Persistence of islet autoantibodies after diagnosis in type 1 diabetes

Abstract

The presence of islet autoantibodies remains a reliable biomarker to identify individuals at high risk of developing type 1 diabetes. As such, these autoantibodies play a pivotal role in understanding the prodrome of diabetes and selecting individuals for both prevention and intervention clinical trials. Over the last few decades, studies have sought to investigate autoantibody prevalence after diabetes onset to better understand ongoing islet autoimmunity; however, many findings are contradictory, and little is known about factors that may influence autoantibody persistence. Generally, glutamate decarboxylase autoantibodies (GADAs) are the most prevalent autoantibodies after diagnosis, particularly in adults, whilst zinc transporter 8 autoantibodies (ZnT8A) prevalence declines more rapidly. However, when studies with islet autoantibody data at diagnosis are considered, it becomes clear that overall islet antigen‐2 autoantibodies (IA‐2A) tend to persist for longer than GADA or ZnT8A. In this review, we assess the major studies that have contributed to our understanding of autoantibody persistence after diabetes onset and what factors affect this. Islet autoantibodies may provide biomarkers for long‐term β‐cell function and insights into how to prevent ongoing islet autoimmunity but larger studies collecting samples at and decades after diabetes onset are required to leverage the information they could provide.

The relationship between islet autoantibody status and the genetic risk of type 1 diabetes in adult-onset type 1 diabetes

“…Furthermore, IAA prevalence is known to decrease with increasing age at diagnosis, so undetected IAA would not have explained the increasing prevalence of negative autoantibodies with age [ 48 ]. It is possible that autoantibody status may change over time [ 50 , 51 ], but this is unlikely to explain the reduction in genetic predisposition to type 1 diabetes in autoantibody-negative adults given the lack of difference in autoantibody-positive and antibody-negative children and the lack of an interaction between T1DGRS and number of positive autoantibodies.…”

Recent Advances of Integrative Bio-Omics Technologies to Improve Type 1 Diabetes (T1D) Care

“…Additionally, Gan et al assessed the quantity of specific biomarkers related to each demographic group through proteomic analysis [7]. The most common traditional biomarkers are islet autoantibodies including IA-2A, GAD, ZnT8Ab autoantibodies [45]. The later-age onset of T1D is related to characteristic levels of GADA, thyroid peroxidase (TPOA), and gastric parietal cell antibodies (PCA) in the individual.…”

Distribution of autoantibodies to insulinoma‐associated antigen‐2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide, multicentre, cross‐sectional study

“…These findings demonstrate that GADA is a valuable autoantibody for differentiating LAD from T2D. However, GADA is insufficient to identify LAD given that IA‐2A prevalence time tends to be longer than the prevalence time of GADA and zinc transporter 8 autoantibody (ZnT8A) 2 . In addition, IA‐2A could be the only independent predictor of a more rapid progression to diabetes 18 .…”

“…Characterised by autoimmune destruction of islet beta cells and insulin dependence, type 1 diabetes (T1D) is generally considered to be a chronic autoimmune disease with positivity for at least one islet autoantibody 1,2 . Latent autoimmune diabetes (LAD) is a slowly progressive form of diabetes that includes latent autoimmune diabetes in the young (LADY) and latent autoimmune diabetes in adults (LADA) according to age at onset 3–5 .…”