title: A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history.
abstract: OBJECTIVE
  We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals.
  
  
  METHODS
  Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed from 2-h oral glucose tolerance tests (OGTTs) using the log fasting C-peptide, 60-min C-peptide, and 60-min glucose. OGTTs with Index60 ≥2.00 and 2-h glucose <200 mg/dL (Ind60+Only) were compared with Index60 <2.00 and 2-h glucose ≥200 mg/dL (2hglu+Only) OGTTs as criteria for T1D. Individuals were assessed for C-peptide loss from the first Ind60+Only OGTT to diagnosis.
  
  
  RESULTS
  Areas under receiver operating characteristic curves were significantly higher for Index60 than for the 2-h glucose (P < 0.001 for both DPT-1 and the TNNHS). As a diagnostic criterion, sensitivity was higher for Ind60+Only than for 2hglu+Only (0.44 vs. 0.15 in DPT-1; 0.26 vs. 0.17 in the TNNHS) OGTTs. Specificity was somewhat higher for 2hglu+Only OGTTs in DPT-1 (0.97 vs. 0.91) but equivalent in the TNNHS (0.98 for both). Positive and negative predictive values were higher for Ind60+Only OGTTs in both studies. Postchallenge C-peptide levels declined significantly at each OGTT time point from the first Ind60+Only OGTT to the time of standard diagnosis (range -22 to -34% in DPT-1 and -14 to -27% in the TNNHS). C-peptide and glucose patterns differed markedly between Ind60+Only and 2hglu+Only OGTTs.
  
  
  CONCLUSIONS
  An approach based on prediction and natural history appears to have utility for diagnosing T1D.
authors.affiliation: Division of Endocrinology, University of Miami, Miami, FL jsosenko@med.miami.edu.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Sosenko
authors.affiliation: Division of Endocrinology, University of Miami, Miami, FL.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.affiliation: Section of Pediatric Endocrinology/Diabetology, Indiana University, Indianapolis, IN.
authors.forename: Linda A
authors.initials: LA
authors.lastname: DiMeglio
authors.affiliation: Division of Epidemiology and Biostatistics, University of Western Michigan School of Medicine, Kalamazoo, MI.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Beam
authors.affiliation: Division of Informatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.affiliation: Division of Informatics and Biostatistics, University of South Florida, Tampa, FL.
authors.forename: David
authors.initials: D
authors.lastname: Boulware
authors.affiliation: Division of Endocrinology, University of Miami, Miami, FL.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Rafkin
authors.affiliation: Division of Endocrinology, University of Miami, Miami, FL.
authors.forename: Della
authors.initials: D
authors.lastname: Matheson
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.affiliation: Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mahon
authors.affiliation: VA Puget Sound Health Care System, Division of Endocrinology, Metabolism, and Nutrition, University of Washington, Seattle, WA.
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000378:metabolism*; D001681:Biological Assay / Q000379:methods; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000378:metabolism; D042241:Early Diagnosis; D004812:Epidemiologic Methods; D005215:Fasting / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide