Twenty-Year Progression Rate to Clinical Onset According to Autoantibody Profile, Age, and HLA-DQ Genotype in a Registry-Based Group of Children and Adults With a First-Degree Relative With Type 1 Diabetes

Abstract

In single-autoAb relatives, the time to multiple-autoAb positivity increases with age and the absence of IAA and genotype. The majority of multiple-autoAb individuals progress to diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or ZnT8A, regardless of age, genotype, and number of autoAbs. These data may help to refine the risk stratification of presymptomatic type 1 diabetes.

Antibodies to oxidized insulin improve prediction of type 1 diabetes in children with positive standard islet autoantibodies

“…As reported by others, we also found an association between number of positive standard autoantibodies and risk of progression to diabetes . In the group of multiple autoantibody positive, oxPTM‐INS‐Ab testing refined risk by identifying a subgroup with a faster and greater risk of progression.…”

“…This is consistent with studies in T1D relatives. GADA was highly prevalent (74%) in first‐, second‐, or third‐degree T1D relatives from the TrialNet cohort and the most prevalent autoantibody in initially single positive relatives from the Belgian Diabetes Registry . However, we cannot exclude that subjects positive to GADA will develop diabetes at a later follow‐up not yet assessed in our study.…”

“…However, we cannot exclude that subjects positive to GADA will develop diabetes at a later follow‐up not yet assessed in our study. According to the report from the Belgian Diabetes Registry, relatives positive to GADA and IAA progressed more slowly than double autoantibody‐positive individuals carrying IA‐2A and/or ZnT8A . In a study by Knip and collaborators on subjects from the general population, 6 of 18 subjects (33%) developed diabetes after age of 20 (2 of 18 after age of 30), despite being islet autoantibody positive for up to 20 years .…”

Birth and coming of age of islet autoantibodies

“…Antibody combinations were subsequently used to select at‐risk relatives for clinical trials , and it is now well established that the diabetes risk associated with the presence of multiple islet autoantibodies (two or more of IAA, GADA, IA‐2A and ZnT8A) is markedly greater than the risk in people with a single autoantibody . A landmark study, that involved combined analysis of more than 13 000 individuals from three birth cohorts, demonstrated that almost all children with genetic susceptibility to type 1 diabetes who developed multiple islet autoantibodies progressed to diabetes (Fig.…”

Type 1 Diabetes: Disease Stratification

“…Faster rates of progression are observed with 3 or 4 versus 2 islet autoantibodies [25,70,71] . The presence of antibodies to IA-2 and ZnT8 as well as higher titers of antibody to Insulin and IA-2 are associated with a faster rate of progression [10,70,[72][73][74] . Islet autoantibody seroconversion at a young age is associated with a faster rate of progression [25] , and disease progression is also accelerated in children at stage 1 T1D with an increased BMI [75] and markedly accelerated in Hispanic children younger than 12 years of age who are overweight or obese [76] .…”