title: The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells.
abstract: OBJECTIVE
  Classically, type 1 diabetes is thought to proceed to absolute insulin deficiency. Recently developed ultrasensitive assays capable of detecting C-peptide under 5 pmol/l now allow very low levels of C-peptide to be detected in patients with long-standing type 1 diabetes. It is not known whether this low-level endogenous insulin secretion responds to physiological stimuli. We aimed to assess how commonly low-level detectable C-peptide occurs in long-duration type 1 diabetes and whether it responds to a meal stimulus.
  
  
  METHODS
  We performed a mixed-meal tolerance test in 74 volunteers with long-duration (>5 years) type 1 diabetes, i.e. with age at diagnosis 16 (9-23) years (median [interquartile range]) and diabetes duration of 30 (19-41) years. We assessed fasting and stimulated serum C-peptide levels using an electrochemiluminescence assay (detection limit 3.3 pmol/l), and also the urinary C-peptide:creatinine ratio (UCPCR).
  
  
  RESULTS
  Post-stimulation serum C-peptide was detectable at very low levels (>3.3 pmol/l) in 54 of 74 (73%) patients. In all patients with detectable serum C-peptide, C-peptide either increased (n = 43, 80%) or stayed the same (n = 11) in response to a meal, with no indication of levels falling (p < 0.0001). With increasing disease duration, absolute C-peptide levels fell although the numbers with detectable C-peptide remained high (68%, i.e. 25 of 37 patients with >30 years duration). Similar results were obtained for UCPCR.
  
  
  CONCLUSIONS
  Most patients with long-duration type 1 diabetes continue to secrete very low levels of endogenous insulin, which increase after meals. This is consistent with the presence of a small number of still functional beta cells and implies that beta cells are either escaping immune attack or undergoing regeneration.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Oram
authors.forename: Angus G
authors.initials: AG
authors.lastname: Jones
authors.forename: Rachel E J
authors.initials: RE
authors.lastname: Besser
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Knight
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Brown
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McDonald
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D055815:Young Adult
chemical_list: D002096:C-Peptide; D007328:Insulin