Objective
In our study, we want to determine the frequency of early-stage T1D (multiple positive islet autoantibodies) and the frequency of single positive islet autoantibodies in adults.
In individuals with early-stage T1D, we want to assess how often an already advanced early stage (stage 2) is present.
We want to find out what the 5-year risk of developing T1D is in adults with islet autoantibodies.
We want to investigate how islet autoantibodies develop from childhood and adolescence into adulthood and which factors play a role in this process.
We also want to investigate whether islet autoantibodies continue to develop or disappear in adulthood.
We want to identify profiles of islet autoantibodies and other factors that can help make the correct diagnosis of T1D in adults.
Background Rationale
The frequency of type 1 diabetes (T1D) is increasing worldwide, and more than half of clinical manifestations occur in adults. It is currently unclear to what extent the risk factors for developing T1D are identical in children and adults. The detection of islet autoantibodies in the blood makes it possible to identify and assess the risk of T1D long before clinical symptoms appear. Multiple positive islet autoantibodies indicate early-stage T1D. To date, little information is available on the frequency and diagnostic value of islet autoantibodies in the general adult population.
In our study, we aim to detect islet autoantibodies in adults and investigate their association with the development of clinical diabetes. To this end, we have access to data and blood samples from more than 75,000 participants in the NAKO study. In addition, we can investigate which profiles of islet autoantibodies and other factors are associated with progression to clinical diabetes within 5 years. In particular, the relevance of single positive islet autoantibodies detected in adults can be determined and assessed in terms of progression to early-stage T1D and clinical T1D. We expect that new diagnostic profiles can be identified and will enable improved prediction of diabetes risk in adults with both single and multiple positive islet autoantibodies. In addition, we have access to data from the Babydiab/Babydiet study, in which more than 2,000 participants were examined from birth through childhood and adolescence to adulthood. This allows us to study the development of islet autoantibodies from childhood and adolescence to adulthood. Furthermore, a broader selection of tests for islet autoantibodies in combination with other factors, such as genetic testing, could help improve diagnostic accuracy in adults, prevent misdiagnosis of T1D in adulthood, and distinguish T1D from T2D.
Description of Project
The majority of new cases of type 1 diabetes (T1D) occur in adults. It is currently unclear to what extent the risk factors for developing T1D are identical in children and adults. The detection of islet autoantibodies in the blood makes it possible to identify and assess the risk of T1D long before clinical symptoms appear. Multiple positive islet autoantibodies indicate early-stage T1D. To date, little information is available on the frequency and diagnostic value of islet autoantibodies in the general adult population. We want to use a very large study cohort to determine which autoantibodies and criteria are suitable for assessing the early stages and development of T1D in adults.
The German National Cohort (NAKO; www.nako.de) is a population-based cohort study that aims to investigate the causes of widespread diseases, identify risk factors, and improve early detection and prevention of diseases. More than 200,000 adults were recruited and examined in 18 study centers in Germany. The cohort has a balanced age and gender distribution. The participants live in urban and rural regions of Germany. People with a migration background are well represented, accounting for 16% of the cohort. The Babydiab/Babydiet study cohort comprises 2,441 first-degree relatives of individuals with T1D from Germany who were regularly examined from birth to over 30 years of age for the development of islet autoantibodies and T1D.
We will examine blood samples from more than 75,000 participants in the NAKO study aged between 19 and 52 for islet autoantibodies and determine the frequency of early-stage T1D (multiple positive islet autoantibodies) and of single positive islet autoantibodies. In samples from the Babydiab/Babydiet study, we will investigate how islet autoantibodies develop from childhood through adolescence to adulthood and which factors are involved. We will determine the risk that adults with multiple, single, or no islet autoantibodies have of developing T1D within 5 years, and how this risk can be assessed even more accurately. We can assess the effect of genetic risk factors in combination with metabolic factors and islet autoantibodies. By researching specific profiles of islet autoantibodies and additional factors, we aim to improve the clinical diagnosis of T1D in adults so that delays in receiving the right treatment can be avoided.
The planned study could provide important insights into the frequency and significance of islet autoantibodies in relation to the development of T1D in adults, thereby offering opportunities for earlier diagnosis and treatment. Based on our experience in studies with children, we know that early detection of islet autoantibodies can minimize the risk of a medical emergency (ketoacidosis) when T1D develops. We believe that similar benefits can be transferred to adults and that the results of our study could serve as a guide for future screening programs.
Anticipated Outcome
We will define the prevalence of early-stage T1D and single positive islet autoantibodies in the adult population in Germany aged between 19 and 52 years, and estimate the prevalence of advanced early-stage T1D (stage 2). This will serve as an important reference for other countries and future screening studies in adults and for immunotherapy in early-stage T1D.
We will define the risk of adults with multiple, single, or no islet autoantibodies developing T1D within 5 years. This will in turn be an important reference for the follow-up care of individuals with early-stage T1D and for new treatments.
We will show how islet autoantibodies develop from birth to adulthood and which factors play a role in this process.
We will contribute to improving the clinical diagnosis of T1D in adults by evaluating a broad spectrum of different islet autoantibodies and additional factors.
Relevance to T1D
The planned study could provide important insights into the frequency and significance of islet autoantibodies in relation to the development of T1D in adults, thereby offering opportunities for earlier diagnosis and treatment. Based on our experience in studies with children, we know that early detection of islet autoantibodies can minimize the risk of a medical emergency (ketoacidosis) when T1D develops. We believe that similar benefits can be transferred to adults and that the results of our study could serve as a guide for future screening programs.