New Markers Found for Early Detection of Type 1 Diabetes

The study provided indications of an early onset of the disease when specific antibodies in the blood and specific variants of the associated zinc transporter are present in the genome. These high-risk individuals require especially careful monitoring.

The research was performed under the direction of Prof. Dr. Anette Ziegler, scientists of the Diabetes Research Group at Helmholtz Zentrum München (Germany) and Technische Universität München (Germany).

Worldwide, the number of children who develop type 1 diabetes is increasing. In Germany, approximately 11,000 children are affected. On average, they are eight and a half years old when they are diagnosed with the disease. However, already at this age many children show severe metabolic decompensation. Successful prevention strategies and detailed screening can prevent this.

Prof. Dr. Anette Ziegler and Dr. Peter Achenbach, from Helmholtz Zentrum München and Technische Universität München in cooperation with Prof. Dr. Ezio Bonifacio of Technische Universität Dresden, have developed a new approach to improve and extend risk screening. "Acute severe complications such as diabetic coma at disease onset can thus be avoided in the majority of the children,” Dr. Peter Achenbach explained. The scientists evaluated the data of 1,633 children who had at least one type 1 diabetic parent. These children's risk for diabetes was elevated in comparison with children who had no family history of diabetes.

Genetic factors play a considerable role in the development of type 1 diabetes. The scientists were able to show that specific variants of the zinc transporter gene SLC30A8 influence the risk for diabetes. The body needs this gene in order to produce ZnT8. This protein influences the zinc transport into the beta cells and plays a crucial role in their maturation and thus also in insulin secretion.

Beta cells of the islets of Langerhans in the pancreas secrete the critically important insulin. Already before the onset of type 1 diabetes the body's own immune system destroys the beta cells. If this destruction exceeds a certain threshold, the disease becomes evident: The insulin deficiency leads to various metabolic disturbances, including elevated blood glucose levels.

"Autoantibodies to ZnT8 in combination with a specific variant of the zinc transporter gene were associated with an elevated diabetes risk,” said Dr. Peter Achenbach, from the Institute for Diabetes Research at Helmholtz Zentrum München. "Eighty-one percent of these children with ZnT8 antibodies developed diabetes mellitus.” An increased diabetes risk has long been associated with the islet autoantibodies. These include the autoantibodies to insulin (IAA), islet cell antibodies to the enzyme glutamate decarboxylase (GADA) and to tyrosine phosphatases (IA-2A and IA-2ß).

"Autoantibodies to ZnT8 are an additional important marker for the progression of diabetes--especially in children who are already developing islet autoantibodies,” said Dr. Thomas Illig, from the Institute of Epidemiology at Helmholtz Zentrum München. A differentiated analysis of all autoantibodies allows the prognosis of how fast the disease will become manifest. According to Dr. Illig, the rule of thumb is: The larger the number of different kinds of autoantibodies, the higher the risk for diabetes, and the younger the child with autoantibodies, the earlier disease onset will be.

The study was published in the September 2009 issue of the journal Diabetolgia
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