The TrialNet natural history study of the development of type 1 diabetes: Objectives, design, and initial results

Jeffrey L. Mahon, Jay M. Sosenko, Lisa Rafkin-Mervis, Heidi Krause-Steinrauf, John M. Lachin, Clinton Thompson, Polly J. Bingley, Ezio Bonifacio, Jerry P. Palmer, George S. Eisenbarth, Joseph Wolfsdorf, Jay S. Skyler

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Objectives: TrialNet's goal to test preventions for type 1 diabetes has created an opportunity to gain new insights into the natural history of pre-type 1 diabetes. The TrialNet Natural History Study (NHS) will assess the predictive value of existing and novel risk markers for type 1 diabetes and will find subjects for prevention trials. Research design and methods: The NHS is a three-phase, prospective cohort study. In phase 1 (screening), pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell antibodies) are measured. Phase 2 (baseline risk assessment) includes oral glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5-yr diabetes risks according to the OGTT and number of confirmed positive antibody tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6months. In phases 2 and 3, samples are collected for future tests of T-lymphocyte function, autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome is diabetes onset. Results: Of 12636 relatives screened between March 2004 and December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of these, 322 were confirmed antibody positive and completed phase 2, of whom 296 subjects were given preliminary 5-yr diabetes risks of <25% (n = 132), ≥25% (n = 36), and ≥50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, ≥25%; 3 or more, ≥50%) and/or an abnormal OGTT (≥50%). Conclusions: The NHS is identifying potential prevention trial subjects and is assembling a large cohort that will provide new natural history information about pre-type 1 diabetes. Follow-up to diabetes will help establish the biological significance and clinical value of novel type 1 diabetes risk markers.

Original languageEnglish (US)
Pages (from-to)97-104
Number of pages8
JournalPediatric Diabetes
Volume10
Issue number2
DOIs
StatePublished - Mar 10 2009

Keywords

  • Natural history
  • Pre-type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism

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