title: Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study.
abstract: OBJECTIVE
  Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study.
  
  
  METHODS
  Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models.
  
  
  RESULTS
  Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month).
  
  
  CONCLUSIONS
  SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 East 17th Ave, Aurora, CO 80045, USA. Dana.Dabelea@ucdenver.edu
authors.forename: D
authors.initials: D
authors.lastname: Dabelea
authors.forename: E J
authors.initials: EJ
authors.lastname: Mayer-Davis
authors.forename: J S
authors.initials: JS
authors.lastname: Andrews
authors.forename: L M
authors.initials: LM
authors.lastname: Dolan
authors.forename: C
authors.initials: C
authors.lastname: Pihoker
authors.forename: R F
authors.initials: RF
authors.lastname: Hamman
authors.forename: C
authors.initials: C
authors.lastname: Greenbaum
authors.forename: S
authors.initials: S
authors.lastname: Marcovina
authors.forename: W
authors.initials: W
authors.lastname: Fujimoto
authors.forename: B
authors.initials: B
authors.lastname: Linder
authors.forename: G
authors.initials: G
authors.lastname: Imperatore
authors.forename: R
authors.initials: R
authors.lastname: D'Agostino
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000378:metabolism*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D018450:Disease Progression; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D011237:Predictive Value of Tests; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D002096:C-Peptide; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human