The American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) recently updated their guidelines for the diagnosis and staging of type 1 diabetes (T1D). These guidelines offer a structured approach to diagnosing and managing T1D from its beginning stages enabling earlier detection and intervention, potentially improving long-term outcomes for at-risk individuals.
T1D is an autoimmune disorder in which islet autoantibodies attack and destroy the beta cells in the pancreas, substantially decreasing insulin production and leading to potentially life-threatening high blood sugar levels. T1D is typically diagnosed in children, though it occasionally manifests in adulthood. About 25 percent of patients with T1D initially present with diabetic ketoacidosis (DKA), which is a life-threatening complication of diabetes where high levels of ketones acidify the blood, leading to long-term repercussions including an increased risk of chronic kidney disease, cardiovascular problems, and potential brain damage.
Currently, testing for T1D is reserved for individuals with affected first degree relatives. However, only 10-15 percent of patients have a family history of T1D, meaning that up to 90 percent of patients are missed using this metric. Broader community-based screening programs would make it much more likely that T1D will be identified in the early stages, which would reduce the risk of severe complications like DKA and provide families with the opportunity to learn about the condition and build a supportive healthcare team.
The approval of the immunotherapy drug teplizumab in 2022 further illustrates the potential benefits of expanding screening. Teplizumab is an anti-CD3 monoclonal antibody that modulates the immune response. It binds to CD3 on T cells, slowing the destruction of insulin-producing beta cells in the pancreas, thereby preserving their function. The resulting delay in symptom onset can give patients additional months or even years before they would need to start insulin therapy. This delay not only improves quality of life but reduces the potential for severe long-term complications. Since teplizumab must be implemented in the early stages of the disease (before symptom onset) to have an effect, community-based screening would help to identify candidates for treatment.
ADA and ISPAD Staging Criteria for Diagnosis of T1D
The new ADA/ISPAD guidelines outline a classification system with three distinct stages that allow for more precise and earlier identification of at-risk individuals through genetic and autoantibody screening.
Stage 1: Autoimmunity without Dysglycemia – At this stage, individuals have at least two islet autoantibodies (the main autoantibodies include islet cell antibodies, glutamic acid decarboxylase antibodies, insulin antibodies, and IA-2 antibodies) but normal blood glucose levels. There are no symptoms of diabetes, but the presence of autoantibodies indicates an increased risk of developing T1D.
Stage 2: Autoimmunity with Dysglycemia – In stage 2, there are at least two islet autoantibodies along with glucose intolerance or dysglycemia that does not meet diagnostic criteria for clinical diabetes. Most individuals at this stage do not experience noticeable symptoms.
Stage 3: Clinical Diabetes – Blood glucose levels are significantly elevated in stage 3, and individuals begin to show mild-to-severe symptoms of diabetes (such as increased thirst, frequent urination, and unexplained weight loss), leading to a formal diagnosis of T1D.
This new metric for staging T1D in children represents a major step forward in the early identification and management of this disease and facilitates the development and expansion of screening programs. Though current guidelines do not recommend screening all children, there is a lot of discussion of the costs and benefits of such a program. Ultimately it will be the insurance companies who decide whether the cost of screening will be offset by the benefit of improved long-term health outcomes and reduced risk of hospitalization for the children who will eventually develop T1D. Regardless, by understanding and implementing these guidelines, healthcare providers can offer earlier and more targeted care, teplizumab can be prescribed in stage 2 to delay onset of stage 3 and delay the need for insulin therapy, and parents can be more proactive in managing their child's health.
As research and technology continue to advance, earlier detection combined with better treatments have strong potential to improve outcomes and quality of life for patients with T1D.
