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Characteristics of slow progression to diabetes in multiple islet autoantibody-positive individuals from five longitudinal cohorts: the SNAIL study
Univ Bristol, England.
Univ Bristol, England.
Univ Pittsburgh, PA 15260 USA.
Univ Pittsburgh, PA 15260 USA.
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2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 6, p. 1484-1490Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Multiple islet autoimmunity increases risk of diabetes, but not all individuals positive for two or more islet autoantibodies progress to disease within a decade. Major islet autoantibodies recognise insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A). Here we describe the baseline characteristics of a unique cohort of slow progressors (n = 132) who were positive for multiple islet autoantibodies (IAA, GADA, IA-2A or ZnT8A) but did not progress to diabetes within 10 years. Methods Individuals were identified from five studies (BABYDIAB, Germany; Diabetes Autoimmunity Study in the Young [DAISY], USA; All Babies in Southeast Sweden [ABIS], Sweden; Barts Oxford Family Study [BOX], UK and the Pittsburgh Family Study, USA). Multiple islet autoantibody characteristics were determined using harmonised assays where possible. HLA class II risk was compared between slow progressors and rapid progressors (n = 348 diagnosed amp;lt; 5 years old from BOX) using the chi(2) test. Results In the first available samples with detectable multiple antibodies, the most frequent autoantibodies were GADA (92%), followed by ZnT8A (62%), IAA (59%) and IA-2A (41%). High risk HLA class II genotypes were less frequent in slow (28%) than rapid progressors (42%, p = 0.011), but only two slow progressors carried the protective HLA DQ6 allele. Conclusion No distinguishing characteristics of slow progressors at first detection of multiple antibodies have yet been identified. Continued investigation of these individuals may provide insights into slow progression that will inform future efforts to slow or prevent progression to clinical diabetes.

Place, publisher, year, edition, pages
SPRINGER , 2018. Vol. 61, no 6, p. 1484-1490
Keywords [en]
HLA class II; Islet autoantibodies; Slow progression; Type 1 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:liu:diva-147895DOI: 10.1007/s00125-018-4591-5ISI: 000431650800024PubMedID: 29532109OAI: oai:DiVA.org:liu-147895DiVA, id: diva2:1209637
Note

Funding Agencies|Diabetes UK-Fulbright Award; Diabetes UK Moffat Travelling Fellowship [13/0004636]; Diabetes UK [14/0004869]; JDRF [17-2013-529, 17-2013-535]; Deutsche Forschungsgemeinschaft (DFG) [ZI-310/14-1]; National Institutes of Health (NIH) [R01 DK32083, DK32493]; Vetenskapsradet; Novo Nordisk; Barndiabetesfonden; ALF grants; Region Ostergotland and Medical Research Council of southeast Sweden (Forskningsradet i sydostrasverige, FORSS) [12594]; NIH [R01 DK53456, DK56200, R01 DK24021]; NIDDK [PA-04-081]; Brehm Coalition by the University of Michigan Center for Computational Medicine and Biology Pilot Research Program NIH Grant [R01 DK46864]; General Clinical Research Center of the Childrens Hospital of Pittsburgh Grant [MO1 RR 00084]; Renziehausen fund

Available from: 2018-05-23 Created: 2018-05-23 Last updated: 2019-05-01

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Ludvigsson, Johnny

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Division of Children's and Women's healthFaculty of Medicine and Health SciencesH.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus
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