Imperial College London
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Dr Shivani Misra

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Senior Lecturer in Diabetes and Endocrinology
 
 
 
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Contact

 

s.misra

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Thomas:2022:10.1007/s00125-022-05823-1,
author = {Thomas, NJ and Walkey, HC and Kaur, A and Misra, S and Oliver, NS and Colclough, K and Weedon, MN and Johnston, DG and Hattersley, AT and Patel, KA},
doi = {10.1007/s00125-022-05823-1},
journal = {Diabetologia},
pages = {310--320},
title = {The relationship between islet autoantibody status and the genetic risk of type 1 diabetes in adult-onset type 1 diabetes},
url = {http://dx.doi.org/10.1007/s00125-022-05823-1},
volume = {66},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Aims/hypothesisThe reason for the observed lower rate of islet autoantibody positivity in clinician-diagnosed adult-onset vs childhood-onset type 1 diabetes is not known. We aimed to explore this by assessing the genetic risk of type 1 diabetes in autoantibody-negative and -positive children and adults.MethodsWe analysed GAD autoantibodies, insulinoma-2 antigen autoantibodies and zinc transporter-8 autoantibodies (ZnT8A) and measured type 1 diabetes genetic risk by genotyping 30 type 1 diabetes-associated variants at diagnosis in 1814 individuals with clinician-diagnosed type 1 diabetes (1112 adult-onset, 702 childhood-onset). We compared the overall type 1 diabetes genetic risk score (T1DGRS) and non-HLA and HLA (DR3-DQ2, DR4-DQ8 and DR15-DQ6) components with autoantibody status in those with adult-onset and childhood-onset diabetes. We also measured the T1DGRS in 1924 individuals with type 2 diabetes from the Wellcome Trust Case Control Consortium to represent non-autoimmune diabetes control participants.ResultsThe T1DGRS was similar in autoantibody-negative and autoantibody-positive clinician-diagnosed childhood-onset type 1 diabetes (mean [SD] 0.274 [0.034] vs 0.277 [0.026], p=0.4). In contrast, the T1DGRS in autoantibody-negative adult-onset type 1 diabetes was lower than that in autoantibody-positive adult-onset type 1 diabetes (mean [SD] 0.243 [0.036] vs 0.271 [0.026], p<0.0001) but higher than that in type 2 diabetes (mean [SD] 0.229 [0.034], p<0.0001). Autoantibody-negative adults were more likely to have the more protective HLA DR15-DQ6 genotype (15% vs 3%, p<0.0001), were less likely to have the high-risk HLA DR3-DQ2/DR4-DQ8 genotype (6% vs 19%, p<0.0001) and had a lower non-HLA T1DGRS (p<0.0001) than autoantibody-positive adults. In contrast to children, autoantibody-negative adults were more likely to be male (75% vs 59%), had a higher BMI (27 vs 24 kg/m2) and were less likely to have other autoimmune conditions (2% vs 10%) than autoantib
AU  - Thomas,NJ
AU  - Walkey,HC
AU  - Kaur,A
AU  - Misra,S
AU  - Oliver,NS
AU  - Colclough,K
AU  - Weedon,MN
AU  - Johnston,DG
AU  - Hattersley,AT
AU  - Patel,KA
DO  - 10.1007/s00125-022-05823-1
EP  - 320
PY  - 2022///
SN  - 0012-186X
SP  - 310
TI  - The relationship between islet autoantibody status and the genetic risk of type 1 diabetes in adult-onset type 1 diabetes
T2  - Diabetologia
UR  - http://dx.doi.org/10.1007/s00125-022-05823-1
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000882089400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://link.springer.com/article/10.1007/s00125-022-05823-1
UR  - http://hdl.handle.net/10044/1/104405
VL  - 66
ER  -
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