Screening
Potential benefits of early identification of individuals at risk for autoimmune T1D
Screen early
Autoimmune T1D primarily results from the destruction of pancreatic beta cells due to an immune-mediated process, often triggered by environmental factors in individuals who are genetically predisposed.
The risk of developing autoimmune T1D can be assessed by considering family history, including the age of onset and sex of affected family members, along with profiling immunity and genetic markers.1
Risk factors and who should be screened
Screening for autoimmune T1D is helpful for early detection and management, particularly among high-risk individuals through family history or genetic or immunity markers. This includes first-degree relatives (FDRs), meaning individuals who have a parent, sibling, or child with autoimmune T1D.1,2
Only 5–10% of people living with autoimmune T1D have a family history of diabetes3
Islet autoantibodies in autoimmune T1D
Specific markers in the bloodstream are associated with the development of autoimmune T1D, which includes:
Some of these autoimmune T1D-related autoantibodies can be measured by diagnostic labs or clinics.1,4 Participants in research programs like TrialNet can access 4 autoantibodies from sources like the US.
Islet autoantibody screening can be performed using a small sample of capillary or venous blood. Several assay methods exist for measuring autoantibodies, and there is variation among methods and the performance of the tests.1,5
When combined with other forms of metabolic testing (glycated hemoglobin test), confirmed autoantibody results are essential for accurately determining the stage of autoimmune T1D.5
The DBS method collects blood samples obtained from finger or heel puncturing on a matrix paper, which is subsequently dried.6
Strengths and limitations
DBS sampling has been used for several decades and is comparable to venipuncture results. Sample collection, processing, transportation, and storage are simplified. As DBS samples can be mailed or shipped, the time in between collection and analysis can lead to degradation in quality and interfere with the results.6
The VBS draws venous blood through venipuncture and is analyzed in a lab, with advanced quality control measures.7
Strengths and limitations
This approach delivers more accurate results compared to capillary blood glucose testing, provided the lab adheres to industry standards. The downsides are that the procedure can be painful, it carries a risk of local tissue damage, and it is not ideal for frequent blood sampling.7
Salivary analysis is a non-invasive and convenient alternative to traditional diagnostic methods. Saliva, a complex fluid produced by the salivary glands in the mouth, contains a diverse range of biomolecules, electrolytes, and trace elements that could be used to diagnose an individual’s health.8
Strengths and limitations
The main advantage of salivary glucose monitoring is that it is non-invasive. Saliva can be collected easily and painlessly without the need for needles or lancets. However, there are some limitations: salivary glucose levels can vary due to factors like oral hygiene, oral health, diet, stress, and medication use. Additionally, the lack of a standardized testing method, including the need for further validation in sensitivity, specificity, and calibration, poses challenges. This method is also relatively new and tends to be more expensive.8
Find out more about autoantibody detection methods in autoimmune T1D
RBA uses radioisotopes to detect islet autoantibodies. It employs a radioactively labelled antigen to identify autoantibody binding, measuring the radioactivity to determine the presence and level of autoantibodies.5,9
Strengths and limitations
This method is considered the gold standard assay in autoimmune T1D in terms of accuracy for detecting autoantibodies. However, when applied to a population screening level, it is time-consuming, inefficient, and expensive. The majority of autoantibody positivity were found to be single autoantibodies, which were low risk with low affinity, which translated to minimal disease relevance.9
ECL is a modern, radiation-free technique that detects autoantibodies through light emission from a chemical reaction. It involves two labelled antigens binding to the autoantibody, creating a detectable signal.5,9
Strengths and limitations
ECL is known for its high sensitivity and specificity and can measure multiple autoantibody types in a single test, which has a strong application for population-wide screening. Limitations of ECL include the requirement for a special plate reader.9
ELISA detects autoantibodies using enzymes that attach to antibodies in the blood.5,9
Strengths and limitations
ELISA is used in commercial labs to detect ICA, GADA, IA-2A, and ZnT8A; however, the IAA tests are less sensitive. The sensitivity and specificity seen in known T1D samples are similar to RBA.10
ADAP can be performed on dried blood spot samples. It uses synthetic antigen-DNA conjugates that bind to autoantibodies, forming complexes that allow DNA ligation.5,9,10
Strengths and limitations
The autoantibody levels are quantifiable by qPCR. ADAP can measure multiple islet autoantibodies from a single sample and consistently achieves good sensitivity and specificity. However, as a newer method, further validation is required for non-diabetic population screening on IA-2A and ZnT8A.9
IFA is a cell-based assay that measures serum binding to human islet cells, detecting autoantibodies targeting multiple antigens. Unlike other methods that are specific to single autoantibodies, IFA can identify autoantibodies against several antigens.11
Strengths and limitations
The assay can identify multiple islet autoantibodies. However, ICA is time-consuming, it requires human pancreatic tissue, and it is difficult to yield quantitative results.11
Why screening matters
Early screening can identify individuals at risk before severe symptoms appear, allowing for earlier planning and monitoring. This proactive approach may help prevent critical illness and manage the condition more effectively from the outset.2
Incorporating screening for people at risk involves:2,5
- Referral to active screening facilities where and when applicable2,5
- Systematic testing: regularly test all FDRs and other high-risk individuals for autoimmune T1D-associated autoantibodies5
- Monitoring those who are in Stage 1 of the disease and referring to an endocrinologist if a positive diagnosis of Stage 2 disease is made
Current screening options available in Canada
Screening for autoimmune T1D risk in Canada is available primarily for relatives of people with autoimmune T1D. The main screening is through the TrialNet Research Program. This program offers autoimmune T1D risk screening for FDRs through a simple blood test that detects T1D-associated autoantibodies.12
Breakthrough T1D, in collaboration with Canadian Institutes of Health Research, also announced the launch of CanScreenT1D, a consortium that will explore the feasibility of general population screening for early-stage autoimmune T1D in Canada.13
Monitoring and referral process
For individuals who test positive for autoimmune T1D-associated autoantibodies:
- Those in the early stages can be closely monitored for progression. This involves regular follow-ups.1,14
- Referral to an endocrinologist or genetic screening, where applicable, is recommended.14
ADAP=antibody detection by agglutination-PCR; ECL=electrochemiluminescence; ELISA=enzyme-linked immunosorbent assay; FDRs=first-degree relatives; GADA=glutamic acid decarboxylase autoantibody; IA-2As=insulinoma associated-2 antibody; IAA=insulin autoantibody; ICA=islet-cell antibody; IFA=indirect fluorescent antibody; RBA=radiobinding assay; ZnT8A=zinc transporter type 8 autoantibody.
- Ekoe J-M, et al. Screening for Diabetes in Adults. Can J Diabetes 2018; 42:S16–9.
- TrialNet. TrialNet Recommendations for Clinicians. Available at: https://www.trialnet.org/healthcare-providers. Accessed July 12, 2024.
- Punthakee Z, et al. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes 2018;42:S10–5.
- Phillip M, et al. Consensus Guidance for Monitoring Individuals With Islet Autoantibody-Positive Pre-Stage 3 Type 1 Diabetes. Diabetes Care 2024 Jun 24:dci240042. doi: 10.2337/dci24-0042. Online ahead of print.
- Sims EK, et al. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes 2022;71:610–23.
- Mastronardi CA, et al. The use of dried blood spot sampling for the measurement of HbA1c: a cross-sectional study. BMC Clin Pathol 2015;15:3.
- Mathew TK, et al. Blood Glucose Monitoring. [Updated 2023 Apr 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555976.
- Ko A and Liao C. Salivary glucose measurement: A holy ground for next generation of non-invasive diabetic monitoring. Hybrid Advances 2023;3:100052.
- Jia X and Yu L. Effective assay technologies fit for large-scale population screening of type 1 diabetes. Front Clin Diabetes Health 2023;23:3:1034698.
- Ross E and Altimus C. Type 1 Diabetes Autoantibody Screening: A Roadmap for Pediatric Policy Implementation. Milken Institute 2021:1–41.
- Kawasaki E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int J Mol Sci 2023;24(12):10012.
- TrialNet. Pathway to Prevention. Available at: https://www.trialnet.org/our-research/risk-screening. Accessed July 12, 2024.
- JDRF. CanScreenT1D: Screening Research Consortium in Canada Announced. Available at: https://jdrf.ca/canscreent1d-screening-research-consortium-in-canada-announced/. Accessed July 12, 2024.
- Besser REJ, et al. ISPAD clinical practice consensus guidelines 2022: Stages of type 1 diabetes in children and adolescents. Pediatr Diabetes 2022;23(8):1175–87.
