title: Disease progression among 446 children with newly diagnosed type 1 diabetes located in Scandinavia, Europe, and North America during the last 27 yr.
abstract: OBJECTIVE
  To clarify whether the rate of decline in stimulated C-peptide (SCP) from 2 to 15 months after diagnosis has changed over an interval of 27 yr.
  
  
  METHODS
  The rate of decline in SCP levels at 1, 2, 3, 6, 9, 12, and 15 months after diagnosis was compared in four paediatric cohorts from Scandinavian and European countries including 446 children with new onset type 1 diabetes (T1D, 1982-2004). Findings were evaluated against 78 children (2004-2009) from the TrialNet studies.
  
  
  RESULTS
  The mean rate of decline [%/month (±SEM)] in SCP for a 10-yr-old child was 7.7%/month (±1.5) in the 1982-1985 Cohort, 6.3%/month (±1.7) in the 1995-1998 Cohort, 7.8%/month (±0.7) in the 1999-2000 Cohort, and 10.7%/month (±0.9) in the latest 2004-2005 Cohort (p = 0.05). Including the TrialNet Cohort with a rate of decline in SCP of 10.0%/month (±0.9) the differences between the cohorts are still significant (p = 0.039). The rate of decline in SCP was negatively associated with age (p < 0.0001), insulin antibodies (IA) (p = 0.003), and glutamic acid decarboxylase-65 (GAD65A) (p = 0.03) initially with no statistically significant effect of body mass index (BMI) Z-score at 3 months. Also, at 3 months the time around partial remission, the effect of age on SCP was significantly greater in children ≤5 yr compared with older children (p ≤ 0.0001).
  
  
  CONCLUSIONS
  During the past 27 yr, initial C-peptide as well as the rate of C-peptide decline seem to have increased. The rate of decline was affected significantly by age, GAD65A, and IA, but not BMI Z-score or initial C-peptide.
authors.affiliation: Department of Pediatrics, Herlev Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Herlev, Denmark.
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Max Andersen
authors.forename: Lotte B
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Jannet
authors.initials: J
authors.lastname: Svensson
authors.forename: Sven
authors.initials: S
authors.lastname: Pörksen
authors.forename: Philip
authors.initials: P
authors.lastname: Hougaard
authors.forename: Craig
authors.initials: C
authors.lastname: Beam
authors.forename: Carla
authors.initials: C
authors.lastname: Greenbaum
authors.forename: Dorothy
authors.initials: D
authors.lastname: Becker
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Petersen
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Henrik B
authors.initials: HB
authors.lastname: Mortensen
mesh_terms: D015992:Body Mass Index; D002096:C-Peptide / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D005060:Europe; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000378:metabolism; D008297:Male; D009656:North America; D012537:Scandinavian and Nordic Countries; D044465:White People
chemical_list: D002096:C-Peptide; D007330:Insulin Antibodies; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: C-peptide; children; diabetes mellitus; rate of decline; type 1