medwireNews: Although a rare occurrence, non-maintenance of two or more type 1 diabetes autoantibodies may be associated with a reduced risk for progression to diabetes, show data presented at the ADA 79th Scientific Sessions in San Francisco, California, USA.
Michelle So, from the Benaroya Research Institute in Seattle, Washington, USA, explained that the majority of studies have reported on the association between diabetes risk and the loss of single autoantibodies, but clinical trials to delay or prevent disease progression often enroll people with two autoantibodies because they progress to diabetes faster.
So and team therefore investigated the frequency of non-maintenance in 3284 participants with multiple autoantibodies screened through the TrialNet Pathway to Prevention Study.
During a mean follow-up of 2.2 years, 96.1% maintained their autoantibody status, while the remaining 3.9% were non-maintainers, defined as having a reduction in autoantibody numbers to below two on a least two occasions within 12 months of confirmed multiple autoantibody positive status.
So reported that over 12 months, non-maintainers had a significantly lower rate of progression to stage 3 type 1 diabetes than maintainers, with cumulative incidence at approximately 75% versus 42%. The difference between the two groups was greatest among the younger participants (aged 0–8 and 9–12 years) and was much smaller for teenagers and adults.
She also looked at how non-maintainers differed from maintainers and found that non-maintenance was associated with a significantly lower autoantibody number at the time of confirmed multiple autoantibody positive status (2.1 vs 3.1) and a significantly lower frequency of MIAA, IA2A, and ZnT8A, but not ICA or GADA autoantibodies.
In addition, non-maintainers had lower autoantibody titers for ICA, IA2A, and ZnT8A, “suggesting that titer was playing a role in the disappearance of these antibodies,” So remarked.
Finally, non-maintainers were, on average, significantly older than maintainers (19.2 vs 13.1 years) but the two groups did not differ in terms of gender, BMI, oral glucose tolerance test results, and high risk or protective HLA status.
Discussing the limitations of the study, So pointed out that it only included participants in families already affected by clinical (stage 3) type 1 diabetes. Therefore, the proportion of non-maintainers may differ in the general population, she said.
And she concluded: “Multiple autoantibody non-maintainers have a slower progression to stage [3] type 1 diabetes [than maintainers] but low numbers mean this is unlikely to affect trial outcome and doesn’t warrant changes to recruitment strategies at this stage.
“In addition, although there are statistically significant differences in baseline characteristics between the two groups, there is really no one characteristic that could be used to identify these non-maintainers.
“This suggests that there are unknown mechanisms that can lead to immune remission in some individuals.”
By Laura Cowen
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79th ADA Scientific Sessions; San Francisco, California, USA: 7–11 June 2019