Given the increased understanding of the benefits of very early treatment for those with type 1 diabetes (T1D), including potentially preventive therapies, screening for T1D is now an important component of disease management.1 The need for early screening has only been heightened by the Food and Drug Administration (FDA) approval of teplizumab, the first drug shown to delay the onset of stage 3 T1D.2
Screening has several benefits, including the ability to:3
Reduce the trauma of an acute diagnosis for patients and families
Lower the incidence of diabetic ketoacidosis (DKA) at diagnosis in children with a genetic risk of T1D, who are then closely followed. Earlier identification can reduce the rate of DKA from 30–60% among patients who do not undergo early screening to less than 5% in screened populations.4 This is particularly important given that DKA at the onset of T1D is associated with increased mortality risk, longer hospitalizations, higher insulin requirements, shorter remission period, and worse glycemic control over time.3
Encourage caregivers to be more cognizant of clinical symptoms indicating T1D onset, leading to faster follow-up with healthcare providers
Provide time for patients and caregivers to learn about T1D and the lifestyle modifications required before clinical disease manifests
Identify patients for preventive therapies
Identify patients who may be eligible for clinical trials
Several large studies show that population-wide screening, including screening for genetic risk factors among newborns, is feasible and effective.5
As stated previously, development of islet autoantibodies precedes the symptoms and clinical diagnosis of T1D by months or even years, and this subclinical stage is what makes screening possible. Several islet autoantibodies have been described, but only a select few have been incorporated into screening.6 The American Diabetes Association (ADA) currently recommends screening for presymptomatic T1D with a blood test to measure 4 major T1D-associated islet autoantibodies (IAs): insulin (IAA), glutamic acid decarboxylase 65 (GAD65), insulinoma-associated antigen-2 (IA-2), and zinc transporter 8 (ZnT8).6
The ADA also recommends standardized IA tests for adults with diabetes who have phenotypic risk factors that overlap with those for T1D (eg, younger age at diagnosis, unintentional weight loss, ketoacidosis, or short time to insulin treatment).6 Screening for individuals of all ages who have a history of autoimmune diseases and/or family history of these conditions should also be considered. Most common autoimmune conditions associated with T1D risk are celiac disease, Hashimoto’s thyroiditis, Graves disease, but other autoimmune conditions should also be taken into account.6
Patients with multiple islet autoantibodies should be referred to a specialized center for further evaluation, including consideration for a clinical trial or approved therapy to potentially delay the development of clinical diabetes.6
Most United States-based guidelines recommend screening of individuals with family history or in the context of a research setting; however, considerations for screening in the general population are now being taken into account. For example, the guidelines from the International Society for Pediatric and Adolescent Diabetes (ISPAD) call for general-population and targeted screening, noting that screening of children between ages 2 and 6 may provide the optimal sensitivity. It is not clear how often screening should be done in high-risk children or when and how to screen in adults.7
Several screening programs are available at local and national levels. TrialNet is a national registry that provides in-home test kits and reports results in patient-friendly language, highlighting the implications.
In addition, several other local screening programs are available, including ASK, PLEDGE, and CASCADE.11 Screening is also available through clinical labs, and more information can be found under the Reading & Resources section.
As Table 1 shows, the results of the screening test determine an individual’s stage of diabetes.
Pooled data from prospective studies among children with multiple IAs identified an aggregate risk of progression to diabetes after 10 years of 69.7% (95% confidence interval [CI], 65.1–74.3) in children with a single IA compared with 0.4% in children with no IAs (95% CI, 0.2–0.6).9 Figure 1 shows the risk of clinical progression based on screening findings.
Children with a genetic risk of T1D in stage 1 with ≥2 autoantibodies, normoglycemia, and no symptoms have a 5-year risk of 44% of progressing to stage 3, a 10-year risk of 70%, and a lifetime risk of 100%. The risk for those in stage 2 with ≥2 autoantibodies and glucose intolerance or dysglycemia but no symptoms is 75% at 5 years and 100% over their lifetime.1,9
Table 2 highlights the recommended follow-up after screening. Clinical monitoring tools, including self-monitoring using fingersticks and home glucometer testing; glycated hemoglobin (HbA1c); oral glucose tolerance testing (OGTT); and continuous glucose monitors should also be used to assess T1D progression and help delay disease onset.10 More specific recommendations from Breakthrough T1D (formerly JDRF) about monitoring and follow-up, specifically for individuals who test positive for one islet autoantibody, as well as for those in stage 1 and stage 2, are currently in development, and will expand upon those reflected in Table 2.
Screening does have limitations. It cannot provide a definitive timeline to diagnosis. In addition, the results may cause increased anxiety and psychological distress in patients and families, although this can be addressed with education and counseling.12,13
There are also patient and family barriers, including transportation, fear, concern about a negative psychological effect based on the findings, and a lack of knowledge about the benefits of screening. Clinical barriers include clinician knowledge of screening and a reluctance to offer screening, given the distress it may cause patients and their families.14
Overcoming barriers to screening requires improved education for medical students and residents on the benefits of early screening and education for primary care physicians and endocrinologists on counseling patients and their families on the benefits of screening.
It is important that clinicians educate families about the importance of screening, using a shared decision-making model.
Clinicians have an important role to play in overcoming patient/family reluctance to screening. Here are some suggestions15–17:
