title: Challenges in developing endpoints for type 1 diabetes intervention studies.
abstract: Development of efficient and safe intervention strategies for preserving and/or restoring endogenous insulin production in type 1 diabetes has encountered a wide range of challenges, including lack of standardized trial protocols and of consensus on appropriate efficacy endpoints. For the greatest part, difficulties resided in choosing the most suitable assay(s) and parameter(s) to assess the beta-cell function. It is now an accepted approach to evaluate endogenous insulin secretion by measuring C-peptide levels (with highly sensitive and normalized measurement methods) in response to a physiologic stimulus (liquid mixed-meal) under standardized conditions. Preventive interventions mandate the identification of well-defined, reliable and validated mechanistic or immunological markers of efficacy that would correlate with (and predict) the clinical outcome. This has not been consistently achieved to date. However, it has been generally agreed that for preventive studies performed very early in the disease course (in subjects without signs of autoimmunity against beta-cells) development of two or more islet related autoantibodies could be employed as biomarkers of disease and thereafter, diagnostic criteria of diabetes serve as suitable endpoints.This report summarizes the conclusions of the D-Cure workshop of international experts held in Barcelona in April 2007 and the current recommendations and updates in the field.
authors.affiliation: Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cernea
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Boaz
authors.initials: B
authors.lastname: Hirshberg
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Desmond A
authors.initials: DA
authors.lastname: Schatz
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Fleming
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Randie
authors.initials: R
authors.lastname: Little
authors.forename: Nanette C
authors.initials: NC
authors.lastname: Schloot
authors.forename: R David G
authors.initials: RD
authors.lastname: Leslie
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
mesh_terms: D002096:C-Peptide / Q000097:blood*; D002986:Clinical Trials as Topic / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D023381:Endpoint Determination; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D009929:Organ Size
chemical_list: D002096:C-Peptide; D007328:Insulin