title: Metabolic tests to determine risk for type 1 diabetes in clinical trials.
abstract: OBJECTIVE
  Evaluate the reproducibility and relationship of various metabolic tests conducted as part of the Diabetes Prevention Trial-type 1 diabetes.
  
  
  METHODS
  Coefficients of variation, intraclass correlation coefficients, and Pearson correlations between the same metabolic tests performed at different times as well as the different tests were determined.
  
  
  RESULTS
  Fasting samples on the same day had a coefficient of variation of < 10 for C-peptide, 11 for insulin, and 2 for glucose. Testing on separate days approximately doubled the variance. Stimulated insulin values had less variance than fasting values and there was only a moderate correlation between fasting and stimulated values on each test. While highly correlated, C-peptide values from mixed meal tolerance tests are significantly lower than that obtained during oral glucose tolerance tests (OGTTs). Neither peak nor area under the curve C-peptide on the oral glucose tolerance test was different between those with abnormal and normal glucose tolerance. Those with abnormal as compared with normal glucose tolerance had lower 30-min C-peptide and a longer time to peak C-peptide.
  
  
  CONCLUSIONS
  A large, multi-centre trial, with tests performed over a decade-long period, can provide robust data. C-peptide data from oral glucose tolerance tests and mixed meal tolerance tests differ; therefore, the same stimulation test should be used to evaluate changes in beta cell function over time. Worsening glucose tolerance is associated with lower C-peptide at 30 min and a delay in peak secretion on the oral glucose tolerance test. This Diabetes Prevention Trial-type 1 diabetes data can be used in planning parameters for future studies, including evaluation of new algorithms to determine risk of disease.
authors.affiliation: Diabetes Program, Benaroya Research Institute, Seattle, WA 98101, USA. cjgreen@benaroyaresearch.org
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: B
authors.initials: B
authors.lastname: Buckingham
authors.forename: H P
authors.initials: HP
authors.lastname: Chase
authors.forename: J
authors.initials: J
authors.lastname: Krischer
mesh_terms: D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood*; D002986:Clinical Trials as Topic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000378:metabolism*; D005215:Fasting; D005502:Food; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology; D011236:Prediabetic State / Q000378:metabolism; D015203:Reproducibility of Results; D012306:Risk
chemical_list: D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin