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Antibodies to glutamic acid decarboxylase and insulin-dependent diabetes in patients with autoimmune polyendocrine syndrome type I

Tuomi, Tiinamaija LU orcid ; Björses, Petra ; Falorni, Alberto ; Partanen, Jukka ; Perheentupa, Jaakko ; Lernmark, Åke LU orcid and Miettinen, Aaro (1996) In Journal of Clinical Endocrinology and Metabolism 81(4). p.1488-1494
Abstract

To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell antibodies, and HLA-DQA1, -DQB1, and -DRB1 were analyzed in relation to IDDM or a decreased insulin secretory capacity. GAD65-Ab were found in six of the eight diabetic patients 0.9-8.0 yr before the onset of IDDM and in 16 (41%) nondiabetic patients during a follow-up of 2.4-19.5 yr. Eleven (28%) nondiabetic patients had GAD67-Ab and islet cell antibodies. Fasting C peptide... (More)

To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell antibodies, and HLA-DQA1, -DQB1, and -DRB1 were analyzed in relation to IDDM or a decreased insulin secretory capacity. GAD65-Ab were found in six of the eight diabetic patients 0.9-8.0 yr before the onset of IDDM and in 16 (41%) nondiabetic patients during a follow-up of 2.4-19.5 yr. Eleven (28%) nondiabetic patients had GAD67-Ab and islet cell antibodies. Fasting C peptide (mean ± SD, 0.5 ± 0.24 vs. 1.03 ± 0.49 nmol/L; P = 0.003) and first phase insulin response (75.6 ± 37.9 vs. 166.4 ± 112.7 mU/L; P = 0.019) were lower in patients with than in those without GAD65-Ab. No HLA genotype predominated in the IDDM patients or GAD65-Ab-positive nondiabetic patients, but the IDDM high risk genotypes were decreased in frequency among the patients with GAD65-Ab. In conclusion, nondiabetic autoimmune polyendocrine syndrome type 1 patients frequently have GAD65-Ab together with a decreased insulin secretory capacity, suggesting subclinical islet cell inflammation not invariably progressing to diabetes. This is not associated with HLA haplotypes conferring susceptibility to or protection from IDDM.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
81
issue
4
pages
1488 - 1494
publisher
Oxford University Press
external identifiers
  • pmid:8636356
  • scopus:0029988330
ISSN
0021-972X
DOI
10.1210/jcem.81.4.8636356
language
English
LU publication?
yes
id
4a0b2196-c830-421d-9076-52fd4d5031b2
date added to LUP
2019-07-01 13:23:41
date last changed
2024-05-28 20:04:56
@article{4a0b2196-c830-421d-9076-52fd4d5031b2,
  abstract     = {{<p>To evaluate the association of autoimmunity to glutamic acid decarboxylase (GAD) with insulin-dependent diabetes mellitus (IDDM) and IDDM-associated human leukocyte antigen (HLA) types, we studied a unique group of 47 patients with autoimmune polyendocrine syndrome type 1, a recessive disease not associated with HLA. GAD65 antibodies (GAD65-Ab), GAD67-Ab, islet cell antibodies, and HLA-DQA1, -DQB1, and -DRB1 were analyzed in relation to IDDM or a decreased insulin secretory capacity. GAD65-Ab were found in six of the eight diabetic patients 0.9-8.0 yr before the onset of IDDM and in 16 (41%) nondiabetic patients during a follow-up of 2.4-19.5 yr. Eleven (28%) nondiabetic patients had GAD67-Ab and islet cell antibodies. Fasting C peptide (mean ± SD, 0.5 ± 0.24 vs. 1.03 ± 0.49 nmol/L; P = 0.003) and first phase insulin response (75.6 ± 37.9 vs. 166.4 ± 112.7 mU/L; P = 0.019) were lower in patients with than in those without GAD65-Ab. No HLA genotype predominated in the IDDM patients or GAD65-Ab-positive nondiabetic patients, but the IDDM high risk genotypes were decreased in frequency among the patients with GAD65-Ab. In conclusion, nondiabetic autoimmune polyendocrine syndrome type 1 patients frequently have GAD65-Ab together with a decreased insulin secretory capacity, suggesting subclinical islet cell inflammation not invariably progressing to diabetes. This is not associated with HLA haplotypes conferring susceptibility to or protection from IDDM.</p>}},
  author       = {{Tuomi, Tiinamaija and Björses, Petra and Falorni, Alberto and Partanen, Jukka and Perheentupa, Jaakko and Lernmark, Åke and Miettinen, Aaro}},
  issn         = {{0021-972X}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  pages        = {{1488--1494}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Clinical Endocrinology and Metabolism}},
  title        = {{Antibodies to glutamic acid decarboxylase and insulin-dependent diabetes in patients with autoimmune polyendocrine syndrome type I}},
  url          = {{http://dx.doi.org/10.1210/jcem.81.4.8636356}},
  doi          = {{10.1210/jcem.81.4.8636356}},
  volume       = {{81}},
  year         = {{1996}},
}