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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.
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PMID:Thyroid function and autoimmune manifestations in insulin-dependent diabetes mellitus during and after pregnancy. 202 11

Organ specific autoimmune diseases are relatively common immunological disorders in man which include thyroid autoimmune disease, insulin-dependent diabetes mellitus and myasthenia gravis. The target autoantigens in some of these diseases have recently been characterised. In thyroid autoimmune disease this includes the key enzyme, thyroid peroxidase (TPO), which is involved in the generation of thyroid hormone. Structural knowledge about autoantigens such as thyroid peroxidase will allow a greater understanding of the interaction between autoantigens and the aberrant immune response, and facilitate the development of strategies for antigen-specific therapeutic manipulation. We report here a prediction of the secondary structure of thyroid peroxidase, together with the results of circular dichroic spectroscopy of a homologous purified enzyme. A combination of 3 secondary structure prediction programs has been used, following multiple sequence alignment, and TPO has been found to consist mainly of alpha-helical conformation, with little beta-sheet present. This structure prediction, together with knowledge of the exon-intron boundaries allows a model for the domain organisation of the TPO molecule to be proposed.
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PMID:Prediction of domain organisation and secondary structure of thyroid peroxidase, a human autoantigen involved in destructive thyroiditis. 216 85

The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p less than 0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+-ATPase (3%) were all increased in the patients compared with the control children, being 2% (p less than 0.001), 2% (p less than 0.01), and 0.3% (p less than 0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.
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PMID:Islet cell and other organ-specific autoantibodies in all children developing type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children. 254 82

We have postulated over many years that autoimmune thyroid diseases (AITD) are disorders of immunoregulation due to antigen specific defect(s) in suppressor (regulatory) T (Ts) lymphocyte function. Despite earlier skepticism, there is recent increased evidence to support this view. Several investigators working with animal models have demonstrated T lymphocyte subsets that are regulatory, i.e., will prevent AITD; conversely, depletion of these cells precipitates the lesion in the experimental models. These cells have been shown to be inadequately activated by specific antigen. In human AITD, recent studies have demonstrated that CD8+ (suppressor/cytotoxic) and CD8+CD11b+ ("pure suppressor") cells are activated by irrelevant antigen normally, but are significantly less well activated in response to thyroglobulin or thyroperoxidase. In further similar studies, CD8+ cells from patients with Graves' disease (GD) are induced normally in response to glutamic acid decarboxylase-65 (GAD-65), the putative beta cell antigen important in insulin-dependent diabetes mellitus (IDDM), but significantly less to synthetic TSH receptor (TSHR). Conversely, CD8+ cells from patients with IDDM are activated normally in response to TSHR, but significantly less to GAD-65. While these reductions in activation are partial only, and other additive factors playing on the immune system may be necessary to precipitate AITD, this disorder in the activation of Ts cells may be fundamental to the development of these disorders. This in turn may be due to molecular disturbances in MHC-related genes that dictate the mechanisms of presentation of specific antigen.
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PMID:Immunoregulation in autoimmune thyroid disease. 783 79

Sera obtained at diagnosis from 273 children (0-14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment > 99% complete). Antibodies against glutamate decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-glutamate decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-glutamate decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (> or = 20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-glutamate decarboxylase. There was a higher frequency of anti-glutamate decarboxylase among girls than boys (75% vs 63%, p = 0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r = -0.41, p < 0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p = 0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-glutamate decarboxylase (p < 0.0001) and insulin autoantibodies (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study. 786 83

Recent evidence indicates that thyroid autoimmune disorders are associated with the presence of circulating autoantibodies (aAb) with dual specificity for thyroglobulin (TG) and thyroperoxidase (TPO). The question of whether these aAb, called TGPO aAb, are of clinical relevance compared to TG and TPO aAb remains to be determined. The availability of purified preparations of human TG and TPO allowed the development of a specific and sensitive RIA for TGPO aAb in serum. In the present study, we compared levels of aAb that cross-react with both TG and TPO (TGPO aAb) and total TG and TPO aAb levels, respectively, in sera from 84 normal controls and 226 patients with various thyroid and autoimmune diseases, including nontoxic goiter (n = 50), toxic nodular goiter (n = 13), thyroid carcinoma (n = 20), primary idiopathic myxedema (n = 15), postpartum thyroiditis (n = 11), Hashimoto's thyroiditis (n = 38), pernicious anemia (n = 27), rheumatoid arthritis (n = 19), and insulin-dependent diabetes mellitus (n = 33). In addition, 16 patients with Hashimoto's thyroiditis were studied before therapy and after more than 3 months of treatment with L-T4. It was shown that TGPO aAb were generally, but not always, present in the serum of patients with Hashimoto's thyroiditis, which also contained TG and TPO aAb. In contrast, TGPO aAb were undetectable in normal controls (excepting a few cases reaching borderline levels) as well as in sera from the majority of the other patients tested. Selecting sera positive for TGPO and either TG or TPO aAb, a statistically significant correlation was found between TGPO and TG (n = 26; P < 0.005), but not TPO aAb. Interestingly, the TGPO aAb level significantly decreased in patients with Hashimoto's thyroiditis after hormonal therapy (P < 0.05), some of them shifting from TGPO aAb positive before treatment to negative after treatment. In conclusion, TGPO aAb determination distinguishes Hashimoto's patients from patients with either thyroid and/or autoimmune diseases. The specific presence of TGPO aAb in a subset of Hashimoto's patients and their variation during T4 therapy remain to be understood. This could give a clue to mechanisms of autoimmune thyroid disease.
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PMID:Bispecific thyroglobulin and thyroperoxidase autoantibodies in patients with various thyroid and autoimmune diseases. 796 36

In 157 new onset IDDM (104 men, 53 women, ages 10-39 yr) anti-thyroid peroxidase anti-bodies (anti-TPO) were assayed with a specific immunological test. Values greater than 100 U ml-1 were considered positive. Seventeen per cent of the patients were positive (32% of the women versus 10% of the men, p < 0.001). Eighty-five per cent of the anti-TPO + patients have a positive titre of islet-cell antibodies (ICA > or = 12 JDFU) versus 64% of the anti-TPO-patients (p < 0.05). When patients were subdivided in a young (10-25 yr) and an older age group (26-39 yr) this association was also true for ICA > or = 50 JDFU and valid for insulin autoantibodies (IAA) at low (> or = 0.7%) and high risk (> or = 1.5%) (p < 0.005) in the second group. The median of the TSH concentration was not different between anti-TPO+ and anti-TPO- when the group is considered as a whole. In the anti-TPO+ men (26-39 yr) TSH was however significantly greater (1.55 microU ml-1, range 0.74-8.5 versus 1.4 microU ml-1, range 0.21-3.5, p < 0.0001) when compared to the anti-TPO-men of the same age group. The haplotype HLA DQA1*0301-DQB1*0302 was more frequent in the anti-TPO+ (39%) than in the anti-TPO- (23%) patients (p < 0.02) for the age group 26-39 yr but not for the age group 10-25 yr. The other diabetes susceptibility haplotype DQA1*0501-DQB1*0201 was less frequent in anti-TPO+ patients. In conclusion we suggest that thyroid auto-immunity must be part of the initial screening of IDDM especially when patients are older at clinical onset of the disease.
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PMID:In new-onset insulin-dependent diabetic patients the presence of anti-thyroid peroxidase antibodies is associated with islet cell autoimmunity and the high risk haplotype HLA DQA1*0301-DQB1*0302. Belgian Diabetes Registry. 873 22

Direct multi-colour flow cytometric analysis was employed in patients with Graves' disease (n = 10) to determine the immunophenotype in peripheral blood lymphocytes (PBL) at the time of diagnosis without treatment (PBLw) and prior to operation (PBLp) and in thyroid-derived lymphocytes (TL). Additionally, the secretion of anti-thyroperoxidase antibodies (anti-TPO) was measured during culture of isolated peripheral or thyroid-derived B cells. Among TL from patients with high serum levels of anti-TPO (6/10) a significantly (p < 0.01) higher percentage of B cells were detected compared to PBLp (TL: 21.7 +/- 7.2%; PBLp: 13.2 +/- 4.5%). Enriched thyroid-derived B cells only from these patients also showed high spontaneous anti-TPO secretion during culture. The difference between peripheral and thyroid-derived natural killer (NK) cells was highly significant (p < 0.001; TL: 5.6 +/- 6.3%; PBLp: 13.6 +/- 5.5%). Two patients were found with a higher number of NK cells within TL. These patients were among those who had a low number of B cells infiltrating the thyroid gland. Regarding the expression of several other differentiation antigens, i.e. CD4 and CD8, gamma/delta TCR bearing T cells and CD45R0 on CD4+ T cells as a marker for memory cells, on TL no differences could be detected between patients with or without anti-TPO. In TL 31.5 +/- 7.7% of CD3- cells expressed the HLA-DR antigen (vs. 6.1 +/- 2.4% in PBLp; p < 0.001). Half of these cells simultaneously expressed the activation antigen CD69. Surprisingly, the number of CD3+ TL bearing the IL-2 receptor (CD25) and transferrin receptor (CD71) was not increased. Taken together, the proportional distribution of B and NK cells within the thyroid correlates with the anti-TPO secretion in vivo and in vitro, suggesting different immune response regulation processes of TL.
Exp Clin Endocrinol Diabetes 1996
PMID:Different immunophenotype and autoantibody production by peripheral blood and thyroid-derived lymphocytes in patients with Graves' disease. 875 May 71

Anti-myeloperoxidase (anti-MPO) antibodies were detected in 34 of 88 (38%) patients with type 1 diabetes mellitus but in only 3 of 55 (5.7%) healthy subjects and in 4 of 20 patients with autoimmune disease. Specificity of anti-MPO antibodies was assessed by MPO inhibition studies. No relationship was found between the occurrence of anti-MPO and anti-thyroperoxidase antibodies. Levels of soluble intercellular adhesion molecule 1 (ICAM-1) were found to be higher in anti-MPO antibody-positive (n = 28, 508 +/- 126 ng/ml) than in anti-MPO antibody-negative (n = 58, 438 +/- 140 ng/ml: P < 0.05) patients. A state of chronic neutrophil activation has been described in diabetes mellitus. As anti-MPO antibodies can stimulate neutrophils to damage endothelial cells in systemic vasculitis, this suggests that a similar mechanism may be operative in the development of diabetic angiopathy.
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PMID:Detection of anti-myeloperoxidase antibodies in the serum of patients with type 1 diabetes mellitus. 887 Aug 10

Excess iodine ingestion has been implicated in induction and exacerbation of autoimmune thyroiditis in human populations and animal models. We studied the time course and sex-related differences in iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. This strain, derived from a cross of NOD with B10.A(4R), spontaneously develops autoimmune thyroiditis but not diabetes. NOD-H-2h4 mice were given either plain water or water with 0.05% iodine for 8 weeks. Approximately 54% of female and 70% of male iodine-treated mice developed thyroid lesions, whereas only 1 of 20 control animals had thyroiditis at this time. Levels of serum thyroxin (T4) were similar in the treatment and control groups. Thyroglobulin-specific antibodies were present in the iodine-treated group after 8 weeks of treatment but antibodies to thyroid peroxidase were not apparent in the serum of any of the animals. Levels of thyroglobulin antibodies increased throughout the 8-week iodine ingestion period; however, no correlation was seen between the levels of total thyroglobulin antibodies and the degree of thyroid infiltration at the time of autopsy. The thyroglobulin antibodies consisted primarily of IgG2a, IgG2b, and IgM antibodies with no detectable IgA, IgG1, or IgG3 thyroglobulin-specific antibodies. The presence of IgG2b thyroglobulin-specific antibodies correlated well with the presence of thyroid lesions.
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PMID:Iodine-induced autoimmune thyroiditis in NOD-H-2h4 mice. 893 7


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