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Inverse relationship between GAD65 antibody levels and severe retinopathy in younger type 1 diabetic patients

Agardh, Daniel LU ; Agardh, Elisabet LU ; Landin-Olsson, Mona LU ; Gaur, Lakshmi K; Agardh, Carl-David LU and Lernmark, Åke LU (1998) In Diabetes Research and Clinical Practice 40(1). p.9-14
Abstract
Several risk factors for severe non-proliferative and proliferative retinopathy in type 1 diabetes mellitus have been proposed without explaining the rapid progression of retinopathy in some patients. Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. Patients with severe non-proliferative or proliferative retinopathy (n = 27) were compared with another group, which in spite of long diabetes duration had no or only mild signs of retinopathy (n = 28). GAD65Abs were analysed in... (More)
Several risk factors for severe non-proliferative and proliferative retinopathy in type 1 diabetes mellitus have been proposed without explaining the rapid progression of retinopathy in some patients. Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. Patients with severe non-proliferative or proliferative retinopathy (n = 27) were compared with another group, which in spite of long diabetes duration had no or only mild signs of retinopathy (n = 28). GAD65Abs were analysed in a radioimmunoassay using in vitro translated human GAD65, and the levels were expressed as an index in relation to positive and negative reference samples. Using a cut-off level representing the 99th percentile of normals, 6/27 (22%) with and 9/28 (32%) without severe retinopathy were considered GAD65Ab positive. Although there was no difference in the number of GAD65Ab positive patients, the GAD65Ab levels were lower in patients with (0.30; 0.11-0.64) than without (0.68; 0.34-1.12) severe retinopathy (P = 0.03). The patients were also subjected to HLA-DR and DQ typing by PCR and hybridization with oligospecific probes. DQ2/8 was more common in patients with (56%) than without (29%) severe retinopathy (P = 0.05), but DQ2/8 could not account for the lower GAD65Ab levels in patients with severe retinopathy. It is concluded that GAD65Ab levels are inversely correlated with severe retinopathy in young type 1 diabetic patients. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GAD65Ab, Genotype, HLA-DR, HLA-DQ, Type 1 diabetes, Proliferative retinopathy
in
Diabetes Research and Clinical Practice
volume
40
issue
1
pages
9 - 14
publisher
Elsevier
external identifiers
  • pmid:9699085
  • scopus:0031869450
ISSN
1872-8227
DOI
10.1016/S0168-8227(98)00007-2
language
English
LU publication?
yes
id
9cc2ea3a-a92e-4f54-9560-5a28fc6b934b (old id 1112639)
date added to LUP
2008-07-10 10:56:21
date last changed
2017-01-01 04:44:14
@article{9cc2ea3a-a92e-4f54-9560-5a28fc6b934b,
  abstract     = {Several risk factors for severe non-proliferative and proliferative retinopathy in type 1 diabetes mellitus have been proposed without explaining the rapid progression of retinopathy in some patients. Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. Patients with severe non-proliferative or proliferative retinopathy (n = 27) were compared with another group, which in spite of long diabetes duration had no or only mild signs of retinopathy (n = 28). GAD65Abs were analysed in a radioimmunoassay using in vitro translated human GAD65, and the levels were expressed as an index in relation to positive and negative reference samples. Using a cut-off level representing the 99th percentile of normals, 6/27 (22%) with and 9/28 (32%) without severe retinopathy were considered GAD65Ab positive. Although there was no difference in the number of GAD65Ab positive patients, the GAD65Ab levels were lower in patients with (0.30; 0.11-0.64) than without (0.68; 0.34-1.12) severe retinopathy (P = 0.03). The patients were also subjected to HLA-DR and DQ typing by PCR and hybridization with oligospecific probes. DQ2/8 was more common in patients with (56%) than without (29%) severe retinopathy (P = 0.05), but DQ2/8 could not account for the lower GAD65Ab levels in patients with severe retinopathy. It is concluded that GAD65Ab levels are inversely correlated with severe retinopathy in young type 1 diabetic patients.},
  author       = {Agardh, Daniel and Agardh, Elisabet and Landin-Olsson, Mona and Gaur, Lakshmi K and Agardh, Carl-David and Lernmark, Åke},
  issn         = {1872-8227},
  keyword      = {GAD65Ab,Genotype,HLA-DR,HLA-DQ,Type 1 diabetes,Proliferative retinopathy},
  language     = {eng},
  number       = {1},
  pages        = {9--14},
  publisher    = {Elsevier},
  series       = {Diabetes Research and Clinical Practice},
  title        = {Inverse relationship between GAD65 antibody levels and severe retinopathy in younger type 1 diabetic patients},
  url          = {http://dx.doi.org/10.1016/S0168-8227(98)00007-2},
  volume       = {40},
  year         = {1998},
}