Paving the way for evidence-based population screening for type 1 diabetes.

Abstract

Since the 1980s, we have been gaining knowledge about the pathogenesis of type 1 diabetes and found that the measurement of diabetes-associated autoantibodies against insulin, glutamic acid decarboxylase, insulinoma-associated protein 2, and zinc transporter 8 has a central role in recognition of early stages of the disease in asymptomatic people. In the 1990s, large prospective studies were established in Finland (the Diabetes Prediction and Prevention [DIPP] study 1 Kupila A Muona P Simell T et al. Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort. Diabetologia. 2001; 44: 290-297 Crossref PubMed Scopus (268) Google Scholar ), Germany (the BABYDIAB study 2 Ziegler AG Hummel M Schenker M Bonifacio E Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB study. Diabetes. 1999; 48: 460-468 Crossref PubMed Scopus (536) Google Scholar ), Sweden (Diabetes Prediction in Skåne Study 3 Elding Larsson H A Swedish approach to the prevention of type 1 diabetes. Pediatr Diabetes. 2016; 17: 73-77 Crossref PubMed Scopus (13) Google Scholar ), and the USA (the Diabetes Autoimmunity Study in the Young [DAISY] 4 Rewers M Bugawan TL Norris JM et al. Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia. 1996; 39: 807-812 Crossref PubMed Scopus (349) Google Scholar ) that followed up children with a high genetic risk of developing type 1 diabetes from birth until diagnosis of clinical type 1 diabetes. On the basis of these findings, confirmed positivity for multiple (at least two) autoantibodies predicts almost inevitable progression to clinical type 1 diabetes within 15 years from seroconversion 5 Insel RA Dunne JL Atkinson MA et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015; 38: 1964-1974 Crossref PubMed Scopus (473) Google Scholar and thus allows the diagnosis before clinical symptoms develop. However, the disease's progression shows a high variability and mostly depends on the age at which seroconversion occurs, with prechoolers having a faster decline of residual β-cell function than adolescents. Therefore, to better understand the interaction between genetics and environmental factors in children with a high genetic risk of type 1 diabetes, further large prospective studies, such as TEDDY 6 TEDDY Study GroupThe Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes. 2007; 8: 286-298 Crossref PubMed Scopus (219) Google Scholar or Diabetes Evaluation in Washington (DEW‑IT), 7 Wion E Brantley M Stevens J et al. Population-wide infant screening for HLA-based type 1 diabetes risk via dried blood spots from the public health infrastructure. Ann NY Acad Sci. 2003; 1005: 400-403 Crossref PubMed Scopus (24) Google Scholar were established in the USA in the early 2000s. Although maximum autoantibody conversion occurs between the first and second year of life, approximately 20% of children develop multiple antibodies after 5 years of age. Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort studyScreening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Full-Text PDF