title: Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective.
abstract: BACKGROUND
  Type 1 diabetes (T1D) TrialNet is a National Institutes of Health-sponsored clinical trial network aimed at altering the disease course of T1D. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic and immunologic characteristics of individuals with recent-onset T1D, to identify cohorts of interest and to aid in planning of future studies.
  
  
  METHODS
  Eight hundred eighty-three individuals with recent-onset T1D involved in five TrialNet studies were categorized by age as follows: ≥18 years, 12-17 years, 8-12 years and <8 years. Data were compared with healthy age-matched subjects in the National Health and Nutrition Examination Survey.
  
  
  RESULTS
  Only 2.0% of the individuals overall were excluded from trial participation because of insufficient C-peptide values (<0.2 pmol/mL). A disproportionate number of these subjects were <8 years old. Leukopenia was present in 21.2% of individuals and lymphopenia in 11.6%; these frequencies were markedly higher than age-matched healthy National Health and Nutrition Examination Survey population. Of the cohort, 24.5% were overweight or obese. Neither high-risk human leukocyte antigen type DR3 nor DR4 was present in 31% of adults and 21% of children.
  
  
  CONCLUSIONS
  The ability of recent-onset T1D patients to meet key entry criteria for TrialNet studies, including C-peptide >0.2 pmol/mL, varies by age. Lower C-peptide level requirements for younger participants and other aspects of heterogeneity of recent-onset T1D patients, such as white blood cell count abnormalities and body mass index should be considered in the design of future clinical studies.
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Bollyky
authors.affiliation: Pediatric Epidemiology Center, University of South Florida, Tampa, FL, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Division of Systems Medicine, Department of Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.affiliation: Department of Pediatrics, Division of Endocrinology, Stanford University, Stanford, CA, USA.
authors.forename: Darrell M
authors.initials: DM
authors.lastname: Wilson
authors.affiliation: Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Beam
authors.affiliation: Benaroya Research Institute, Seattle, WA, USA.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001323:Autoantibodies / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007558:Italy; D007970:Leukopenia / Q000150:complications*; D008231:Lymphopenia / Q000150:complications*; D008875:Middle Aged; D009656:North America; D009765:Obesity / Q000150:complications*; D050177:Overweight / Q000150:complications*; D063766:Pediatric Obesity / Q000150:complications*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D002096:C-Peptide
keywords: C-peptide; type 1 diabetes TrialNet; type 1 diabetes clinical trials