Materiały źródłowe

• #1 Type 1 Diabetes | Diabetes | CDC

  https://www.cdc.gov/diabetes/about/about-type-1-diabetes.html

  Currently, type 1 diabetes can’t be prevented, but it can be treated effectively. […] No one knows how to prevent type 1 diabetes, but it can be managed successfully by: Following your doctor’s recommendations for living a healthy lifestyle. […] Keeping your blood sugar levels as close to target as possible will help you prevent or delay diabetes-related complications. […] Healthy lifestyle habits are really important too: Making healthy food choices, Being physically active, Managing your blood pressure, Managing your cholesterol. […] Regular appointments with your health care team can help you stay on track with your treatment plan and offer new ideas and strategies if needed.

• #1 Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review | Communications Medicine

  https://www.nature.com/articles/s43856-023-00357-y

  Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. […] We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. […] To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.

• #1 Pathway to Prevention | Type 1 Diabetes TrialNet

  https://www.trialnet.org/our-research/risk-screening

  Pathway to Prevention screening is the first step for all TrialNet prevention studies. Screening is offered at no cost to eligible individuals to evaluate their personal risk of developing the disease. This unique screening can identify the early stages of type 1 diabetes (T1D) years before any symptoms appear. It also helps researchers learn more about how T1D develops and plan new studies exploring ways to prevent it. […] Breakthrough T1D, ADA and Endocrine Society now classify having two or more of these autoantibodies as early stage T1D. […] T1D risk screening will detect if you are in the early stages of T1D. Nearly all people that test positive for two or more diabetes-related autoantibodies will develop the disease. […] Individuals who have two or more autoantibodies are already in early stage T1D. The immune system has started attacking insulin-making beta cells. The lifetime risk of developing clinical diagnosis (stage 3) approaches 100%. […] Come in for a study visit that will include an Oral Glucose Tolerance Test (OGTT). It will show if you have abnormal blood sugar levels and help us determine if you are eligible for a prevention study or further close monitoring for development of T1D.

• #1 Type 1 diabetes mellitus: Prevention and disease-modifying therapy – UpToDate

  https://www.uptodate.com/contents/type-1-diabetes-mellitus-prevention-and-disease-modifying-therapy

  Type 1 diabetes mellitus: Prevention and disease-modifying therapy […] This topic will review strategies to prevent or delay clinical type 1 diabetes during preclinical stages of disease, as well as strategies to preserve insulin secretion after the onset of clinical disease. […] In individuals with preclinical (stage 1 or stage 2) type 1 diabetes, the goal of disease-modifying therapies is to prevent or delay the onset of clinical disease. In individuals with clinical (stage 3) type 1 diabetes, the goal of disease-modifying therapy is to preserve beta cell function and insulin secretion. […] Teplizumab, a humanized anti-CD3 monoclonal antibody, is the only therapy with regulatory approval in the United States for delaying the onset of clinical type 1 diabetes in individuals with preclinical disease.

• #1 Prevention of Type 1 Diabetes – Diabetes in America – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK604182/

  If type 1 diabetes is an immunologically mediated disease, then immune intervention should alter the natural history of the disease and potentially abrogate the clinical syndrome. […] More and more studies have been conducted during the period prior to any evidence of autoimmunity (primary prevention) or after the development of type 1 diabetes-related autoantibodies (secondary prevention). […] This article describes significant progress made toward prevention of type 1 diabetes since the publication of the Diabetes in America, 3rd edition chapter Prevention of Type 1 Diabetes in 2018. […] The goal of such primary and secondary interventions is to arrest the immune process and, thus, prevent or delay clinical disease.

• #1 Prevention of Type 1 Diabetes in Children: A Worthy Challenge?

  https://www.mdpi.com/1660-4601/20/11/5962

  As in many other chronic and non-communicable diseases, prevention consists of three levels of intervention: primary prevention, aimed at avoiding development of autoimmunity against islet autoantigens; secondary prevention, interfering instead with β-cell destruction after the seroconversion; and finally, tertiary prevention, which is focused on preventing the clinical complications of T1D, with the main goal of delaying at least their onset, thus preserving residual β cell-function. […] Primary prevention should start from pregnancy, since the influence of several factors on the risk of developing T1D has been observed in this phase. […] The correlation between maternal weight and the risk of developing T1D has been analyzed in several studies. […] The prevention of excess weight and obesity in women of reproductive age may contribute to a decreased incidence of T1D.

• #1 Prevention of Type 1 Diabetes – Diabetes in America – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK604182/

  Type 1 diabetes results from autoimmune destruction of insulin-producing beta cells. There is a genetic predisposition to the disease, with the greatest contribution conferred by alleles present within the major histocompatibility complex (MHC; known as the human leukocyte antigen [HLA] region) on the short arm of chromosome 6. […] This notion has led to clinical trials to arrest the progression of disease and potentially prevent or reverse the clinical syndrome. […] Clinical trials using various immunologic agents have been conducted at multiple stages of the disease process. Primary prevention trials have been conducted in individuals with genetic predisposition who have not yet developed immunologic markers. […] Future interventions with combinations of agents that can target multiple immunologic mechanisms may be needed, including strategies to improve regulatory immunity, as well as to replace and restore beta cell function.

• #1 Prevention of Type 1 Diabetes: Current Perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10586562/

  Primary prevention strategies for T1D need to be essentially interventions that have a very low potential of inducing harm as the base population is very high and a large majority of them are not going to develop the disease at all. […] These strategies essentially include avoidance of exposure to suspected environmental factors in genetically predisposed populations. […] Therapies involving anti-inflammatory action or immunity-modulating action in general, like the use of docosahexaenoic acid, vitamin D, and high-dose nicotinamide, have been tried with unsuccessful results. […] However, antigenic-specific therapies to induce immune desensitization using the principle of bystander suppression continue to pique the interest of scientists. […] Bystander suppression involves exposure to an antigen similar to a target antigen (against which autoimmunity is to be avoided).

• #1 Prevention of Type 1 Diabetes: Past Experiences and Future Opportunities

  https://www.mdpi.com/2077-0383/9/9/2805

  Prevention of Type 1 Diabetes: Past Experiences and Future Opportunities […] Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing beta-cells in the pancreas, caused by the interplay of genetic and environmental factors. […] Over several decades, multiple clinical trials have attempted to find prevention for T1D in at-risk individuals or to stabilize, ultimately reverse, the disease in those with T1D. […] Despite the introduction of advanced technologies for diabetes management, individuals with T1D may experience a reduced life expectancy; consequently, researchers continue to seek methods not only to prevent T1D, but also to halt progression or even reverse the disease. […] Recently enhanced understanding of the natural history of the disease helped identify earlier pre-symptomatic phases of T1D, from the asymptomatic stage to clinical diagnosis. […] Approaches to prevent T1D include avoidance of environmental triggers of islet autoimmunity, antigen-specific “vaccination” using islet autoantigens, non–antigen-specific systemic therapies, including immunosuppression or immunomodulation, and cellular therapies. […] The target population for primary prevention trials is individuals who carry high-risk genotypes before the first appearance of islet autoantibodies. […] The TRIGR study indicated that a hydrolyzed casein formula did not prevent from developing T1D in genetically at-risk children, and did not delay the onset of the disease. […] Likewise, the Finnish Dietary Intervention Trial for the Prevention of T1D (FINDIA), was designed to determine whether a formula free of bovine insulin may reduce beta-cell autoimmunity. […] This study concluded that late exposure to gluten did not decrease the risk of islet autoimmunity or the development of T1D in genetically at-risk children. […] Vitamin D supplementation in early life has attracted attention as playing a possible role in reducing the risk of T1D in later life. […] More recently, primary intervention trials have started focusing on the modulation of the immune system by antigen-specific immunotherapy (ASI). […] The long-term observations have suggested that certain viral infections may promote the autoimmune attack directed to pancreatic beta-cell in genetically susceptible individuals. […] The link between T1D and CVB infection has prompted efforts to develop vaccines targeting CVBs. […] Secondary prevention is aimed to slow or halt the progressive beta-cell destruction in asymptomatic individuals with persistent islet autoantibodies (stage 1 and 2 of T1D). […] The approach of secondary prevention trials, shown in Table 3, mostly involves the use of nicotinamide, ASI, immunotherapy with monoclonal antibodies, immunosuppressive drugs, hydroxychloroquine, or anti-inflammatory agents. […] Another strategy of secondary prevention is ASI using insulin as the target antigen. […] To date, screening studies have mainly included first-degree relatives of T1D patients. […] The Fr1da Insulin Intervention Study aims to test whether daily administration of up to 67.5 mg oral insulin for 12 months to children with at least two islet autoantibodies will have the potential to control the autoimmune responses by diverting the immune system to a protective rather than destructive response. […] Tertiary prevention is aimed at new-onset patients, at which time the majority of the beta-cell has already been lost. […] Several immunomodulatory and immunosuppressive agents have been investigated, alone or in combination, to halt the destructive autoimmune process of beta-cell that occurs in T1D. […] The main concern about those two agents is that they could have significant side effects, and each had only transient benefit. […] Ultimately, primary prevention of islet autoimmunity will likely be the optimal approach to the prevention of T1D. […]

• #1 Prevention of Type 1 Diabetes in Children: A Worthy Challenge?

  https://www.mdpi.com/1660-4601/20/11/5962

  The study “Diabetes Autoimmunity Study in the Young” (DAISY) evidenced the protective role of maternal intake of vitamin D via food during pregnancy on the risk of the onset of T1D in offspring. […] All RCTs for the primary prevention of T1D have included early life dietary interventions and antigen-based therapy in newborns and toddlers, with the aim being to delay the loss of tolerance against pancreatic autoantigens. […] Vaccines can be one of the strategies on the road to primary prevention of T1D, such as an enteroviral serotypes vaccine. […] A pivotal element in identifying possible new therapeutic strategies is to improve the knowledge of molecular mechanisms underlying the pathogenesis of T1D. […] The aim of prevention is to intervene during the early development of the disease by slowing or halting its progression. […] Screening strategies could allow to identify individuals at risk for T1D in order to enroll them in clinical trials.

• #1 Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol | BMJ Open

  https://bmjopen.bmj.com/content/9/6/e028578

  Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol […] The POInT study, an investigator initiated, randomised, placebo-controlled, double-blind, multicentre primary prevention trial is conducted to determine whether daily administration of oral insulin, from age 4.0 months to 7.0 months until age 36.0 months to children with elevated genetic risk for type 1 diabetes, reduces the incidence of beta-cell autoantibodies and diabetes. […] On the basis of these findings, it is concluded that immune therapy given as a primary prevention strategy must be started early in life. Prevention of beta-cell autoimmunity and T1D would clearly represent a significant advancement.

• #1 Prevention of Type 1 Diabetes – Diabetes in America – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK604182/

  Primary prevention trials have been conducted in birth cohorts identified by genetic screening for high-risk HLA haplotypes (e.g., DR3, DR4), with the interventions initiated at a time when there were neither signs of autoimmunity nor overt metabolic impairment. […] Consequently, most primary prevention trials to date have involved dietary interventions directed at putative environmental triggers, although more recently, oral insulin antigen-specific therapy aimed at inducing early tolerance has been tested. […] Secondary prevention trials are those conducted in individuals with Stage 1 (two or more islet autoantibodies with normoglycemia) or Stage 2 (islet autoantibodies and dysglycemia) type 1 diabetes. […] Initial studies tested nicotinamide (a vitamin B3 derivative) and insulin used in various routes of administration for its potential antigenic effects (to induce immune tolerance).

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Type-1-Diabetes-Prevention.aspx

  Some of the approaches to preventing type 1 diabetes include: […] Immunization – The basic premise of immunization is to alter the active state of the immune system from a Th1 state (the killer cell phase) to the Th2 state when new antibodies are developed. […] Use of DiaPep277 – This is a special protein or peptide fragment of a larger more common protein called the HSP60. This protein helps in bringing about the shift from Th1 to Th2 resulting in acquired immune tolerance. […] Insulin nasal spray – This approach also attempts to achieve a shift from the Th1 to the Th2 state by administering insulin to the immune cells within the nose. […] Use of BCG vaccine – The Bacillus Calmette-Gurin (BCG) vaccine is a vaccine used against tuberculosis. It helps produce tumor necrosis factor-alpha, or TNF-, which is deficient in people with type 1 diabetes. […] Use of the Diamyd vaccine – This involves injections of an autoantigen called GAD65. This delays the onset of disease in individuals who are susceptible to type 1 diabetes by producing the anti-inflammatory regulatory cytokines that protect the beta cells.

• #1 New Ways to Prevent Type 1 Diabetes Under Investigation at Columbia | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/new-ways-prevent-type-1-diabetes-under-investigation-columbia

  Relatives of people with type 1 diabetes are 15 times more likely than the general population to develop the autoimmune disease. […] At Columbias Naomi Berrie Diabetes Center, relatives of people with type 1 diabetes who have not yet developed symptoms can enroll in studies being conducted to uncover why the disease develops and how its development could be delayed or prevented. […] People who are at risk may be eligible for other TrialNet studies that will help researchers learn more about how type 1 diabetes develops and explore ways to prevent it. […] TrialNets hydroxychloroquine prevention study is the first study to investigate if the drug can prevent or delay type 1 diabetes in people with multiple diabetes antibodies. […] A new experimental treatment aims to prevent type 1 diabetes by retraining the immune system to stop its attack on the patients insulin-producing cells.

• #1 Teplizumab is the first drug to delay the diagnosis of T1D for a median of two years | Type 1 Diabetes TrialNet

  https://www.trialnet.org/events-news/blog/teplizumab-first-drug-delay-diagnosis-t1d-median-two-years

  Teplizumab is the first drug to delay the diagnosis of T1D for a median of two years. […] This is the first study to show any drug can delay type 1 diabetes diagnosis a median of 2 years in people at high risk, explains Dr. Herold. […] This study highlights that type 1 diabetes is an autoimmune disease that can be delayed with immunotherapy. […] TrialNet is continually planning and launching new studies. And, we always encourage family members of people with T1D to get screened through the Pathway to Prevention study.

• #1 Type 1 diabetes mellitus: Prevention and disease-modifying therapy – UpToDate

  https://www.uptodate.com/contents/type-1-diabetes-mellitus-prevention-and-disease-modifying-therapy

  In the United States, teplizumab is approved for individuals aged 8 years and older who have stage 2 type 1 diabetes (≥2 diabetes-related autoantibodies and dysglycemia) and is administered as a single 14-day course of daily intravenous infusions. […] The availability of teplizumab represents a paradigm shift in the treatment of type 1 diabetes; with enhanced understanding of disease pathogenesis and progression, type 1 diabetes can be identified and treated in its preclinical stages before the development of symptomatic hyperglycemia. […] In individuals with clinical (stage 3) type 1 diabetes, the goal of disease-modifying therapy is to preserve beta cell function and insulin secretion. […] Preservation of endogenous insulin secretion after the clinical diagnosis of type 1 diabetes is associated with enduring benefits, including reduced risks of microvascular complications and severe hypoglycemia.

• #1 Type 1 diabetes – Wikipedia

  https://en.wikipedia.org/wiki/Type_1_diabetes

  There have also been clinical trials attempting to induce immune tolerance by vaccination with insulin, GAD65, and various short peptides targeted by immune cells during type 1 diabetes; none have yet delayed or prevented development of disease. […] Several trials have attempted dietary interventions with the hope of reducing the autoimmunity that leads to type 1 diabetes. Trials that withheld cow’s milk or gave infants formula free of bovine insulin decreased the development of -cell-targeted antibodies, but did not prevent the development of type 1 diabetes. Similarly, trials that gave high-risk individuals injected insulin, oral insulin, or nicotinamide did not prevent diabetes development. […] Other strategies under investigation for the prevention of type 1 diabetes include gene therapy, stem cell therapy, and modulation of the gut microbiome. Gene therapy approaches, while still in early stages, aim to alter genetic factors that contribute to beta-cell destruction by editing immune responses.

• #1 Type 1 diabetes – Wikipedia

  https://en.wikipedia.org/wiki/Type_1_diabetes

  Tolerogenic therapies, which seek to induce immune tolerance to beta-cell antigens, are another area of interest. Techniques such as using dendritic cells or regulatory T cells engineered to promote tolerance to beta cells are being studied in clinical trials, though these approaches remain experimental. […] There is also a hypothesis that certain viral infections, particularly enteroviruses, may trigger type 1 diabetes in genetically predisposed individuals. Researchers are investigating whether vaccines targeting these viruses could reduce the risk of developing the disease. […] Combination immunotherapies are being explored as well, with the aim of achieving more durable immune protection by using multiple agents together. For example, anti-CD3 antibodies may be combined with other immunomodulatory agents such as IL-1 blockers or checkpoint inhibitors. […] Finally, researchers are studying how environmental factors such as infections, diet, and stress may affect immune regulation through epigenetic modifications. The hope is that targeting these epigenetic changes could delay or prevent the onset of type 1 diabetes in high-risk individuals.

• #1 Type 1 Diabetes: Causes, Symptoms, Complications & Treatment

  https://my.clevelandclinic.org/health/diseases/21500-type-1-diabetes

  Is Type 1 diabetes preventable? Unfortunately, theres nothing you can do to prevent developing Type 1 diabetes. […] Since Type 1 diabetes can run in families, your healthcare provider can test your family members for the autoantibodies that cause the disease. Type 1 Diabetes TrialNet, an international research network, also offers autoantibody testing to family members of people with Type 1 diabetes. […] The presence of autoantibodies, even without diabetes symptoms, means youre more likely to develop Type 1 diabetes. If you have a sibling, child or parent with Type 1 diabetes, you may want to get an autoantibody test. These tests can help catch Type 1 diabetes in its earliest phases.

• #1 T1D Screening and Prevention Program | Texas Children’s

  https://www.texaschildrens.org/departments/t1d-screening-and-prevention-program

  Screening and Intervention to Delay Type 1 Diabetes (T1D) is available via our telemedicine-based program called SIT Down T1D! The program is for children and adolescents under the age of 18 who are at risk for developing type 1 diabetes. These individuals usually have a family member with T1D, who, in most cases, will be a sibling. […] This program at Texas Children’s Diabetes and Endocrinology Care Center is one of the first comprehensive clinical programs for screening, staging and delaying type 1 diabetes nationwide. Our goals are to delay type 1 diabetes, prevent diabetic ketoacidosis (DKA) and serve as a valuable resource to patients and families. […] We can identify people with early stages of T1D, even before symptoms and the need for insulin arise. One useful way is screening for autoantibodies, which indicate the autoimmune process in the pancreas has begun.

• #1 Session to examine the emerging potential of immunotherapy in type 1 diabetes prevention – ADA Meeting News

  https://www.adameetingnews.org/session-to-examine-the-emerging-potential-of-immunotherapy-in-type-1-diabetes-prevention/

  Session to examine the emerging potential of immunotherapy in type 1 diabetes prevention […] In November 2022, the U.S. Food and Drug Administration approved teplizumab, a CD3-directed monoclonal antibody and the first drug to be approved for the delay and prevention of type 1 diabetes. […] This trial demonstrated that teplizumab treatment delayed progress to stage 3, or clinically diagnosed, type 1 diabetes by a median of two years. […] While teplizumab represents an exciting start to achieving the delay and prevention of type 1 diabetes in those at high risk for progression to clinical type 1 diabetes, Dr. Leschek said that a single course of teplizumab alone may delay type 1 diabetes but is not likely to be sufficient for prevention. […] There is a need to study additional agents, some of which may prove to be more effective, safe, and durable than teplizumab. […] Additionally, there is a need to study teplizumab, and potentially other drugs, in combination with other agents to achieve a more durable effect and minimize toxicity.

• #1 Promising Drug Candidate Identified for Type 1 Diabetes Prevention | Technology Networks

  https://www.technologynetworks.com/drug-discovery/news/promising-drug-candidate-identified-for-type-1-diabetes-prevention-367478

  According to a study, type 1 diabetes could be prevented by inhibiting a gene associated with the onset of the disease. […] Under the direction of Professor Timo Otonkoski, researchers at the University of Helsinki have investigated the mechanisms of action of the risk genes associated with type 1 diabetes with the aim of finding novel methods for the prevention of the disease. […] The assumption was confirmed in the study, and the destruction of beta cells was effectively stopped by inhibiting TYK2 expression. […] In light of the findings, a TYK2 inhibitor is a promising drug candidate for the prevention of type 1 diabetes. […] According to Otonkoski, the effect of TYK2 inhibitors in the prevention of diabetes must next be carefully investigated in animal models. If the results are positive, the next step to clinical trials can be taken.

• #1 Breakthrough Drug Helps Children with New-Onset Type 1 Diabetes | UC San Francisco

  https://www.ucsf.edu/news/2023/10/426396/breakthrough-drug-helps-children-new-onset-type-1-diabetes

  The current study is the culmination of a series of earlier, smaller studies in new onset type 1 diabetes that suggested teplizumab would be safe and effective in preserving beta cell function. […] Their pivotal 2019 trial led to the FDA approval in late 2022 of teplizumab by showing that a 14-day dose of the drug delayed by an average of three years the onset of type 1 diabetes in children and adults who were at risk of developing the condition. […] Gitelman is already thinking about next steps. His team continues to follow the PROTECT patients to see how long the effects of the current therapy may last, and sees potential for studying whether these patients, or future ones, might benefit from additional teplizumab infusions at later time points. […] A study is now being launched to evaluate the benefits of teplizumab when given to children under age 8 at risk for type 1 diabetes.

• #1 Turning a corner in the prevention of Type 1 diabetes

  https://www.openaccessgovernment.org/prevention-of-type-1-diabetes/73880/

  This year marked a significant milestone for Type 1 diabetes. After more than three decades of clinical trials, each one providing important learnings for the next, the research community reached the positive outcome they had been waiting for: it was possible to delay the diagnosis of Type 1 diabetes. […] This finding has sparked a wave of new possibilities, but importantly it provides much-needed confirmation that tackling the root cause of Type 1 the immune attack against insulin-producing beta cells in the pancreas has been the right strategy. […] Witnessing Teplizumab, an anti-CD3 antibody, delay the onset of Type 1 diabetes by an average of two years, is the result of a mammoth effort to piece together the underlying pathology of this condition. […] Two years free of insulin therapy, sleepless nights, or the worry of future complications.

• #1 UCSF Diabetes Type 1 Clinical Trials for 2025 — San Francisco Bay Area

  https://clinicaltrials.ucsf.edu/diabetes-type-1

  TrialNet Pathway to Prevention of T1D: Rationale: The accrual of data from the laboratory and from epidemiologic and prevention trials has improved the understanding of the etiology and pathogenesis of type 1 diabetes mellitus (T1DM). […] TrialNet is dedicated to testing new approaches to the prevention of and early intervention for type 1 diabetes. […] The goal of the TrialNet Natural History Study of the Development of Type 1 Diabetes is to enhance our understanding of the demographic, immunologic, and metabolic characteristics of individuals at risk for developing type 1 diabetes. […] TrialNet will identify adults and children at risk for developing diabetes by testing for the presence of these antibodies in the blood. […] If this test is positive, additional testing will be offered to determine the likelihood that a person may develop diabetes.

• #1 Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol | BMJ Open

  https://bmjopen.bmj.com/content/9/6/e028578

  The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) was initiated in 2015. It is a consortium of several European research institutions providing an international infrastructure that enables type 1 diabetes primary prevention trials. GPPAD conducts testing for the identification of newborns and infants who have an increased risk for type 1 diabetes, and clinical trials that test primary prevention strategies. […] It is widely held that if infant tolerance to beta-cell autoantigens could be enhanced, this could prevent or delay the onset of presymptomatic or asymptomatic T1D (defined as multiple beta-cell autoantibodies), and hence prevent or delay disease diagnosis. […] Our goal is to introduce immune tolerance to autoantigen before the start of beta-cell autoimmunity as primary prevention for T1D.

• #1 Prevention of Type 1 Diabetes in Children: A Worthy Challenge?

  https://www.mdpi.com/1660-4601/20/11/5962

  Prevention of Type 1 Diabetes in Children: A Worthy Challenge? […] The ability to intercept individuals at high risk of developing type 1 diabetes is the first step toward the development of therapies that can delay the process of β-cell destruction, thus permitting a better glycemic control and reducing the incidence of ketoacidosis. […] The adoption of Eisenbarth and Insel’s pathogenetic staging of T1D has provided not only a standardized taxonomy, but also the possibility to identify subjects at risk of developing T1D, thus paving the way to its prevention. […] About 15,000 children and young adults who are first- or second-degree relatives of individuals with T1D are screened annually for islet autoantibodies through TrialNet. […] The long-term goal of the TEDDY study was the identification of infectious agents, dietary factors, or other environmental agents, including psychosocial factors, that could trigger or protect from T1D in genetically susceptible individuals.

• #1 Type 1 Diabetes Prediction and Prevention (DIPP) Study | Clinical Research Trial Listing

  https://www.centerwatch.com/clinical-trials/listings/NCT03269084/type-1-diabetes-prediction-and-prevention-dipp-study

  The Type 1 Diabetes Prediction and Prevention (DIPP) Study in Finland is a population-based long-term clinical follow-up study established since 1994 in three university hospitals in Finland to understand the pathogenesis of type 1 diabetes (T1D), predict the disease, and find preventive treatment. […] It has been estimated that 5% of children in the follow-up will develop T1D and 60% of future T1D cases will be reached by the current screening and follow-up strategy.

• #1 Type 1 Diabetes Prevention Program at CHOP | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/type-1-diabetes-prevention-program-chop

  Tzield, the first FDA-approved treatment to delay the onset of clinical diabetes, is now available for children who need it. […] This treatment, also called teplizumab, addresses the underlying autoimmune process of type 1 diabetes (T1D) and can delay the onset of clinical diabetes by up to two years. […] Since early identification is crucial to ensure timely initiation of treatment, Childrens Hospital of Philadelphia (CHOP) has developed a specialized clinic designed for at-risk children. Our mission is to provide monitoring and treatment options for those who are eligible. The program also tracks those who may be at risk but do not yet qualify for treatment and closely monitors individuals receiving treatment. […] We offer screening services and provide access to clinical research trials aimed at preventing T1D for individuals diagnosed in the early stages. Screening for T1D allows for early detection and can help prevent diabetic ketoacidosis, potentially reducing prolonged hospitalizations and the emotional strain of caring for a sick child.

• #1

  https://journals.lww.com/indjem/fulltext/2023/07000/prevention_of_type_1_diabetes__current_perspective.2.aspx

  These strategies essentially include avoidance of exposure to suspected environmental factors in genetically predisposed populations. […] Therapies involving anti-inflammatory action or immunity-modulating action in general, like the use of docosahexaenoic acid, vitamin D, and high-dose nicotinamide, have been tried with unsuccessful results. […] However, antigenic-specific therapies to induce immune desensitization using the principle of bystander suppression continue to pique the interest of scientists. […] Teplizumab has provided the right kind of morale booster to the field of T1D prevention which had seen dismal results so far. […] Teplizumab delays the onset of T1DM by months-years and does not fully prevent it. […] Recent success in preventive therapies for type 1 diabetes has rekindled the hope of diabetes-free life in susceptible individuals. […] Teplizumab has initiated the cascade (hopefully) of successful immunotherapies for secondary and tertiary prevention; identifying eligible people is still a problem to be solved though. […] However, there is still a long way to go in designing ideal prevention therapies for T1D.

• #1 Prevention of Type 1 Diabetes: Current Perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10586562/

  People living with type 1 Diabetes (T1D) and their families have poor perception of health related quality of life. […] Prevention of T1D, if successful, has potential to change lives of millions of families across the globe. […] Identifying underlying primary antigen responsible for initiating autoimmune cascade, avoiding environmental trigger and modifying immunity has all been used as strategies for preventing or delaying onset of type 1 diabetes. […] Primary prevention for type 1 diabetes is hindered by difficulty in identifying at-risk population and also due to lack of effective preventive strategy. […] Secondary prevention, in children with presence of autoimmunity, has recently received a boost with approval of Teplizumab, an immunity modifying drug by its Anti-CD3 action. […] Application of preventive strategies would also change based on country specific incidence, prevalence and availability of health resources.

• #1 Type 1 Diabetes Prevention: a systematic review of studies testing disease-modifying therapies and features linked to treatment response | medRxiv

  https://www.medrxiv.org/content/10.1101/2023.04.12.23288421v1

  Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Efforts to prevent T1D have focused on modulating immune responses and supporting beta cell health; however, heterogeneity in disease progression and responses to therapies have made these efforts difficult to translate to clinical practice, highlighting the need for precision medicine approaches to T1D prevention. […] We identified 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss in individuals at disease onset. […] While the quality of prevention and intervention trials was overall high, low quality of precision analyses made it difficult to draw meaningful conclusions that inform clinical practice. Thus, prespecified precision analyses should be incorporated into the design of future studies and reported in full to facilitate precision medicine approaches to T1D prevention. […] T1D prevention remains an elusive goal, largely due to immense variability in disease progression. Agents tested to date in clinical trials work in a subset of individuals, highlighting the need for precision medicine approaches to prevention.

• #1 Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review | Communications Medicine

  https://www.nature.com/articles/s43856-023-00357-y

  While the overall quality of trials was high, studies testing individual features affecting responses to treatments were low. […] This review reveals an important need to carefully plan high-quality analyses of features that affect treatment response in T1D, to ensure that tailored approaches may one day be applied to clinical practice. […] Given that agents targeting these pathways may have potential adverse effects, and initial therapies may affect the efficacy and safety of subsequent treatment approaches, precision medicine is uniquely poised to identify which individuals stand to benefit the most from a given intervention and to optimize potential risk-benefit ratios for treated persons. […] T1D development occurs along a spectrum of progressive beta cell destruction, beginning with loss of tolerance, reflected by the appearance of islet autoantibodies, and continuing with progressive hyperglycemia, abnormal glucose tolerance, and decline in endogenous insulin production, reflected by a decline in C-peptide.

• #1 Preventing Type 1 diabetes

  https://www.myhealthexplained.com/diabetes-information/diabetes-articles/type-1-diabetes-prevention

  There are a number of different agents that have been studied to decrease the immune-mediated destruction of beta cells in the pancreas. These include immunosuppressive and immunomodulatory agents and other drugs that may be given alone or in combination to decrease beta cell destruction (Prediction and Prevention of Type 1 Diabetes: Progress, Problems, and Prospects). Most of the studies that have been conducted, have focused on preserving any remaining beta-cell function in people who have been recently diagnosed with type 1 diabetes. […] In June 2019, TrialNet presented findings from their most recent study (Teplizumab for treatment of type 1 diabetes (Protg study): 1-year results from a randomised, placebo-controlled trial) at the 2019 American Diabetes Associations 79th Scientific Sessions. The study was the first of its kind to demonstrate the potential for preventing type 1 diabetes in those who are at a high risk of developing the condition. The study showed that the immunotherapy drug teplizumab delayed the diagnosis of type 1 diabetes, on average, by 2 years in children and adults at high risk. […] Its still early days and more research and trials need to be done into the prevention of type 1 diabetes.

• #1 Type 1 Diabetes | International Diabetes Federation

  https://idf.org/about-diabetes/types-of-diabetes/type-1-diabetes/

  Type 1 diabetes cannot currently be prevented and there is no cure for the condition. […] Regular physical activity dramatically benefits people with type 1 diabetes. […] People with type 1 diabetes can eat a variety of food without restrictions. […] However, to help keep blood glucose levels within the target range and delay or avoid diabetes-related complications, people with type 1 diabetes should eat healthy, balanced meals that include all major food groups.

• #1 100 YEARS OF INSULIN: Arresting or curing type 1 diabetes: an elusive goal, but closing the gap in: Journal of Endocrinology Volume 249 Issue 2 (2021)

  https://joe.bioscientifica.com/view/journals/joe/249/2/JOE-20-0552.xml

  To date, the standard biomarkers are genetic markers and autoantibodies. […] This highlights the need for true biomarkers in T1D and makes it the major focus of research in INNODIA. […] The final goal in T1D is the re-establishment of antigen-specific tolerance. […] The major lesson learned from these trials is that the antigen-specific interventions tested were safe. […] As to date, none has shown prevention or long-term disease reversal, indicating that lasting prevention and/or cure will depend on combination therapies.

• #2 Type 1 Diabetes: Causes, Symptoms, Complications & Treatment

  https://my.clevelandclinic.org/health/diseases/21500-type-1-diabetes

  Is Type 1 diabetes preventable? Unfortunately, theres nothing you can do to prevent developing Type 1 diabetes. […] Since Type 1 diabetes can run in families, your healthcare provider can test your family members for the autoantibodies that cause the disease. Type 1 Diabetes TrialNet, an international research network, also offers autoantibody testing to family members of people with Type 1 diabetes. […] The presence of autoantibodies, even without diabetes symptoms, means youre more likely to develop Type 1 diabetes. If you have a sibling, child or parent with Type 1 diabetes, you may want to get an autoantibody test. These tests can help catch Type 1 diabetes in its earliest phases.

• #2 Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review | Communications Medicine

  https://www.nature.com/articles/s43856-023-00357-y

  While the overall quality of trials was high, studies testing individual features affecting responses to treatments were low. […] This review reveals an important need to carefully plan high-quality analyses of features that affect treatment response in T1D, to ensure that tailored approaches may one day be applied to clinical practice. […] Given that agents targeting these pathways may have potential adverse effects, and initial therapies may affect the efficacy and safety of subsequent treatment approaches, precision medicine is uniquely poised to identify which individuals stand to benefit the most from a given intervention and to optimize potential risk-benefit ratios for treated persons. […] T1D development occurs along a spectrum of progressive beta cell destruction, beginning with loss of tolerance, reflected by the appearance of islet autoantibodies, and continuing with progressive hyperglycemia, abnormal glucose tolerance, and decline in endogenous insulin production, reflected by a decline in C-peptide.

• #2 100 YEARS OF INSULIN: Arresting or curing type 1 diabetes: an elusive goal, but closing the gap in: Journal of Endocrinology Volume 249 Issue 2 (2021)

  https://joe.bioscientifica.com/view/journals/joe/249/2/JOE-20-0552.xml

  Type 1 diabetes is one of the most common chronic diseases in children and adolescents, but remains unpreventable and incurable. […] The disease-associated complications remain the true burden of affected individuals and necessitate the search for disease prevention and reversal. […] Moreover, robust and reliable biomarkers to detect type 1 diabetes in the early (pre-symptomatic) phases are wanted to preserve functional beta cell mass. […] The best predictor of progression toward T1D in genetically predisposed individuals, but also in the general population, is the presence of autoantibodies. […] Therefore, when using islet autoantibodies in the prediction of T1D onset, it is important to understand their implication. […] Thus, although autoantibodies are at present the best biomarker, finding better biomarkers is a priority on the path to T1D prevention or cure.

• #2 Prevention of Type 1 Diabetes: Current Perspective

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10586562/

  People living with type 1 Diabetes (T1D) and their families have poor perception of health related quality of life. […] Prevention of T1D, if successful, has potential to change lives of millions of families across the globe. […] Identifying underlying primary antigen responsible for initiating autoimmune cascade, avoiding environmental trigger and modifying immunity has all been used as strategies for preventing or delaying onset of type 1 diabetes. […] Primary prevention for type 1 diabetes is hindered by difficulty in identifying at-risk population and also due to lack of effective preventive strategy. […] Secondary prevention, in children with presence of autoimmunity, has recently received a boost with approval of Teplizumab, an immunity modifying drug by its Anti-CD3 action. […] Application of preventive strategies would also change based on country specific incidence, prevalence and availability of health resources.

• #2 Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol | BMJ Open

  https://bmjopen.bmj.com/content/9/6/e028578

  The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) was initiated in 2015. It is a consortium of several European research institutions providing an international infrastructure that enables type 1 diabetes primary prevention trials. GPPAD conducts testing for the identification of newborns and infants who have an increased risk for type 1 diabetes, and clinical trials that test primary prevention strategies. […] It is widely held that if infant tolerance to beta-cell autoantigens could be enhanced, this could prevent or delay the onset of presymptomatic or asymptomatic T1D (defined as multiple beta-cell autoantibodies), and hence prevent or delay disease diagnosis. […] Our goal is to introduce immune tolerance to autoantigen before the start of beta-cell autoimmunity as primary prevention for T1D.

• #2 Type 1 diabetes – Wikipedia

  https://en.wikipedia.org/wiki/Type_1_diabetes

  Tolerogenic therapies, which seek to induce immune tolerance to beta-cell antigens, are another area of interest. Techniques such as using dendritic cells or regulatory T cells engineered to promote tolerance to beta cells are being studied in clinical trials, though these approaches remain experimental. […] There is also a hypothesis that certain viral infections, particularly enteroviruses, may trigger type 1 diabetes in genetically predisposed individuals. Researchers are investigating whether vaccines targeting these viruses could reduce the risk of developing the disease. […] Combination immunotherapies are being explored as well, with the aim of achieving more durable immune protection by using multiple agents together. For example, anti-CD3 antibodies may be combined with other immunomodulatory agents such as IL-1 blockers or checkpoint inhibitors. […] Finally, researchers are studying how environmental factors such as infections, diet, and stress may affect immune regulation through epigenetic modifications. The hope is that targeting these epigenetic changes could delay or prevent the onset of type 1 diabetes in high-risk individuals.

• #2 Type 1 diabetes mellitus: Prevention and disease-modifying therapy – UpToDate

  https://www.uptodate.com/contents/type-1-diabetes-mellitus-prevention-and-disease-modifying-therapy

  Type 1 diabetes mellitus: Prevention and disease-modifying therapy […] This topic will review strategies to prevent or delay clinical type 1 diabetes during preclinical stages of disease, as well as strategies to preserve insulin secretion after the onset of clinical disease. […] In individuals with preclinical (stage 1 or stage 2) type 1 diabetes, the goal of disease-modifying therapies is to prevent or delay the onset of clinical disease. In individuals with clinical (stage 3) type 1 diabetes, the goal of disease-modifying therapy is to preserve beta cell function and insulin secretion. […] Teplizumab, a humanized anti-CD3 monoclonal antibody, is the only therapy with regulatory approval in the United States for delaying the onset of clinical type 1 diabetes in individuals with preclinical disease.

• #2 Type 1 Diabetes Prevention Program at CHOP | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/type-1-diabetes-prevention-program-chop

  Tzield, the first FDA-approved treatment to delay the onset of clinical diabetes, is now available for children who need it. […] This treatment, also called teplizumab, addresses the underlying autoimmune process of type 1 diabetes (T1D) and can delay the onset of clinical diabetes by up to two years. […] Since early identification is crucial to ensure timely initiation of treatment, Childrens Hospital of Philadelphia (CHOP) has developed a specialized clinic designed for at-risk children. Our mission is to provide monitoring and treatment options for those who are eligible. The program also tracks those who may be at risk but do not yet qualify for treatment and closely monitors individuals receiving treatment. […] We offer screening services and provide access to clinical research trials aimed at preventing T1D for individuals diagnosed in the early stages. Screening for T1D allows for early detection and can help prevent diabetic ketoacidosis, potentially reducing prolonged hospitalizations and the emotional strain of caring for a sick child.

• #2 Type 1 Diabetes Prevention Program at CHOP | Children’s Hospital of Philadelphia

  https://www.chop.edu/news/type-1-diabetes-prevention-program-chop

  We offer access to Tzield (teplizumab) at our clinic for eligible candidates. This innovative treatment marks a significant advancement in managing early T1D. Our team will work closely with patients and their families to assess whether teplizumab is the right option, ensuring personalized and effective care at every stage of the process.

• #2 Type 1 diabetes mellitus: Prevention and disease-modifying therapy – UpToDate

  https://www.uptodate.com/contents/type-1-diabetes-mellitus-prevention-and-disease-modifying-therapy/print

  Many therapeutic strategies have been investigated for preserving beta cell function after the clinical diagnosis of type 1 diabetes. Although no immune-modulating therapies are approved for use in clinical (stage 3) type 1 diabetes, several have demonstrated a reasonable risk profile and the capacity to modify the underlying disease and preserve insulin secretion.

• #2 Type 1 Diabetes TrialNet » Diabetes Institute » College of Medicine » University of Florida

  https://diabetes.ufl.edu/research/programs/trialnet/

  Type 1 Diabetes TrialNet is an NIH-sponsored clinical trials network of researchers dedicated to the study, prevention, and early treatment of type 1 diabetes. […] The purpose of TrialNet is to: […] Conduct studies designed to evaluate new approaches to prevent or ameliorate type 1 diabetes; and […] University of Florida TrialNet researchers seek to identify family members at risk, and evaluate promising new therapies to prevent, slow or reverse the progression of the disease. […] The Pathway to Prevention study offers a blood test that can identify the risk for type 1 diabetes up to 10 years before symptoms actually appear.

• #2 T1D Screening and Prevention Program | Texas Children’s

  https://www.texaschildrens.org/departments/t1d-screening-and-prevention-program

  By identifying T1D early, it may be possible to prevent the onset of diabetic ketoacidosis (DKA), one of the most serious outcomes of diabetes that includes high blood glucose and ketone levels. […] We provide laboratory screening for autoantibodies, staging of T1D, monitoring for progression, and counseling on Tzield (teplizumab) if eligible. […] Tzield (teplizumab) is an FDA-approved medication now available for patients 8 years and older that has been shown to delay the onset of insulin-required T1D by approximately 2 years, on average.

• #2 Turning a corner in the prevention of Type 1 diabetes

  https://www.openaccessgovernment.org/prevention-of-type-1-diabetes/73880/

  But perhaps the two-year delay offered by Teplizumab could be extended and if subsequent trial results lead to a license for those at high risk future real-world data could paint a clearer picture of Teplizumab’s long-term prevention effects. […] Each step forward in our understanding of how to prevent or delay the onset of Type 1 diabetes brings us closer to finding a cure. A possible future scenario is one where we can combine a treatment to stop the immune attack with another to replace or regenerate lost beta cells. So research must continue.

• #2 New Drug Shown to Delay Onset of Type 1 Diabetes – Cincinnati Children’s Blog

  https://blog.cincinnatichildrens.org/research-and-discoveries/new-drug-delays-onset-type-1-diabetes/

  The Cincinnati Children’s Division of Endocrinology is ready to administer teplizumab to any patients who qualify. […] To address the increasing cases of early-stage diabetes that are identified through screenings in pediatric patients, we’ve created a Diabetes Prevention Clinic to follow patients with stage 1 and stage 2 type 1 diabetes.

• #2 Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review | Communications Medicine

  https://www.nature.com/articles/s43856-023-00357-y

  While an ideal goal is clinical T1D prevention, disease-modifying agents aimed throughout the spectrum of T1D progression have the potential to improve long-term outcomes. […] Our review identified noteworthy progress towards defining effective disease-modifying therapies for T1D but a need for better quality data to support the existence of individual features consistently linked to differences in treatment response.

• #2 Teplizumab in Type 1 Diabetes Mellitus: An Updated Review – touchENDOCRINOLOGY

  https://touchendocrinology.com/diabetes/journal-articles/teplizumab-in-type-1-diabetes-mellitus-an-updated-review/

  Teplizumab became the first immunomodulatory agent to be licensed by the US Food and Drug Administration for delaying the onset of T1DM in high-risk adults and children over 8 years old. […] Teplizumab use could lead to a transient systemic rise in the percentage of CD4+Foxp3+ T cells, thereby restoring the imbalance between tolerogenic Tregs and pathogenic T-cells. […] Teplizumab delays the onset of T1DM in high-risk relatives of individuals with T1DM. […] Following a single course of a 14-day infusion of teplizumab, the median time to T1DM diagnosis was 48.4 months in the teplizumab group and 24.4 months in the placebo group. […] Teplizumab improves insulin production, which was measured using the C-peptide response, and -cell function. […] Therefore, it was concluded that teplizumab delays the progression to clinical T1DM in high-risk individuals.

• #3 Type 1 Diabetes Drug, Teplizumab, Has Additional Benefits, New Study Shows > News > Yale Medicine

  https://www.yalemedicine.org/news/teplizumab-new-diabetes-drug

  In 2022, the Food and Drug Administration (FDA) approved a medication that can delay the onset of type 1 diabetes marking the first treatment to change the course of this autoimmune disease since the discovery of insulin in 1922. […] The goal of teplizumab is to delay the onset of clinical diabetes, with the classic symptoms of excessive urination and thirst and other complications, as long as possible. Researchers say the drug postpones the median onset of the disease by at least two years. […] Dr. Herold says the promising news with teplizumab is that it is the starting point to prevent the disease from occurring or even to restore lost beta cells. Combining treatments may prolong and enhance responses in those at risk for type 1 diabetes.

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