that is true is worth more than good news that is loud.
Read your own staging picture
This is a teaching tool that translates a screening result into the staging language clinicians use. Enter how many islet autoantibodies were found, whether a glucose test (OGTT) was normal or dysglycaemic, and whether there are symptoms. It tells you which stage the picture maps to and what the next conversation usually is. It is education only, not a diagnosis, and not a substitute for the screening service that interprets the actual bloods.
No values are pre-filled; you enter every value fresh. This maps to the published staging framework (Insel 2015; ISPAD 2024); it does not read your actual bloods and it is not a diagnosis. Screening identifies; it does not commit anyone to any medicine. Confirm anything here with your GP, paediatrician, or screening service. If symptoms of diabetes are present, that is an urgent same-day medical question, not a teaching tool.
This page is the taster. The full journey, three modules and their questions, with your progress saved, lives in Learn with Grace. Glucose never lies; come and learn to read the science honestly.
References
Evidence grades A (strongest) to D (editorial or working analysis). The grade is part of the claim.
- Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964-1974. C (foundational taxonomy)
- Cherubini V, Grimsmann JM, Akesson K, et al. Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 2020;63(8):1530-1541. A
- Elding Larsson H, Vehik K, Bell R, et al; TEDDY Study Group. Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up. Diabetes Care. 2011;34(11):2347-2352. B
- Herold KC, Bundy BN, Long SA, et al; Type 1 Diabetes TrialNet Study Group. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 2019;381(7):603-613. Median time to clinical T1D 48.4 vs 24.4 months (HR 0.41, 95% CI 0.22 to 0.78). FDA approval of Tzield, November 2022. A
- Sims EK, Bundy BN, Stier K, et al. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021;13(583):eabc8980. Extended follow-up 59.6 vs 27.1 months; 50% vs 22% diabetes-free. A
- Ramos EL, Dayan CM, Chatenoud L, et al; PROTECT Study Group. Teplizumab and beta-cell function in newly diagnosed type 1 diabetes. N Engl J Med. 2023;389(23):2151-2161. Phase 3, 328 children; higher week-78 stimulated C-peptide with teplizumab (p<0.001); HbA1c, insulin dose, time in range not significantly different. A
- Quattrin T, et al. Golimumab and beta-cell function in youth with new-onset type 1 diabetes (T1GER). N Engl J Med. 2020;383(21):2007-2017; and Forlenza GP, et al. Effect of verapamil on pancreatic beta-cell function in newly diagnosed pediatric type 1 diabetes (CLVer). JAMA. 2023;329(12):990-999. A
- Reichman TW, et al. Stem cell-derived, fully differentiated islets for type 1 diabetes (VX-880 / zimislecel). N Engl J Med. 2025. Phase 1/2, 12 adults; 10 of 12 insulin-independent at data cut-off under chronic immunosuppression. Phase 3 under way. B
- Carlsson P-O, et al. Survival of transplanted allogeneic beta cells with no immunosuppression (UP421). N Engl J Med. 2025. First-in-human, single participant; cells alive and glucose-responsive at 52 weeks without immunosuppression. C (n=1, proof of mechanism)
- Russell-Jones D, et al. Once-weekly insulin icodec in type 1 diabetes (ONWARDS 6). Lancet. 2023. Next-generation basal insulin; not a cure track. A
One page, three voices: Jude, Grace, John. Research-aware, evidence-anchored, no date attached.