Antibodies to glutamic acid decarboxylase and insulin-dependent diabetes in patients with autoimmune polyendocrine syndrome type I
(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.
(Less)
- author
- Tuomi, Tiinamaija LU ; Björses, Petra ; Falorni, Alberto ; Partanen, Jukka ; Perheentupa, Jaakko ; Lernmark, Åke LU and Miettinen, Aaro
- organization
- publishing date
- 1996-04-22
- 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}}, }