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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

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

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

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

Within the last decades multiple iodolipid-classes have been identified in thyroid tissue. For a long time they have been supposed to be involved in thyroid autoregulation, but for the time being no specific compounds could be isolated. A new approach was stimulated by the finding that thyroid cells were able to iodinate polyunsaturated fatty acids to form iodolactones and by the identification of alpha-iodohexadecanal (alpha-IHDA) as the major compound of an iodolipid fraction. alpha-IHDA exerts multiple inhibitory effects on adenylate cyclase, NADPH-oxidase and thyroid peroxidase. Therefore, it is speculated as a mediator of the Wolff-Chaikoff-effekt and to be involved in the autoregulation of specific thyroid functions mediated by the cyclic adenosine-3',5'-monophosphate (cAMP)-pathway. Meanwhile 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid delta-lactone (delta-iodolactone) has been identified in human thyroid tissue and it could be demonstrated that this iodoeicosanoid specifically inhibits signal transduction pathways induced by local growth factors such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Therefore, delta-iodol-actones seem to act as mediators of iodine, especially in the autoregulation of cAMP-independent thyroid cell proliferation. We will summarize these important new findings and discuss the role of these iodolipids on thyroid cell growth regulation.
Exp Clin Endocrinol Diabetes 1996
PMID:Iodolactones and iodoaldehydes--mediators of iodine in thyroid autoregulation. 898 Oct

Apart from genes in the HLA complex (IDDM1) and the variable number of tandem repeats in the 5' region of the insulin gene (INS VNTR, IDDM2), several other loci have been proposed to contribute to IDDM susceptibility. Recently, linkage and association have been shown between the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene on chromosome 2q and IDDM. In a registry-based group of 525 recent-onset IDDM patients <40 years old we investigated the possible interactions of a CTLA-4 gene A-to-G transition polymorphism with age at clinical disease onset and with the presence or absence of established genetic (HLA-DQ, INS VNTR) and immune disease markers (autoantibodies against islet cell cytoplasm (ICA); insulin (IAA); glutamate decarboxylase (GAD65-Ab); IA-2 protein tyrosine phosphatase (IA-2-Ab)) determined within the first week of insulin treatment. In new-onset IDDM patients. G-allele-containing CTLA-4 genotypes (relative risk (RR)= 1.5; 95% confidence interval (CI) = 1.2-2.0; P < 0.005) were not preferentially associated with age at clinical presentation or with the presence of other genetic (HLA-DR3 or DR4 alleles; HLA-DQA1*0301-DQB1*0302 and/or DQA1*0501-DQB1*0201 risk haplotypes; INS VNTR I/I risk genotype) or immune (ICA, IAA, IA-2-Ab, GAD65-Ab) markers of diabetes. For 151 patients, thyrogastric autoantibodies (anti-thyroid peroxidase, anti-thyroid-stimulating hormone (TSH) receptor, anti-parietal cell, anti-intrinsic factor) were determined, but association between CTLA-4 risk genotypes and markers of polyendocrine autoimmunity could not be demonstrated before or after stratification for HLA- or INS-linked risk. In conclusion, the presence of a G-containing CTLA-4 genotype confers a moderate but significant RR for IDDM that is independent of age and genetic or immune disease markers.
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PMID:CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. The Belgian Diabetes Registry. 935 55

The prevalence of thyroglobulin autoantibodies and that of thyroid peroxidase autoantibodies were studied in serum samples from 52 children with insulin-dependent diabetes mellitus, sampled at diagnosis and before the start of insulin treatment, with 386 non-diabetic schoolchildren (11 to 13 years of age) serving as control subjects. Using exactly the same sensitive solid-phase immunosorbent radioassay for both thyroid autoantibodies, with comparable sensitivity, we found the prevalences of both autoantibodies to be higher in the insulin-dependent diabetes mellitus group than in the control group, the difference being most pronounced for thyroid peroxidase autoantibodies. Thyroglobulin autoantibodies were positive in 33% of the diabetics versus 14% in the control group (p = 0.002), and thyroid peroxidase autoantibodies were positive in 38% versus 6% (p = 0.0001). The high prevalence of thyroid autoantibodies already at diagnosis stresses the importance of early screening for thyroid disease in patients with insulin-dependent diabetes mellitus.
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PMID:High prevalence of thyroid autoantibodies at diagnosis of insulin-dependent diabetes mellitus in Swedish children. 942 32

In the pathomechanism of the thyroid associated ophthalmopathy (TAO) the inflammatory cytokines produced by infiltrating lymphocytes of the retroorbital tissues are involved. The activated lymphocytes have been shown to secrete a number of cytokines including tumour necrosis factor-alpha, interleukin-1 and interferon-gamma. The widely used immunosuppressive therapies have potential serious side effects. The pentoxifylline (Ptx) is known to have effect on production of cytokines. The aim of this study was to investigate the effect of Ptx on expression of HLA-DR molecules and production of glycosaminoglycan of human retroorbital tissue cultures and potential efficacy in patients with TAO. It was found that pentoxifylline (Ptx) was able to inhibit significantly the HLA-DR expression and glycosaminoglycan synthesis induced by inflammatory cytokines including TNF-alpha, IFN-gamma and IL-1. Ten patients with untreated moderate severe ophthalmopathy (8 female and 2 male) were excluded from steroid treatment due diabetes mellitus and psychiatric disease. Classification of eye changes was made by NOSPECS categories and total eye score. All patients were euthyroid during the study and was no remarkable difference in thyroid function and eye symptoms. Before and during Ptx therapy the laboratory parameters were also determined including glycosaminoglycan. TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies in the patients'sera. It was found a remarkable improvement in the eye symptoms in eight of ten patients. The levels of glycosaminoglycan (uronic acid) and TNF-alpha gradually decreased in eight patients who considered to be responders. The levels of uronic acid in plasma of the responders were found to be significantly lower after Ptx treatment. Before Ptx therapy the TNF-alpha in the sera was not different remarkably in non-responders and responders. After 4 weeks Ptx treatment the TNF-alpha decreased significantly in responders compared to non-responders (20.9 +/- 4.8 pg/ml v. s. 28.3 +/- 6.1 pg/ml) (p < 0.01). The titre of anti-eye muscle antibodies were found to be lower at the end of observation, however, the anti-thyroid antibodies were not changed remarkably. It was concluded that Ptx in the majority of patients (8/10) has a beneficial effect on inflammatory symptoms of TAO and laboratory parameters and suggested to use as an additive therapy, however, further comparative studies are required for final evaluation of Ptx in the treatment of TAO.
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PMID:[Immunomodulatory effect of pentoxifylline in Graves ophthalmopathy]. 943 36


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