title: Persistence of prolonged C-peptide production in type 1 diabetes as measured with an ultrasensitive C-peptide assay.
abstract: OBJECTIVE
  To examine persistence of C-peptide production by ultrasensitive assay years after onset of type 1 diabetes and factors associated with preserving β-cell function.
  
  
  METHODS
  Serum C-peptide levels, a marker of insulin production and surviving β-cells, were measured in human subjects (n = 182) by ultrasensitive assay, as was β-cell functioning. Twenty-two times more sensitive than standard assays, this assay's lower detection limit is 1.5 pmol/L. Disease duration, age at onset, age, sex, and autoantibody titers were analyzed by regression analysis to determine their relationship to C-peptide production. Another group of four patients was serially studied for up to 20 weeks to examine C-peptide levels and functioning.
  
  
  RESULTS
  The ultrasensitive assay detected C-peptide in 10% of individuals 31-40 years after disease onset and with percentages higher at shorter duration. Levels as low as 2.8 ± 1.1 pmol/L responded to hyperglycemia with increased C-peptide production, indicating residual β-cell functioning. Several other analyses showed that β-cells, whose C-peptide production was formerly undetectable, were capable of functioning. Multivariate analysis found disease duration (β = -2.721; P = 0.005) and level of zinc transporter 8 autoantibodies (β = 0.127; P = 0.015) significantly associated with C-peptide production. Unexpectedly, onset at >40 years of age was associated with low C-peptide production, despite short disease duration.
  
  
  CONCLUSIONS
  The ultrasensitive assay revealed that C-peptide production persists for decades after disease onset and remains functionally responsive. These findings suggest that patients with advanced disease, whose β-cell function was thought to have long ceased, may benefit from interventions to preserve β-cell function or to prevent complications.
authors.affiliation: Immunobiology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.forename: Nicholas Fraser
authors.initials: NF
authors.lastname: Lovejoy
authors.forename: Denise L
authors.initials: DL
authors.lastname: Faustman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay / Q000379:methods*; D002096:C-Peptide / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D002096:C-Peptide