Objective
The objective of this study is to explore the association of immune response changes with clinical measurements to better understand the different pathogenic mechanisms underlying type 1 diabetes and open the possibility for prediction and prevention of the disease.
Background Rationale
Type 1 diabetes (T1D) is the most common chronic endocrine disorder in children, characterized by insulin deficiency and subsequent hyperglycemia due to the autoimmune destruction of insulin-producing pancreatic beta cells. It has severe long-term complications and results in a substantial burden on families and the healthcare system due to lifelong exogenous insulin treatment and monitoring. The appearance of islet-specific autoantibodies in the serum (so-called seroconversion) is the earliest and only indicator to predict T1D progression before its symptomatic onset. Considerable heterogeneity in the rate of progression to clinical T1D, depending on factors such as the age of seroconversion and the type of first-appearing autoantibody, has been observed. Thus, the increasing knowledge in the pathogenesis of T1D leads to recognizing different disease pathways, or endotypes, behind one clinical disease. Identifying changes in circulating immune cells associated with the type of autoantibody that appears first would contribute to our understanding of the different pathogenic mechanisms underlying T1D and provide a possibility for disease prediction and prevention. Next, newly diagnosed patients with T1D are highly heterogeneous in the rate of disease progression. The large variation in T1D across individuals hampers the understanding of disease pathogenesis and the development of effective therapies. Clearly, the ability to classify patients and predict disease progression would enable effective clinical trials and more personalized therapies.
Description of Project
Type 1 diabetes (T1D) is an autoimmune disease in which the immune system attacks and destroys the beta cells in the pancreas that make insulin. This is one of the most common chronic conditions in children. The disease has long-term complications and results in a substantial burden on families and the healthcare system. Within the past few decades, there has been an increase in the incidence rate of T1D worldwide. Additionally, considerable heterogeneity in the rate of progression to clinical T1D, as well as in the post-onset insulin secretion decline, has been observed. Thus, the increasing knowledge in the pathogenesis of T1D has led to the recognition of different disease pathways, or endotypes, behind one clinical phenotype. The large variation in T1D across individuals hampers the understanding of disease pathogenesis and the development of effective therapies. Understanding the different pathogenic mechanisms underlying T1D could lead to disease prediction and prevention. This study aims to explore changes in immune response in newly diagnosed T1D patients and unaffected family members to predict disease progression and better understand the disease pathogenesis. The results may provide biomarkers for predicting disease progression and help classify patients into different progressor groups, leading to more personalized therapies and the development of effective treatments for T1D.
Anticipated Outcome
We expect to identify changes in immune response associated with disease progression in newly diagnosed T1D patients as well as their unaffected family members associated with different autoantibody profiles. These results may provide novel candidates to be considered as potential biomarkers for disease prediction.
Relevance to T1D
The results of our study may provide novel biomarkers to predict the rate of T1D progression, which will be helpful in designing new effective therapies to cure the disease. The results could help in classifying at-risk individuals and further developing therapies aimed at preventing or arresting disease progression.