Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes: Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S.
Year: 2021
Type: article
Abstract: OBJECTIVE: To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes. RESEARCH DESIGN AND METHODS: For prospective cohorts in Finland, Germany, Sweden, and the U.S., 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes have been followed. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years. RESULTS: In the infant-toddler cohort, 1,413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two, or three autoantibodies at seroconversion: 45% (95% CI 40-52), 85% (78-90), and 92% (85-97), respectively. Among those with a single autoantibody, status 2 years after seroconversion predicted diabetes risk: 12% (10-25) if reverting to autoantibody negative, 30% (20-40) if retaining a single autoantibody, and 82% (80-95) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single-autoantibody status. Their 15-year diabetes incidence for higher- versus lower-risk genotypes was 40% (28-50) vs. 12% (5-38). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies, ranging from 20% per year to 6% per year in children developing multipositivity in ≤2 years or >7.4 years, respectively. CONCLUSIONS: The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining a single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.
Source: Diabetes Care
DOI: 10.2337/dc20-1836
Authors: Vibha Anand, Ying Li, Bin Liu, Mohamed Ghalwash, Eileen Koski, Kenney Ng, Jessica L. Dunne, Josefine Jönsson, Christiane Winkler, Mikael Knip, Jorma Toppari, Jorma Ilonen, Michael B. Killian, Brigitte I. Frohnert, Markus Lundgren, Anette-Gabriele Ziegler, William Hagopian, Riitta Veijola, Marian Rewers
Institutions: IBM (United States), IBM Research - Thomas J. Watson Research Center, Ain Shams University, Breakthrough T1D, Lund University, Skåne University Hospital, Helmholtz Munich, Institute of Diabetes Research, Technical University of Munich, University of Helsinki, Helsinki University Hospital, Tampere University Hospital, Folkhälsans Forskningscentrum, University of Turku, Turku University Hospital, University of Colorado Denver, Oulu University Hospital, University of Oulu
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: G1969949363, G288617984, Natural History of Pre-Diabetic Autoimmunity (DAISY), G5320929254, Islet Cell Membrane Antibodies in Diabetes, Natural History of Pre-diabetic Autoimmunity (DAISY), G7546696832, Nutrigenetics & -genomics of Vitamin D and Omega-3 Fatty Acids in Type 1 Diabetes, MULTILPLE AUTOANTIGENS OF PRETYPE I DM, G9000051206, G9000160037, University of Colorado Anschutz Medical Campus DRC, Multiple Autoantigens, Multiple Epitopes of Type 1 Diabetes
OpenAlex ID: W3173682566