Need to identify risk of developing autoimmune type 1 diabetes? Test for autoantibodies!

Key takeaway

Why screen for autoantibodies?

Autoimmune T1D is associated with the appearance of autoantibodies many months or years before symptom onset.¹ Decline in beta-cell function occurs in three distinct stages and by the time clinical symptoms manifest, significant beta-cell loss has typically occurred.^1,2 Screening for autoantibodies is important for early detection of beta-cell destruction and provides patients/caregivers with opportunity to access healthcare providers to help them prepare and develop skills for better management of T1D.^2,5,6 The autoantibodies detected in autoimmune T1D include:^1,2

• Glutamic acid decarboxylase antibodies (GADA)
• Insulinoma-associated-2 autoantibodies (IA-2A)
• Insulin autoantibodies (IAA)
• Zinc transporter 8 autoantibodies (ZnT8A)               

Stages of autoimmune T1D depicting progressing beta-cell function decline²

How the presence of islet autoantibody determines risk of T1D?

The number of detectable autoantibodies through screening correlates with risk of developing autoimmune T1D.^2,6 The majority of individuals with a single autoantibody do not progress to autoimmune T1D.⁷ However, presence of two or more autoantibodies increases the risk of progression to clinical T1D to 70% over 10 years and 100% over lifetime.⁶

Risk of progression to autoimmune T1D after seroconversion to islet autoantibody positivity⁶

Who should be screened for islet autoantibodies?

Individuals with a family history of T1D are at greater risk of developing the disease, with up to a 15-fold increased risk if a first-degree relative has T1D.⁵ Additionally, individuals with certain other associated autoimmune diseases (e.g., celiac disease and autoimmune thyroiditis) and adults with abnormal glucose levels with a low BMI (<25 kg/m²) or aged <35 years are also likely to develop T1D.^9,10. 

What is right age for screening for autoimmune T1D?

Although T1D can manifest at any age, it most commonly occurs in children, teenagers, or young adults.^1,11 Autoantibodies often emerge before the age of 6, even in cases where T1D is diagnosed much later in childhood. Screening for islet autoantibodies at ages of 2 and 6 has proven to be sensitive and efficient in predicting autoimmune T1D.¹²

What are the benefits of screening for autoimmune T1D?

Screening shows that approximately 95% of relatives of individuals with T1D test negative for autoantibodies, which can provide reassurance, especially to families with an affected member.⁵

In individual who test positive for autoantibodies, screening leads to early detection of autoimmune T1D, which in turn: ⁶

• Can prevent diabetes ketoacidosis, a life-threatening complication of diabetes.
• Provide preparation time to patients and caregivers to develop skills to manage T1D.
• Enable access to medical care to provide ongoing education and monitoring.

References

1. Katsarou A, Gudbjörnsdottir S, Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017;3:17016.
2. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: A scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964-1974.
3. Tiberti C, Yu L, Lucantoni F, et al. Detection of four diabetes specific autoantibodies in a single radioimmunoassay: an innovative high-throughput approach for autoimmune diabetes screening. Clin Exp Immunol. 2011;166(3):317-324. ​
4. Cortez FJ and Gebhart D, Robinson PV, et al. Sensitive detection of multiple islet autoantibodies I type 1 diabetes using small sample volumes by agglutination-PCR. PLoS One. 2020;15(11):e0242049.
5. Sims EK, Besser REJ, Dayan C, et al; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for type 1 diabetes in the general population: A status report and perspective. Diabetes. 2022;71(4):610-623.
6. Simmons KM and Sims EK. Screening and prevention of type 1 diabetes: Where are we? J Clin Endocrinol Metab. 2023;108(12):3067-3079.
7. DiMeglio LA, Evans-Molina C and Oram RA. Type 1 diabetes. Lancet. 2018;391(10138):2449–2462.  
8. Ziegler AG and Nepom GT. Prediction and pathogenesis in type 1 diabetes. Immunity. 2010;32(4):468-78.
9. Makimattila S, Harjutsalo V, Forsblom C, et al. Every fifth individual with type 1 diabetes suffers from an additional autoimmune disease: a Finnish nationwide study. Diabetes Care. 2020;43(5):1041-1047.
10. American Diabetes Association. Standards of care in diabetes—2024. Diabetes Care. 2024;47(suppl 1):S1-S321.
11. You W-P and Henneberg M. Type 1 diabetes prevalence increasing globally and regionally: The role of natural selection and life expectancy at birth. BMJ Open Diabetes Research and Care. 2016;4:e000161.
12. Ghalwash M, Dunne JL, Lundgren M, et al. Two-age islet-autoantibody screening for childhood type 1 diabetes: a prospective cohort study. Lancet Diabetes Endocrinol. 2022;10(8):589-596.
13. Greenbaum CJ. A Key to T1D Prevention: Screening and monitoring relatives as part of clinical care. Diabetes. 2021;70:1029–1037.