Abstract
Autoantibodies against pancreatic islets are strong predictors of Type 1 diabetes. When persistent β-cell autoantibodies against at least two autoantigens are detected, the probability of diabetes is extremely high, although the time period before disease development can vary from days up to more than 20 years. Insulin autoantibodies or antibodies specific to glutamate decarboxylase 65 enzyme are in most cases, the first autoantibodies to appear. Insulin autoantibodies typically emerge very early with a peak at the age of 1.5 years, whereas the onset of glutamic acid decarboxylase 65 antibody positivity has a more even distribution, peaking later in childhood. These differences in the timing of appearance suggest that different environmental factors might be involved in the initiation of β-cell autoimmunity beginning either already in infancy or later on. This should be taken into account in studies aimed at identifying environmental factors triggering islet cell-specific autoimmunity and also in the design of prevention trials.
Financial & competing interests disclosure
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Presence of serum autoantibodies (AABs) against various islet cell antigens is characteristic to Type 1 diabetes (T1D).
These AABs develop before clinical disease and the duration of this preclinical phase varies from a few weeks to decades.
Presence of AAB specificity is associated with a low probability of disease, but presence of multiple persistent AABs predicts diabetes with high probability.
If follow-up is frequent enough, one can, in most cases, detect the specific AAB initiating the autoimmunity.
Various initiating AAB specificities have distinct associations with age at process onset and with specific alleles in genes conferring T1D susceptibility.
These findings indicate heterogeneity in the disease process and in etiological factors.
It is important to take this heterogeneity into account when analyzing the effect of possible environmental factors on T1D risk and when prevention studies are planned and their results analyzed.