title: Autoantibody-defined risk for Type 1 diabetes mellitus in a general population of schoolchildren: results of the Karlsburg Type 1 Diabetes Risk Study after 18 years.
abstract: OBJECTIVE
  To investigate the occurrence of diabetes-associated autoantibodies and cumulative Type 1 diabetes risk over 18 years in a general population of schoolchildren.
  
  
  METHODS
  In the Karlsburg Type 1 Diabetes Risk Study, 11 986 schoolchildren from north-eastern Germany without a family history of diabetes were screened for glutamic acid decarboxylase antibodies, insulinoma-associated antigen-2 antibodies and insulin autoantibodies by radioligand binding assay. Those children found to be autoantibody-positive were invited to follow-up examinations and HLA-DQB1 genotyping, and were followed for progression to Type 1 diabetes.
  
  
  RESULTS
  At first follow-up, 119 children had single and 36 children had multiple autoantibodies. Of the multiple autoantibody-positive children, 33 had at least one diabetes-associated HLA-DQB1 allele (*02 and/or *0302). A total of 26 children progressed to Type 1 diabetes, of whom 22 had multiple autoantibodies. The male-to-female ratio of those who progressed to Type 1 diabetes was 1.6. The positive predictive value of multiple autoantibodies was 61.1% compared with only 23.7% for diabetes-associated HLA-DQB1 genotypes among all those who were autoantibody-positive. The cumulative risk was 59.7% after 10 years and 75.1% after 18 years for children with multiple autoantibodies compared with 1.2 and 22.6%, respectively, for children with single autoantibodies (P<0.001). Among the three examined autoantibodies, insulinoma-associated antigen-2 antibodies conferred the highest risk.
  
  
  CONCLUSIONS
  The diabetes risk in schoolchildren with multiple autoantibodies was similar to the risk reported in other studies for genetically preselected probands; thus, a combined autoantibody-based screening could effectively identify at-risk individuals from the general population for future intervention trials.
authors.affiliation: Department of Pediatrics, Greifswald University Medical Centre, Greifswald, Germany.
authors.forename: A-M
authors.initials: AM
authors.lastname: Till
authors.affiliation: Institute of Pathophysiology, Research Group of Predictive Diagnostics, Greifswald University Medical Centre, Karlsburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kenk
authors.affiliation: Centre of Diabetes and Metabolic Disorders, Karlsburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Rjasanowski
authors.affiliation: Department of Quality Management, University Medical Centre, University of Duesseldorf, Duesseldorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wassmuth
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Research Group of Predictive Diagnostics, University Medical Centre Greifswald, Karlsburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Walschus
authors.affiliation: Centre of Diabetes and Metabolic Disorders, Karlsburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kerner
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Research Group of Predictive Diagnostics, University Medical Centre Greifswald, Karlsburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schlosser
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D005968:Glutamate Decarboxylase / Q000276:immunology*; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D007330:Insulin Antibodies / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012097:Repressor Proteins / Q000276:immunology*; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D017678:Sex Distribution; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007330:Insulin Antibodies; D012097:Repressor Proteins; C087342:INSM1 protein, human; D005968:Glutamate Decarboxylase