title: Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients.
abstract: OBJECTIVE
  In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D).
  
  
  METHODS
  The design is a registry-based study.
  
  
  METHODS
  Functional tests were performed in a hospital setting.
  
  
  METHODS
  Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years).
  
  
  METHODS
  We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62).
  
  
  RESULTS
  Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min).
  
  
  CONCLUSIONS
  Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.
authors.affiliation: Diabetes Research Center (E.V.B., E.V., I.W., A.V., S.D., P.G., B.K., D.G.P., K.D., F.K.G.), Brussels Free University-VUB, Brussels, Belgium; Department of Clinical Chemistry and Radio-Immunology (E.V.B., I.W., A.V., S.D., K.V., F.K.G.), University Hospital Brussels-UZ Brussel, Brussels, Belgium; Diabetes Clinic (E.V., U.V., B.K., K.D.), University Hospital Brussels-UZ Brussel, Brussels, Belgium; Department of Clinical and Experimental Medicine (P.G.), University of Leuven-KUL and University Hospital Leuven, Leuven, Belgium; Department of Endocrinology (C.D.), Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium; and Department of Endocrinology (J.R.), University of Ghent, Ghent, Belgium.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Balti
authors.forename: Evy
authors.initials: E
authors.lastname: Vandemeulebroucke
authors.forename: Ilse
authors.initials: I
authors.lastname: Weets
authors.forename: Ursule
authors.initials: U
authors.lastname: Van De Velde
authors.forename: Annelien
authors.initials: A
authors.lastname: Van Dalem
authors.forename: Simke
authors.initials: S
authors.lastname: Demeester
authors.forename: Katrijn
authors.initials: K
authors.lastname: Verhaeghen
authors.forename: Pieter
authors.initials: P
authors.lastname: Gillard
authors.forename: Christophe
authors.initials: C
authors.lastname: De Block
authors.forename: Johannes
authors.initials: J
authors.lastname: Ruige
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pipeleers
authors.forename: Katelijn
authors.initials: K
authors.lastname: Decochez
authors.forename: Frans K
authors.initials: FK
authors.lastname: Gorus
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D016241:Child of Impaired Parents; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology; D005260:Female; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D011237:Predictive Value of Tests; D012372:ROC Curve; D035781:Siblings; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007328:Insulin