title: Reference intervals for C-peptide and insulin derived from a general adult Danish population.
abstract: BACKGROUND
  Despite international efforts to standardize C-peptide and insulin calibrators and immunoassays, platform dependent differences still exist, and platform specific reference intervals are hence needed for correct interpretation. We therefore wanted to establish traceable reference intervals for C-peptide and insulin.
  
  
  METHODS
  In 623 consecutively recruited participants, insulin and C-peptide were measured using the Cobas e411 (Roche Diagnostics, Switzerland). Participants with diabetes were excluded (fasting Glucose ≥7.0mmol/L or HbA1c≥6.5%/≥48mmol/L) and reference intervals were calculated with and without the inclusion of persons who were prediabetic, according to two definitions (The World Health Organization (WHO) and American Diabetes Association (ADA)). To ensure the correctness of calibration, the control pools were analyzed by a reference laboratory. The reference intervals were calculated according to the IFCC guidelines, using the RefVal software (Solberg, Oslo, Norway).
  
  
  RESULTS
  Comparison of our results with those from the reference laboratory revealed equivalence for C-peptide results whereas the insulin determined on the Cobas e411 assay were 15-20% higher. The difference is attributed to an incorrect conversion factor for converting from activity to metric units. The Cobas e411 assay uses the factor 6.945 for converting from U/mL to pmol/L. This is in disagreement with the biological activity of insulin which is 166.8×106IU/mol or 6.00nmol/IU.
  
  
  CONCLUSIONS
  We successfully established reference intervals for C-peptide and insulin for non-diabetic and prediabetic participants. The reference intervals for fasting C-peptide and fasting insulin are ready for implementation. A recertification of the insulin standards is needed.
authors.affiliation: Department of Clinical Biochemistry, Slagelse Hospital, Slagelse, Denmark. Electronic address: frk.pia.larsen@gmail.com.
authors.forename: Pia Bükmann
authors.initials: PB
authors.lastname: Larsen
authors.affiliation: Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Section of Metabolic Genetics, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Department of Clinical Biochemistry, Nordsjællands Hospital, Hillerød, Denmark; Steno Diabetes Center, Copenhagen, Denmark. Electronic address: Lennart.jan.friis-hansen@regionh.dk.
authors.forename: Lennart
authors.initials: L
authors.lastname: Friis-Hansen
mesh_terms: D000328:Adult; D000368:Aged; D002096:C-Peptide / Q000097:blood*; D003718:Denmark; D005215:Fasting / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay / Q000379:methods / Q000592:standards; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000097:blood*
chemical_list: D002096:C-Peptide; D007328:Insulin
keywords: C-Peptide; Diabetes mellitus; Insulin; Prediabetic state; Radioimmunoassay; Reference values