Diesease progression possible with presence of two or more autoantibodies…
Autoimmune type 2 diabetes is preceded by the appearance of islet insulin autoantibodies: GAD autoantibodies (GADAs), insulinoma-associated protein 2 autoantibodies (IA-2AS), and zinc transporter 8 autoantibodies. Previous studies show that diabetes will develop within 10 years in 27-40% of children with two or more of the autoantibodies present. However, the timeline of the progression toward diabetes is not fully understood.
The Environmental Determinants of Diabetes in the Young (TEDDY) is a multicenter observational study designed to map the predicating factors leading to type 1 diabetes from birth to the age of fifteen and identify the precipitating exposures. The study observed 8,503 children who were found to be at increased risk for autoimmune diabetes through a screening for diabetes susceptibility HLA-DR/DQ genotypes at sites in Sweden, Finland, Germany, Colorado, Washington, Florida, and Georgia. IAAs, GADAs, and IA-2As were measured every 3 months until four years of age and every six months thereafter. If the children were found positive for any particular autoantibody, they were measured every three months.
After a follow-up time of five years, persistent confirmed islet autoimmunity developed in 577 children. Furthermore, 164 of the children progressed to diabetes. Of the 577 children found to have autoantibodies, 61% had multiple autoantibodies, including 32% with all three autoantibodies present, 17% with IAAs and GADAs, 7% with IAAs and IA-2As, and 5% with GADAs and IA-2As. Of those with only one autoantibody present, 22% had GADAs, 16% had IAAs, and 1% had IA-2As. The age of seroconversion was significantly younger in those children who progressed to diabetes as compared with those who did not (1.3 vs. 2.5 years, P <0.0001). Of those children who progressed to diabetes, 88% had multiple autoantibodies, with 54% having all three antibodies. Progression to diabetes utilizing a Kaplan-Meier life table analysis showed that the cumulative incidence of diabetes within five years of seroconversion increased with the number of positive autoantibodies. There was no significant difference between children expressing two or three autoantibodies (P =0.08).
The researchers concluded that most of the children who progressed to diabetes had two or more autoantibodies present at a young age (average 1.3 years). In those children with positive autoantibodies, progression to diabetes was influenced by family history, but not necessarily the presence of the high-risk HLA-DR3-DQ2/DR4-DQ8 genotype.
- Children found to have two or more autoantibodies IAA, GADA, IA-2A present, are at increased risk of developing diabetes.
- Those children found to have these autoantibodies present at a younger age are at increased risk of developing diabetes.
- Special attention should be given to those children with autoantibodies present and a positive familial history of diabetes.
Steck AK. Predictors of Progression from the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care.May 2015. 38(5)808-13.