Screening
Screening tests are generally most applicable to prediabetes and type 2 diabetes; however, several screening programs for type 1 diabetes are available in the US (e.g., trialnet.org, askhealth.org, and cascadekids.org), Europe (e.g., Fr1da and gppad.org), and Australia (e.g., type1screen.org) through enrolment in research studies.[1] Early detection of preclinical type 1 diabetes through screening for autoantibodies and monitoring metabolic changes offers several key benefits. These include identifying individuals who may be eligible for disease-modifying therapies, providing early access to diabetes education and support services, and potentially mitigating the severity of the disease at the time of diagnosis, with evidence showing that such monitoring in research studies can significantly reduce the incidence of diabetic ketoacidosis (DKA) at diagnosis (although the impact of monitoring in general clinical practice on DKA rates is not known).[82] Decades of research and monitoring of individuals with islet autoantibody positivity has led to the paradigm shift that type 1 diabetes is a continuum of stages, from genetic risk through to autoimmunity and then metabolic disease.[82]
The American Diabetes Association (ADA) has produced a staging system for type 1 diabetes based on clinical features, glycemic levels, and presence of autoantibodies:[1]
Stage 1: presence of autoimmunity (i.e., multiple islet autoantibodies) in the absence of dysglycemia (i.e., presymptomatic). Five-year risk of developing symptomatic type 1 diabetes is approximately 44% overall, but varies considerably based on number, titer, and specificity of autoantibodies, as well as age of seroconversion and genetic risk.
Stage 2: autoimmunity and dysglycemia in the prediabetic range (i.e., presymptomatic). Risk of developing a clinical diagnosis of type 1 diabetes is approximately 60% by 2 years and 75% by 5 years.
Stage 3: autoimmunity with overt hyperglycemia (symptomatic; i.e., clinical type 1 diabetes).
The International Society for Pediatric and Adolescent Diabetes (ISPAD) has published a similar staging system.[48] It specifies that the presence of multiple islet autoantibodies should be confirmed on at least 2 samples and further classifies stage 2 into 2a, for those with marginally raised glucose levels, and 2b, for those with glucose levels nearing stage 3. Stage 3 is subclassified into 3a, which describes those who are asymptomatic but who meet glycemic diagnostic criteria, and 3b, which includes those patients who present with classic onset of disease, with overt hyperglycemia, acute symptoms (e.g., polyuria, polydipsia, and unexplained weight loss), and an immediate need for insulin initiation.[48] ISPAD guidelines also include stage 4, which describes patients with "long-standing" or "established" diabetes.[48]
Screening for presymptomatic type 1 diabetes may be done by detection of autoantibodies to insulin, glutamic acid decarboxylase (GAD), islet tyrosine phosphatase 2 (IA-2), or zinc transporter 8 (ZnT8).[1] The presence of multiple confirmed islet autoantibodies is a risk factor for clinical diabetes.[1] Testing for dysglycemia may be used to further forecast near-term risk.[1] The ADA and European Association for the Study of Diabetes have published consensus guidelines for monitoring of people with islet autoantibody positivity, caveating that current insights are largely derived from research studies of individuals known to be at risk for type 1 diabetes and that general population data are less extensive.[82]
Currently, screening of individuals for islet autoantibodies in the US is undertaken as part of programs to detect children, adolescents, and adults who are at higher risk of developing type 1 diabetes due to having a first-degree relative with type 1 diabetes or having a known high-risk HLA genotype.[1][82] However, up to 90% of people who develop type 1 diabetes are not part of at-risk groups.[82] Thus, screening programs within the general population are being considered. In 2023, Italy introduced nationwide screening for type 1 diabetes and celiac disease in the general population for people ages 1-17 years.[83] The ADA comments that general population-based screening programs may be feasible where high-quality, validated assays and resources for appropriate follow-up of results are available, with several countries considering making such testing part of standard care.[1]
Screening should be coupled with education and metabolic surveillance programs for those found to have multiple islet autoantibodies.[48] Patients should be referred for counseling about the risk of developing diabetes, diabetes symptoms, and DKA prevention. ISPAD guidelines state that for children, adolescents, and young adults with stage 2 disease, a review by an endocrinologist/diabetologist or diabetes educator every 6 months is recommended to reinforce understanding of the condition and expectations for progression.[48] They note that positive genetic and islet autoantibody screening results in children may be associated with parental stress, depressive symptoms, and diabetes-specific anxiety, as well as psychological distress in children, and recommend integration of psychosocial support for children and their caregivers into routine clinical visits.[48]
In addition to the provision of ongoing structured individualized education, consideration should be given for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes.[1] In the US, teplizumab, a monoclonal antibody, is approved in adults and children ≥8 years of ages with stage 2 type 1 diabetes to delay the onset of symptomatic disease (stage 3).[1] Trials with other drugs targeting 1) autoimmune responses, 2) antigen presentation, 3) glycemic dysregulation, and 4) beta-cell stress/dysfunction are underway.[48] See Primary prevention.
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