title: Age-dependent decline of β-cell function in type 1 diabetes after diagnosis: a multi-centre longitudinal study.
abstract: OBJECTIVE
  C-peptide secretion is currently the only available clinical biomarker to measure residual β-cell function in type 1 diabetes. However, the natural history of C-peptide decline after diagnosis can vary considerably dependent upon several variables. We investigated the shape of C-peptide decline over time from type 1 diabetes onset in relation to age at diagnosis, haemoglobin A1c (HbA1c) levels and insulin dose.
  
  
  METHODS
  We analysed data from 3929 type 1 diabetes patients recruited from seven European centres representing all age groups at disease onset (childhood, adolescence and adulthood). The influence of the age at onset on β-cell function was investigated in a longitudinal analysis at diagnosis and up to 5-years follow-up.
  
  
  RESULTS
  Fasting C-peptide (FCP) data at diagnosis were available in 3668 patients stratified according to age at diagnosis in four groups (<5 years, n = 344; >5 years < 10 years, n = 668; >10 years < 18 years, n = 991; >18 years, n = 1655). FCP levels were positively correlated with age (p < 0.001); the subsequent decline in FCP over time was log-linear with a greater decline rate in younger age groups (p < 0.0001).
  
  
  CONCLUSIONS
  This study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of β-cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.
authors.affiliation: Department MRC Epidemiology Unit, Cambridge Institute of Public Health, Cambridge, UK.
authors.forename: A
authors.initials: A
authors.lastname: Barker
authors.forename: A
authors.initials: A
authors.lastname: Lauria
authors.forename: N
authors.initials: N
authors.lastname: Schloot
authors.forename: N
authors.initials: N
authors.lastname: Hosszufalusi
authors.forename: J
authors.initials: J
authors.lastname: Ludvigsson
authors.forename: C
authors.initials: C
authors.lastname: Mathieu
authors.forename: D
authors.initials: D
authors.lastname: Mauricio
authors.forename: M
authors.initials: M
authors.lastname: Nordwall
authors.forename: B
authors.initials: B
authors.lastname: Van der Schueren
authors.forename: T
authors.initials: T
authors.lastname: Mandrup-Poulsen
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
authors.forename: I
authors.initials: I
authors.lastname: Weets
authors.forename: F K
authors.initials: FK
authors.lastname: Gorus
authors.forename: N
authors.initials: N
authors.lastname: Wareham
authors.forename: R D
authors.initials: RD
authors.lastname: Leslie
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000375:Aging / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005060:Europe; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007330:Insulin Antibodies / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D007330:Insulin Antibodies
keywords: clinical trial; type 1 diabetes; β cell