title: Prediction of type 1 diabetes in Sardinian schoolchildren using islet cell autoantibodies: 10-year follow-up of the Sardinian schoolchildren type 1 diabetes prediction study.
abstract: OBJECTIVE
  Stable genetic background makes individuals from the Mediterranean island of Sardinia ideal to define the predictive power of islet-related autoantibodies (IRAs): glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase-like antibodies (IA-2A), islet cell antibodies (ICA) to identify T1DM progressors. The aims of the present study were: (1) determination of IRAs reference limits in healthy non-diabetic Sardinian schoolchildren (SSc). (2) Predictive power evaluation of IRAs as single or combined determination to identify islet to identify T1DM progressors.
  
  
  METHODS
  Between 1986 and 1994, 8448 SSc were tested for IRAs. All were followed up for 10 years. The predictive power of single or combination of IRAs was determined as hazard ratio (HR), sensitivity, specificity, area under the ROC curve, negative and positive predictive value (NPV, PPV).
  
  
  RESULTS
  All 43 progressors to T1DM, but three showed at least one autoantibody positivity. HR for any single-autoantibody positivity was 55.3 times greater when compared to SSc negative for all IRAs. Any single autoantibody performed at least 64.9 % sensitivity with PPV always lower than 16 %. The best performing combination was ICA, plus IA-2A (showing 52.6 % sensitivity, 99.8 % specificity, 0.76 area under the ROC curve, 51.3 % PPV and 99.8 % NPV.
  
  
  CONCLUSIONS
  Determination of IRAs reference limits in healthy SSc by standard statistical methods is crucial to establish the power of IRAs as progression markers to T1DM. Our data offer a solid rationale for future testing of ICA and IA-2A as routine laboratory markers to identify individuals at high risk of T1DM in the general population.
authors.affiliation: Department of Medical Sciences "Mario Aresu", University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Velluzzi
authors.affiliation: Department of Medical Sciences "Mario Aresu", University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Secci
authors.affiliation: Unit of Nephrology, Dialysis, Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sepe
authors.affiliation: Service of Biometry and Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.affiliation: Department of Immunology, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
authors.forename: Marion
authors.initials: M
authors.lastname: Shattock
authors.affiliation: School of Biomedical and Health Science, King's College, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Foxon
authors.affiliation: Diabetes Unit, Brotzu Hospital, Cagliari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Songini
authors.affiliation: Department of Medical Sciences "Mario Aresu", University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Mariotti
authors.affiliation: Scientific Directorate, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Locatelli
authors.affiliation: Scientific Directorate, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Bottazzo
authors.affiliation: Department of Medical Sciences "Mario Aresu", University of Cagliari, AOU, SS 554, Monserrato, Cagliari, Italy. alovise@medicina.unica.i.
authors.forename: Andrea
authors.initials: A
authors.lastname: Loviselli
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D012574:Schools / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase
keywords: Anti-insula autoantibodies; Epidemiology of T1DM; Prediction of T1DM