Progression of Type 1 Diabetes

The development of type 1 diabetes may take only a few months, but also many years. A combination of specific risk gene variants, the early appearance of autoantibodies against the insulinoma-­associated antigen-2 (IA-2A) and a birth by cesarean section seem to facilitate a rapid progression of the autoimmune disease.

Type 1 diabetes is an autoimmune disease. Just how quickly the autoimmune process progresses and type 1 diabetes develops appears to be dependent on an interplay of genetic and environmental factors. Scientists of the Institute of Diabetes Research have partly succeeded in elucidating relevant gene combinations.

The researchers led by Peter Achenbach and Anette-Gabriele Ziegler analyzed data of the BABYDIAB study. This prospective cohort study includes participants from birth on who have at least one relative with type 1 diabetes. Two extreme groups were compared with each other over an observation period of 20 years: the group of slow progressors – children who developed type 1 diabetes at the earliest ten years after the first appearance of autoantibodies – and the group of rapid progressors – children who developed the disease at the latest three years after their first appearance.

Basically, as far as demographic factors were concerned, the children were comparable. With respect to environmental factors they differed only in the factors spontaneous delivery or cesarean section. While half of the rapid progressors were delivered by cesarean section, this was the case with only every sixth slow progressor. The greatest immunological difference was seen in the development of autoantibodies against insulinoma-associated antigen-2 (IA-2A), which in general indicate a high diabetes risk: The slow progressors showed a delayed development of IA-2A. Characteristic of the rapid progressors was a higher percentage of risk variants of genes involved in immune regulation. These gene variants are individually connected to a relatively small increased risk of disease. However, if they occur in certain combinations, this seems to favor an early onset of the disease. This is especially true for genes encoding for interleukin-2 (IL2), the alpha subunit of the IL-2 receptor (CD25), interleukin-10 and interferon-induced IFIH1 helicase. In contrast, no difference could be found regarding the HLA (human leucocyte antigen) gene variants that pose the greatest risk for type 1 diabetes.

Type 1 diabetes is the most common metabolic disease in childhood and adolescence. The body’s immune system attacks the insulin-producing cells in the pancreas and destroys them. This autoimmunity, which underlies the metabolic disorder, is based on a genetic predisposition and is influenced by environmental factors. Type 1 diabetes can occur at any age. The peak incidence is during puberty from age 10 to 15 years.