SummaryBackground/rationale: More than half of the clinical manifestations of type 1 diabetes (T1D) occur in adults. It is currently unclear to what extent the risk factors for the development of T1D are the same in children and adults. The detection of islet autoantibodies in the blood allows for risk stratification long before the onset of clinical symptoms, and the confirmed presence of multiple islet autoantibodies is diagnostic of presymptomatic early-stage T1D. While significant progress has been made in detecting presymptomatic T1D in children, there is limited data on the prevalence and diagnostic value of islet autoantibodies in the adult population. We want to determine, in a large study cohort, which autoantibodies and criteria are suitable for assessing the early stages and development of T1D in adults. Study cohorts: The German National Cohort (NAKO) is a population-based prospective 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 data collected includes height, weight, BMI, HbA1c, and random blood sugar levels, which are recorded for each participant at the start of the study and after 5 years. Participants were genotyped using the Illumina Infinium Global Screening Array-48 v4.0, enabling the determination of the HLA-DR-DQ genotype and genetic risk scores for T1D and T2D. 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. Objectives: The proposed study aims to determine: 1) the prevalence of early-stage T1D and single islet autoantibodypositivity in adults in the NAKO study; 2) the frequency of stage 1 and stage 2 T1D in adults with early-stage T1D; 3) the 5-year risk of progressing from islet autoantibody-positivity to clinical T1D; 4) the evolution of islet autoantibody profiles from birth to adulthood; 5) the temporal dynamics of islet autoantibody profiles in adults. Research plan: We will test for islet autoantibodies in the baseline serum samples of all 76,387 participants in the NAKO study aged between 19 and 52 who took part in the 5-year NAKO follow-up examination. For participants with confirmed positive islet autoantibody findings at baseline (multiple or single positive autoantibodies), the samples taken during the 5-year follow-up study will also be tested for islet autoantibodies. The follow-up data on new-onset diabetes will be used to determine the 5-year risk of developing clinical diabetes depending on the islet autoantibody profile at baseline. Available metadata, including HbA1c and genetics, will be examined for associations with islet autoantibody profiles and for stratification of the 5-year progression rate. In samples from the Babydiab/Babydiet study, we will investigate how islet autoantibodies develop from birth to adulthood and determine progression profiles. We will examine the rate of reversion (loss of autoantibodies), stability (no change), and progression (new autoantibodies) in adulthood and supplement these analyses with extended profiles of islet autoantibodies in adults diagnosed with T1D. 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. Project duration: 3 years Added value: 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.

Keywords Islet-autoantibodies Type-1-Diabetes

InstitutionsHelmholtz Munich, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Institut für Epidemiologie