A single screening at age 10 was more likely to be predictive for type 1 diabetes by the age of 18 years in high risk children compared to screening them twice, suggests a study published in The Lancet Child & Adolescent Health.¹

Data of 1890 children from the Diabetes Prediction and Prevention study (DIPP), BABYDIAB study and the Diabetes Autoimmunity Study in the Young (DAISY) and the Diabetes Evaluation in Washington study (DEW-IT) was examined. A family history of type 1 diabetes was positive in 59.2% of children. Those who had been diagnosed with type 1 diabetes before the age of 10 years were not included in the study group. The participants were tested for three islet cell autoantibodies including insulin autoantibody (IAA),  glutamic acid decarboxylase autoantibody (GADA) and insulinoma-associated protein 2 autoantibody (IA2A) on each follow-up visit. The objective of the study was to evaluate if screening for islet cell autoantibodies could predict the onset of type 1 diabetes in at-risk adolescents aged 10-18 years.

The DIPP study was conducted in Finland to determine the feasibility of genetic and immunological prediction of type I diabetes. BABYDIAB was a German study examining the natural history of type 1 diabetes. DAISY studies from the United States were about newborn screening for genes associated with insulin-dependent diabetes mellitus (IDDM); EW-IT, another US study examined newborns at high genetic risk of type 1 diabetes.

Over the median follow-up of 18.3 years, 442 (23.4%) tested positive for at least one islet cell autoantibody at a median age of 7.1 years; of these, 262 (13.9%) went on to develop type 1 diabetes at a median age of 12.6 years. “Time from seroconversion to diabetes diagnosis increased by 0.64 years for each 1-year increment of diagnosis age,” observed the authors. Among the 227 participants who were autoantibody positive, the median interval between the last prediagnostic sample and diagnosis was 0.3 years. This median interval was 6.8 years among the 35 subjects who were negative for autoantibodies.

When adolescents were screened just once at the age of 10 years, the sensitivity of the single screening was 90% with a positive predictive value (PPV) of 66% for diabetes. When they were screened at age of 10 years and again at 14 years, the sensitivity of screening increased slightly to 93%; however, the PPV declined to 55%.

In an article published in Nature, Kwon et al write, “development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict”.²

Undiagnosed and therefore untreated type 1 diabetes can result in diabetic ketoacidosis, which requires prompt management. Early diagnosis, especially in children at high risk of developing type 1 diabetes, will help prevent this potentially fatal complication of type 1 diabetes. Screening allows diagnosis before clinical disease develops.

Last year in November, the US FDA approved the injectable monoclonal antibody teplizumab-mzwv as the first preventive treatment for type 1 diabetes “to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes”.³ Teplizumab is an anti-CD3 antibody, which modifies CD8+ T lymphocytes, major cells involved in the pathogenesis of type 1 diabetes. This also highlights the significance of screening children at high risk of type 1 diabetes for timely  intervention with this monoclonal antibody.

References

1. Mohamed Ghalwash, et al; Type 1 Diabetes Intelligence Study Group. Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort study. Lancet Child Adolesc Health. 2023 Jan 18;S2352-4642(22)00350-9. doi: 10.1016/S2352-4642(22)00350-9.
2. Kwon BC, et al; T1DI Study Group. Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories. Nat Commun. 2022 Mar 21;13(1):1514. doi: 10.1038/s41467-022-28909-1.
3. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-can-delay-onset-type-1-diabetes, November 17, 2022. Accessed on Feb.2, 2023.