Heterogeneity in recent-onset type 1 diabetes - a clinical trial perspective

Diabetes Metab Res Rev. 2015 Sep;31(6):588-94. doi: 10.1002/dmrr.2643. Epub 2015 Apr 23.

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.

Keywords: C-peptide; type 1 diabetes TrialNet; type 1 diabetes clinical trials.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Autoantibodies / analysis
  • Biomarkers / blood
  • Body Mass Index
  • C-Peptide / blood
  • Child
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Humans
  • Italy
  • Leukopenia / complications*
  • Lymphopenia / complications*
  • Middle Aged
  • North America
  • Obesity / complications*
  • Overweight / complications*
  • Pediatric Obesity / complications*
  • Young Adult

Substances

  • Autoantibodies
  • Biomarkers
  • C-Peptide

Grants and funding