medwireNews: Islet autoantibody screening for early-stage type 1 diabetes in children is feasible in the general population, the Fr1da study investigators have found.
They report in JAMA that this approach was “efficient and sensitive,” identifying 81% of the 260 children who progressed to clinical stage 3 disease (hyperglycaemia with or without symptoms) during follow-up after an initial early-stage diagnosis.
Moreover, the rate of progression to stage 3 type 1 diabetes did not significantly differ between children with and without a first-degree relative with type 1 diabetes. And the timing of progression between each of the disease stages was consistent.
“These findings inform screening programs to diagnose early-stage type 1 diabetes in children and the design of trials aimed at delaying clinical type 1 diabetes”, write Anette-Gabriele Ziegler (Institute of Diabetes Research, Helmholtz Munich, Germany) and co-authors.
Blood samples from 220,476 children (median age 3.1 years, 51.3% boys) living in Bavaria were screened for the presence of two or more autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen (IA)-2A, or zinc transporter 8 (ZnT8A).
Initially, the 716 participating primary care paediatricians collected one sample from children aged 1.8 to 6.0 years and in March 2019, the age range was extended to 11.0 years and two samples were collected, the researchers say.
Of 219,951 participants with a successful sample, 0.33% were positive for two or more islet autoantibodies, including 33 patients who were immediately diagnosed with stage 3 type 1 diabetes and excluded from the study.
In total, 590 children tested positive at first screening for presymptomatic type 1 diabetes, 366 of whom underwent metabolic staging based on oral glucose tolerance tests and glycated haemoglobin, revealing that 74.5% had stage 1 disease, 17.7% stage 2 and 3.7% stage 3, while 4.1% could not be classified. These rates translated to an adjusted population frequency of stage 1 and 2 type 1 diabetes of 0.23% and 0.06%, respectively.
And among 11,726 children without early disease who were retested after a median of 3.3 years, 0.30% were positive for at least two islet autoantibodies, and 0.25% had a confirmed diagnosis of early-stage type 1 diabetes, giving an adjusted population prevalence of 0.27%, the researchers continue.
After a median 5.7 years of follow-up, 212 children with an early-stage diagnosis at first screening and five with an early-stage diagnosis at second screening had developed stage 3 type 1 diabetes, as had 43 participants without an early-stage diagnosis.
The 5-year progression rate from early-stage type 1 diabetes to stage 3 disease was 36.2%, affecting a comparable 41.4% of children with and 35.3% of children without a first-degree family history of disease.
Specific combinations of autoantibodies were significant predictors of progression in multivariable analysis, the researchers add, with progression most common in children who were positive for IA-2A, IAA, and ZnT8A but not GADA (73.9%).
The researchers also remark that it was “notable and unexpected” to find that the time to progression from stage 1 to stage 2 disease was comparable to that from stage 2 to stage 3 disease, taking a median of approximately 3 years in both cases.
“Although factors such as infection have been associated with initiation or an acceleration of disease, these data suggest that mechanisms driving the disease after its initiation may be operating relatively constantly throughout early-stage disease, rather than accelerating solely near the time of clinical diagnosis”, they suggest.
“This finding carries implications for therapeutic development, particularly in individuals with stage 1 type 1 diabetes, who comprise most early-stage diagnoses.”
In an accompanying editorial, Jamie Felton and Emily Sims, both from Indiana University School of Medicine in Indianapolis, USA, say the Fr1da findings “demonstrate the feasibility of detecting type 1 diabetes in a non-targeted population, but also highlight an efficient and effective system that supports diagnosis, follow-up, and treatment”.
Describing the study as a “pivotal step forward”, the editorialists conclude that “[t]he challenge now is no longer whether we can identify individuals at risk, but how to act on that knowledge to alter disease trajectory.”
By Lynda Williams
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