Home >> Pediatric Diabetes, Volume 10, Number 2

The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results

Authors: Mahon, Jeffrey L; Sosenko, Jay M1; Rafkin-Mervis, Lisa1; Krause-Steinrauf, Heidi2; Lachin, John M2; Thompson, Clinton2; Bingley, Polly J3; Bonifacio, Ezio4; Palmer, Jerry P5; Eisenbarth, George S6; Wolfsdorf, Joseph7; Skyler, Jay S1

Source: Pediatric Diabetes, Volume 10, Number 2, March 2009 , pp. 97-104(8)

Publisher: Wiley-Blackwell

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Abstract:

Mahon JL, Sosenko JM, Rafkin-Mervis L, Krause-Steinrauf H, Lachin JM, Thompson C, Bingley PJ, Bonifacio E, Palmer JP, Eisenbarth GS, Wolfsdorf J, Skyler JS, for the TrialNet Natural History Committee and Type 1 Diabetes TrialNet Study Group. The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results.

Pediatric Diabetes 2009: 10: 97-104. 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 6 months. 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 12 636 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.

Keywords: pre-type 1 diabetes; natural history

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1399-5448.2008.00464.x

Affiliations: 1: Division of Endocrinology, University of Miami, Miami, FL, USA 2: The Biostatistics Center, George Washington University, Washington, DC, USA 3: Division of Endocrinology and Metabolism, University of Bristol, Bristol, UK 4: Center for Regenerative Therapies, Dresden University of Technology, Dresden, Germany 5: Department of Medicine, University of Washington, Seattle, WA, USA 6: Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO, USA 7: Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA

Publication date: 2009-03-01

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