Objective
To investigate a novel autoantibody targeting the surface part of Zinc Transporter-8 molecule in patients with type 1 diabetes and at-risk population before type 1 diabetes.
Background Rationale
Type 1 diabetes results from the body’s immune system destroying the cells that produce insulin. Once enough of these cells are destroyed, high blood sugars result and patients need treatment with insulin injections. The incidence of type 1 diabetes has increased dramatically over the last 20 years, especially in children less than 5 years of age. Type 1 diabetes can be predicted years before overt clinical disease and many efforts are being taken to prevent diabetes onset. The mainstay of prediction depends upon detection of antibodies directed against proteins in insulin producing cells, termed islet autoantibodies. In our preliminary studies, we found in serum of new-onset patients with type 1 diabetes, a new islet autoantibody targeting the surface part of Zinc Transporter-8 (ZnT8) protein, which plays key roles in insulin secretion and normal function of insulin producing. Furthermore, we found that the new ZnT8 islet autoantibody (ZnT8ecA) was probably the first islet autoantibody to appear in developing to overt clinical diabetes. The work proposed in this grant application will expand these important findings to verify this new ZnT8ecA in patients with type 1 diabetes and at-risk population before type 1 diabetes.
Description of Project
Type 1 diabetes results from the body’s immune system destroying the cells that produce insulin. Once enough of these cells are destroyed, high blood sugars result and patients need treatment with insulin injections. Type 1 diabetes can be predicted years before overt clinical disease and many efforts are being taken to prevent diabetes onset. The mainstay of prediction depends upon detection of antibodies directed against proteins in insulin producing cells, termed islet autoantibodies. In our preliminary studies, we found in serum of new-onset patients with type 1 diabetes, a new islet autoantibody targeting the surface part of Zinc Transporter-8 (ZnT8) protein, which plays key roles in insulin secretion and normal function of insulin producing. Furthermore, we found that the new ZnT8 islet autoantibody (ZnT8ecA) was probably the first islet autoantibody to appear in developing to overt clinical diabetes. The work proposed in this grant application will expand these important findings to verify this new ZnT8ecA in patients with type 1 diabetes and at-risk population before type 1 diabetes. We will investigate in a large group of children with type 1 diabetes high-risk and closely followed-up from birth to determine if ZnT8ecA is the first islet autoantibody in disease progression, analyze the connection of ZnT8ecA with onset-ages and different types of type 1 diabetes, and further investigate the positivity of ZnT8ecA in children with relatively low-risk for type 1 diabetes. With this study ZnT8ecA may become a novel tool to predict and diagnose type 1 diabetes, and may help for preventive therapies of type 1 diabetes.
Anticipated Outcome
With this study we will verify the prevalence of ZnT8ecA in patients with type 1 diabetes and at-risk population before type 1 diabetes, and if ZnT8ecA is the first islet autoantibody in type 1 diabetes progression. ZnT8ecA may become a novel tool to predict and diagnose type 1 diabetes and may help for preventive therapies of type 1 diabetes.
Relevance to T1D
This proposed work will verify ZnT8ecA as a novel tool to improve prediction and diagnose of type 1 diabetes. Further study of ZnT8ecA may help for preventive therapies of type 1 diabetes.