Imperial College London
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ProfessorNickOliver

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Wynn Chair in Human Metabolism (Clinical)
 
 
 
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Contact

 

+44 (0)20 7594 1796nick.oliver

 
 
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Location

 

7S7aCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Grace:2022:clinem/dgac507,
author = {Grace, SL and Bowden, J and Walkey, HC and Kaur, A and Misra, S and Shields, BM and McKinley, TJ and Oliver, NS and McDonald, T and Johnston, DG and Jones, AG and Patel, KA},
doi = {clinem/dgac507},
journal = {Journal of Clinical Endocrinology and Metabolism},
pages = {E4341--E4349},
title = {Islet autoantibody level distribution in Type 1 diabetes and their association with genetic and clinical characteristics},
url = {http://dx.doi.org/10.1210/clinem/dgac507},
volume = {107},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ContextThe importance of the autoantibody level at diagnosis of type 1 diabetes (T1D) is not clear.ObjectiveWe aimed to assess the association of glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) autoantibody levels with clinical and genetic characteristics at diagnosis of T1D.MethodsWe conducted a prospective, cross-sectional study. GADA, IA-2A, and ZnT8A were measured in 1644 individuals with T1D at diagnosis using radiobinding assays. Associations between autoantibody levels and the clinical and genetic characteristics for individuals were assessed in those positive for these autoantibodies. We performed replication in an independent cohort of 449 people with T1D.ResultsGADA and IA-2A levels exhibited a bimodal distribution at diagnosis. High GADA level was associated with older age at diagnosis (median 27 years vs 19 years, P = 9 × 10−17), female sex (52% vs 37%, P = 1 × 10−8), other autoimmune diseases (13% vs 6%, P = 3 × 10−6), and HLA-DR3-DQ2 (58% vs 51%, P = .006). High IA-2A level was associated with younger age of diagnosis (median 17 years vs 23 years, P = 3 × 10−7), HLA-DR4-DQ8 (66% vs 50%, P = 1 × 10−6), and ZnT8A positivity (77% vs 52%, P = 1 × 10−15). We replicated our findings in an independent cohort of 449 people with T1D where autoantibodies were measured using enzyme-linked immunosorbent assays.ConclusionIslet autoantibody levels provide additional information over positivity in T1D at diagnosis. Bimodality of GADA and IA-2A autoantibody levels highlights the novel aspect of heterogeneity of T1D. This may have implications for T1D prediction, treatment, and pathogenesis.
AU  - Grace,SL
AU  - Bowden,J
AU  - Walkey,HC
AU  - Kaur,A
AU  - Misra,S
AU  - Shields,BM
AU  - McKinley,TJ
AU  - Oliver,NS
AU  - McDonald,T
AU  - Johnston,DG
AU  - Jones,AG
AU  - Patel,KA
DO  - clinem/dgac507
EP  - 4349
PY  - 2022///
SN  - 0021-972X
SP  - 4341
TI  - Islet autoantibody level distribution in Type 1 diabetes and their association with genetic and clinical characteristics
T2  - Journal of Clinical Endocrinology and Metabolism
UR  - http://dx.doi.org/10.1210/clinem/dgac507
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000860685800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://academic.oup.com/jcem/article/107/12/e4341/6693901
UR  - http://hdl.handle.net/10044/1/104408
VL  - 107
ER  -
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