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), > or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =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.
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), > or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =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.
Authors: Laura M Jacobsen; Laura Bocchino; Carmella Evans-Molina; Linda DiMeglio; Robin Goland; Darrell M Wilson; Mark A Atkinson; Tandy Aye; William E Russell; John M Wentworth; David Boulware; Susan Geyer; Jay M Sosenko Journal: Diabetologia Date: 2019-11-25 Impact factor: 10.122
Authors: Christine L Chan; Iman Taki; Fran Dong; Michelle Hoffman; Jill M Norris; Georgeanna Klingensmith; Marian J Rewers; Andrea K Steck Journal: Diabetes Technol Ther Date: 2015-06-03 Impact factor: 6.118
Authors: Emily K Sims; Susan Geyer; Suzanne Bennett Johnson; Ingrid Libman; Laura M Jacobsen; David Boulware; Lisa E Rafkin; Della Matheson; Mark A Atkinson; Henry Rodriguez; Maria Spall; Helena Elding Larsson; Diane K Wherrett; Carla J Greenbaum; Jeffrey Krischer; Linda A DiMeglio Journal: Diabetes Care Date: 2019-09-26 Impact factor: 19.112
Authors: Maria J Redondo; Andrea K Steck; Jay Sosenko; Mark Anderson; Peter Antinozzi; Aaron Michels; John M Wentworth; Mark A Atkinson; Alberto Pugliese; Susan Geyer Journal: Diabetes Care Date: 2018-10-01 Impact factor: 19.112