title: Two-step islet autoantibody screening for risk assessment of type 1 diabetes in relatives.
abstract: OBJECTIVE
  To examine the performance of islet cell antibodies (ICAs) and antibodies to glutamate decarboxylase (GADA), IA-2 (IA-2 antibody [IA-2A]), and insulin (insulin autoantibody [IAA]), alone and in combination, in assessing type 1 diabetes risk within type 1 diabetic families to identify a practical and effective screening strategy for predicting type 1 diabetes in relatives.
  
  
  METHODS
  ICA, GADA, IA-2A, and IAA were determined in 806 first-degree relatives participating in a prospective type 1 diabetes family study (median follow-up 6.17 years, range 0.6-8.3). The conferred risk of developing type 1 diabetes within 6 years was evaluated by Kaplan-Meier for each antibody marker, used alone or in combination.
  
  
  RESULTS
  ICAs were detected in 3%, GADA in 5.1%, IA-2A in 2.5%, and IAA in 3.7% of relatives; > or =1 antibody markers were detected in 10.7% of relatives and > or =2 were detected in 1.9% of relatives. The risk of type 1 diabetes at 6 years was 1.5% in relatives with only 1 marker and 24.8% in relatives with > or =2 markers. As a practical and effective strategy for type 1 diabetes risk assessment in relatives, this study indicates a first-step screening based on GADA and IA-2A measurement--which identified 6.5% of relatives, including all who developed the disease, with a 6-year type 1 diabetes risk of 9.0%--followed by a second step based on ICA and IAA measurement in relatives with either GADA or IA-2A, which identified a total of 1.9% of all relatives as having > or =2 markers, and a 6-year risk of 24.8%, including 6 of 7 who developed type 1 diabetes.
  
  
  CONCLUSIONS
  A two-step antibody screening, based first on GADA and IA-2A and then on ICA and IAA measurements in identified individuals, is likely to be a practical, sensitive, and effective strategy for predicting type 1 diabetes in first-degree relatives.
authors.affiliation: Department of Internal Medicine, Istituto Scientifico Ospedale San Raffaele, University of Milan, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Pastore
authors.forename: E
authors.initials: E
authors.lastname: Bazzigaluppi
authors.forename: R
authors.initials: R
authors.lastname: Bonfanti
authors.forename: N
authors.initials: N
authors.lastname: Dozio
authors.forename: A
authors.initials: A
authors.lastname: Sergi
authors.forename: A
authors.initials: A
authors.lastname: Balini
authors.forename: C
authors.initials: C
authors.lastname: Belloni
authors.forename: F
authors.initials: F
authors.lastname: Meschi
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
authors.forename: E
authors.initials: E
authors.lastname: Bosi
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D005190:Family; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D015995:Prevalence; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C096322:ICA512 autoantibody; D007328:Insulin; C024211:islet cell antibody; D005968:Glutamate Decarboxylase