Diabetes In Focus
Early screening for type 1 diabetes may be beneficial
Early screening for type 1 diabetes in children could significantly alter the disease’s course, according to a study in the Journal of the American Medical Association.
Researchers tested more than 220,000 children in Germany, finding that screening should not be limited to those with a family history of diabetes,
as most children who developed the disease did not have a family history.
Hos barn kan ett blodprov långt innan symtomen utvecklas eller en nödsituation uppstår, rapporterade forskare, vilket tyder på att mer utbredd tidig screening kan vara i ordning
Rapport
De flesta barn som utvecklade typ 1-diabetes i denna studie hade ingen familjehistoria av sjukdomen, vilket innebär att screening inte bör begränsas till dem med en familjehistoria, säger forskarna i en rapport i JAMA
”Förmågan att upptäcka typ 1-diabetes tidigt genom screening och övervakning är ett betydande genombrott med stor potential att nå en bred befolkning och ändra sjukdomsförloppet för dem som kommer att utveckla den”, säger Esther Latres från Breakthrough T1D, som hjälpte till att finansiera forskningen, i ett uttalande.
Familjer känner ofta inte igen de tidiga varningssymptomen på diabetes som överdriven törst, viktminskning eller trötthet, vilket leder till utveckling av diabetesketoacidos, en allvarlig medicinsk nödsituation, noterade forskarna.
I studien i Tyskland testades mer än 220.000 barn för tidiga stadier av typ 1-diabetes under rutinmässig pediatrisk vård. Ett litet blodprov analyseras för närvaron av minst två olika typer av islet autoantikroppar, som är immunceller som felaktigt angriper bukspottkörteln.
• Barn med islet autoantikroppar men normala blodsockernivåer anses vara i steg 1. Familjer får information, utbildning och tillgång till specialiserade diabetescenter där regelbundna uppföljningsundersökningar sedan sker.
• I steg 2 uppträder de första tecknen på nedsatt glukosmetabolism
• I steg 3 krävs insulin.
Vid den första screeningen visade sig 590 barn, eller ungefär 0,3%, ha tidig typ 1-diabetes. Så småningom gick 212 av dem vidare till steg 3.
Efter fem år var sannolikheten för att utvecklas från ett tidigt stadium till klinisk typ 1-diabetes 36,2%, rapporterade forskare.
När ett tidigt stadium diagnostiserades fanns det ingen skillnad i sjukdomsprogression hos barn med och utan familjehistoria, noterade de.
”Det långvariga argumentet att tidig sjukdom inte lätt kan identifieras – och därför inte effektivt kan studeras eller riktas – håller inte längre”, säger Dr. Jamie Felton och Dr. Emily Sims från Indiana University School of Medicine, som inte var involverade i studien, skrev i en redaktionell editorial
”Resultaten tyder på att tiden för att allvarligt överväga allmän befolkningsscreening har kommit”, avslutade de.
From Reuters Health
From JAMA Editorial
https://jamanetwork.com/journals/jama/article-abstract/2849407
A New Type 1 Diabetes Diagnosis Paradigm
Jamie L. Felton, MD1; Emily K. Sims, MD1
Published Online: May 21, 2026
doi: 10.1001/jama.2026.6454
Classically, type 1 diabetes has been diagnosed only after patients have lost a critical threshold of beta cell mass, resulting in symptoms of hyperglycemia due to insulin deficiency.1 Despite advances in glycemic monitoring and insulin delivery, patients with clinical type 1 diabetes experience enormous mental burden and health care costs and are at risk of developing complications from chronic hyper or hypoglycemia.1 Natural history studies have shown that type 1 diabetes can be diagnosed in presymptomatic stages via detection of 2 or more islet autoantibodies.2 Stage 1 is defined by the presence of 2 or more islet autoantibodies with normoglycemia and stage 2 by the presence of 2 or more islet autoantibodies and abnormal glucose metabolism. Stage 3 marks the clinical diagnosis of type 1 diabetes, characterized by hyperglycemia.
Options for disease modification to intervene in the presymptomatic stages and delay insulin requirements are becoming available clinically or through prevention trials testing agents shown to have efficacy in stage 3 disease3 (NCT07222137 and NCT07216391). As these advances in prediction and disease modification evolve, the long sought–after possibility of prevention of clinical type 1 diabetes is now approaching reality. With this possibility for intervention, screening for presymptomatic type 1 diabetes begins to meet the criteria for the principles and practice of screening by Wilson and Jungner,4 which state that screening programs should target health conditions that are detectable at an early stage, have an effective intervention when applied early, and have a valid, reliable, and acceptable test available. In addition, Wilson and Junger outline the importance of cost-effectiveness and the existence of intrastructure and systems to support diagnosis, treatment, and follow-up to ensure that benefits outweigh potential harm.4
In this issue of JAMA, Winkler and colleagues5 address a critical question that has been challenging to answer:
What is the frequency and prognosis of early-stage type 1 diabetes in children from the general population? Their findings are simultaneously surprising and reassuring. They not only demonstrate the feasibility of detecting type 1 diabetes in a nontargeted population, but also highlight an efficient and effective system that supports diagnosis, follow-up, and treatment—aligning with the screening principles outlined by Wilson and Junger.4
Most importantly, they compel reconsideration of the practice of limiting screening exclusively to individuals with first-degree relatives with type 1 diabetes or based on known genetic risk. Several key ideas emerge from the current study, which reports the results of cross-sectional islet autoantibody screening of 220 476 children and follow-up screening of 11 726 children by primary care physicians in Bavaria, Germany, to estimate early-stage type 1 diabetes prevalence and disease progression as detected by public health screening. The findings suggest that the time to seriously consider general population screening has arrived.
The first important conclusion from this study is that the rate of progression from presymptomatic to clinical disease does not differ between children with early-stage type 1 diabetes with a first-degree relative and those without.
Although persons with genetic predisposition are at increased risk for type 1 diabetes development, the vast majority of incident cases have no family history of disease.1,6 Focusing on first-degree relatives has historically been a practical and efficient strategy for identifying at-risk individuals and conducting trials. Much of the natural history data are from cohorts of relatives or individuals identified as having increased high genetic risk.7-9 In December 2024, the American Diabetes Association updated its standards of care to include recommendations for screening “those with a family history of type 1 diabetes or otherwise known elevated genetic risk.”10 Data presented from the Fr1da cohort make it increasingly difficult to justify that narrow focus. In the study by Winkler and colleagues, neither the number or type of autoantibodies identified at initial screening nor the progression to subsequent stages differed among children with multiple autoantibodies with or without a first-degree relative with type 1 diabetes. These findings suggest that without intervention, once islet autoimmunity is established in early-stage type 1 diabetes, a critical threshold has been passed after which progression trajectory appears to be independent of family history. Taken together with the data that 81% of the children diagnosed with early-stage type 1 diabetes progressed to stage 3 disease within the follow-up period, these findings strongly support expanding screening to the general population. At the same time, these data also provide reassurance that the insights, staging frameworks, and trial results historically derived from cohorts of relatives likely remain applicable more broadly.
Second, this study highlights both the feasibility of integrating screening and follow-up into routine clinical care and the essential role of primary care clinicians in this process.
Screening was introduced during well-child visits, with primary care pediatricians serving as the first point of contact for families. These clinicians not only facilitated screening but also delivered initial diagnoses before referring families to specialized diabetes centers. This feasibility is also an important component of Wilson and Jungner’s principles.4 Given shortages in endocrine subspecialists, partnership with primary care colleagues will be critical to sustainable success of screening programs. While participation in the program was voluntary—raising the possibility of selection bias toward more engaged or motivated clinicians—the scale of the study and the duration of follow-up provide compelling evidence that a screening program is both feasible and sustainable in real-world settings. An important next step will be application and refinement of these successful strategies as part of clinical care across different cultures, health care structures, and reimbursement systems. A recent example of note is the national pediatric screening initiative in Italy.11
As observed by the authors, even within established stages, heterogeneity exists in progression rates12 and, as screening efforts expand, more personalized approaches to risk counseling and monitoring will be key to optimize patient care. This could be achieved via risk stratification using individual features such as age and antibody profile or metabolic testing results obtained as part of staging. It should be noted that this study was conducted in a pediatric population, and findings may not be directly generalizable to adults, who have been shown to exhibit variable rates of disease progression.13 However, this limitation does not diminish the importance of the study. Rather, it underscores the need for additional research in adult populations, particularly given that a substantial proportion of new type 1 diabetes diagnoses occur in adulthood.14
Another important consideration is the large population of individuals with a single positive islet autoantibody identified by screening.
This group, which is typically considered as low risk overall, can exhibit substantial heterogeneity in individual risk for type 1 diabetes based on age, genetics, and antibody profile.15 Given this, the single antibody positive population is ideal for precision approaches to monitoring based on personal predictors. Additionally, high-risk individuals with single antibody positivity present a unique opportunity for intervention with disease-modifying therapy early in the disease course, when substantial beta cell mass remains, increasing the potential for beta cell preservation.
Although the authors suggest that these findings may accelerate prevention trials in stage 1 disease by enabling the use of stage progression as a clinical end point, caution is warranted. Simply moving therapies that are effective in later stages to earlier time points may not fully address the underlying biology. The immune response in type 1 diabetes is dynamic and evolves over time,16 and interventions that are effective closer to clinical onset may not have the same impact earlier in the disease course. Thus, these data should serve not only as a catalyst for earlier intervention trials, but also as a call to more precisely define the mechanisms driving disease progression at different stages and to tailor therapies accordingly.
Overall, this study represents a pivotal step forward. The long-standing argument that early-stage disease cannot be readily identified—and therefore cannot efficiently or effectively be studied or targeted—no longer holds.
This study demonstrates that large-scale identification of presymptomatic type 1 diabetes is feasible, at least in pediatric populations. We now find ourselves at a juncture in type 1 diabetes prediction and prevention. The challenge now is no longer whether we can identify individuals at risk, but how to act on that knowledge to alter disease trajectory
LÄS HELA ARTIKELN
https://jamanetwork.com/journals/jama/article-abstract/2849402
Screening Children for Early-Stage Type 1 Diabetes
Key Points
Question
What is the frequency and prognosis of presymptomatic type 1 diabetes in children?
Findings
In a German population-based screening study of islet autoantibody testing in 220 476 children, 590 were diagnosed with early (stage 1 or 2) type 1 diabetes (adjusted population prevalence, 0.3%). Screening identified 81% (212 of 260) of the children who developed clinical (stage 3) type 1 diabetes during follow-up; progression to clinical type 1 diabetes occurred at an annualized rate of 9.6%.
Meaning
These findings inform screening programs to diagnose early-stage type 1 diabetes in children and the design of trials aimed at delaying clinical type 1 diabetes.
Abstract
Importance
Detecting type 1 diabetes in presymptomatic stages is essential for therapies aimed at delaying clinical onset.
Objective
To estimate early-stage (stage 1 or 2) type 1 diabetes prevalence and disease progression to clinical (stage 3) type 1 diabetes in children in a population-based screening study.
Design, Setting, and Participants
From February 2015 to July 2025, children living in Bavaria, Germany, were screened for early-stage type 1 diabetes. Screening was conducted by 716 primary care pediatricians. Screening was performed once in children aged 1.75 to 5.99 years until March 2019 and was subsequently expanded to include up to 2 screenings in children aged 1.75 to 10.99 years. Families of children with early-stage disease were offered diabetes education, metabolic staging, and longitudinal monitoring in 18 specialized diabetes centers.
Exposures
Measurement of islet autoantibodies.
Main Outcomes and Measures The primary outcome was early-stage type 1 diabetes, defined as 2 or more autoantibodies against insulin, glutamic acid decarboxylase, islet antigen-2, or zinc transporter 8 confirmed in consecutive blood samples, with categorization into stages 1 (normoglycemia) and 2 (dysglycemia) and progression to clinical (stage 3) diabetes.
Results
Among 220 476 enrolled children (median [IQR] age, 3.1 [2.2-5.0] years; 106 952 [48.7%] females), 590 had presymptomatic early-stage type 1 diabetes at first screening (adjusted population frequency, 0.3% [95% CI, 0.28%-0.32%]) with prevalences of 0.23% for stage 1 and 0.06% for stage 2 type 1 diabetes. Repeat screening in 11 726 children after a median of 3.3 years identified 29 additional cases. During a median follow-up of 5.7 years, 212 children with an early-stage diagnosis at first screening, 5 with a diagnosis at rescreening, and 43 without an early-stage diagnosis developed clinical (stage 3) diabetes. Five-year progression from early-stage to clinical diabetes was 36.2% (95% CI, 31.2%-40.8%; annualized rate, 9.6%), and not significantly different between children with and without a first-degree family history (P = .54).
Conclusions and Relevance
General population screening of children identified early-stage type 1 diabetes and similar progression rates to clinical diabetes between children with and without a first-degree family history. These findings inform disease-modifying therapy trials and suggest that screening can be considered beyond genetically selected populations.
Trial Registration
ClinicalTrials.gov Identifier: NCT04039945
Nyhetsinfo
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