Objective
Overall Objective:
This project aims to explore the different forms of Type 1 diabetes (T1D) by analyzing a rich dataset from the German Diabetes Study, which has been recruiting and comprehensively characterizing persons with recently diagnosed T1D since 2005. In preliminary analyses, we have found 3 distinct metabolic groups of T1D. The current project aims to further characterize these groups by performing genetic investigations with high-resolution sequencing. We will also derive measures of genetic T1D and type 2 diabetes (T2D) risk for every participant. This information will lead to the identification of groups with distinct disease profiles, progression and risks of complications. Some of these groups could especially benefit from specific early treatments that could relevantly delay or stop the decay of insulin producing cells.
Specific Aims:
1. Identify New Clusters of T1D: We uncovered new subtypes of adult-onset T1D by examining detailed glycemic and lipid data from the German Diabetes Study. We will use proteomic data and newly generated genetic data to reveal specific profiles for these subtypes. Additionally, we will extend our analysis by adding these proteomic and genetic data, alongside key T1D-related immune markers to identify novel clusters from a more comprehensive set of biologic markers defining the condition. We will also compare T1D subtypes with those who do not have diabetes or who have Type 2 diabetes from the same study group.
2. Validate Findings in a Larger Population: We will test the T1D subtypes identified in the first aim using data from the UK Biobank, which includes a large and diverse group of participants. We will link these subtypes to real-world health outcomes, including diabetes complications and medication use. This will help us understand how these subtypes differ from other types of diabetes and how they are linked to long-term health outcomes.
Background Rationale
Type 1 diabetes (T1D) has traditionally been understood as a condition primarily affecting children, adolescents, or young adults, characterized by the autoimmune destruction of pancreatic beta cells, ultimately leading to absolute insulin deficiency. However, recent evidence has significantly broadened our understanding of the disease, showing that T1D can manifest at any age, including middle and later adulthood. Diagnosing T1D in adults is complex due to its similarity to type 2 diabetes (T2D), especially in older individuals who often exhibit characteristics of the other condition such as insulin resistance. This can lead to frequent misdiagnosis, complicating treatment and management. Moreover, T1D is increasingly recognized as a heterogeneous disease, with significant variation in clinical presentation, genetic markers, and disease progression among individuals. Our research aims to address this problem by using detailed phenotypic, genetic and protein data to identify specific subtypes of T1D, which could lead to more personalized and effective treatments.
Description of Project
Type 1 diabetes (T1D) is a complex autoimmune disease that has traditionally been thought to primarily affect children and young adults. However, recent research shows that T1D can occur at any age, challenging previous knowledge. Diagnosing T1D in adults is difficult because its symptoms often resemble those of type 2 diabetes (T2D), which is more common in older adults. Misdiagnosis can affect treatment decisions and leading to suboptimal management.
This research aims to improve the understanding and management of T1D by exploring the differences within the disease. We will use advanced techniques such as genetic analysis and protein studies to identify distinct subtypes of T1D. By analyzing data from the German Diabetes Study, which includes comprehensively characterized individuals recently diagnosed with T1D, we aim to uncover new insights into the different forms of T1D.
Our goal is to develop a new model that can accurately identify these subtypes, leading to more personalized treatment possibilites. This could help tailor treatments to the specific needs of each patient, improving their quality of life. We will also validate our findings by testing them in a large, diverse group of people from the UK Biobank, ensuring that our results are applicable to a wide range of populations.
Anticipated Outcome
We anticipate that our research will uncover new subtypes of Type 1 diabetes (T1D), particularly in adults. By identifying these subtypes, we hope to improve the diagnosis and treatment of T1D, making it possible to tailor treatments to the specific needs of each patient. This could lead to better disease outcomes, such as improved blood glucose control and a lower risk of complications.
Relevance to T1D
This research is directly relevant to Type 1 diabetes (T1D) because it seeks to improve the way the disease is diagnosed and treated. By identifying different subtypes of T1D in adults, we can potentially develop more personalized treatment plans. This approach could help reduce the risk of complications and improve quality of life for people living with T1D by providing a more tailor-made treatment for every affected person already during early disease course. Our work could also pave the way for new treatments that target the specific needs of each T1D subtype, offering hope for better management of the disease in the future.