Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reverse transcriptase- polymerase chain reaction (RT-PCR) enhances the probability of detecting rare transcripts in complex mixtures of mRNA. Using thyroid autoantigens and the controversy about the role of the TSH-receptor (TSH-R) in thyroid-associated ophthalmopathy as an example, this study demonstrates the problems of interpreting RT-PCR results in typically non-expressing tissues resulting from the extremely high sensitivity of the method. Unexpected transcripts for thyroperoxidase, thyroglobulin, TSH-R (exon 1-4, 354 bp), FSH-receptor, or insulin fragments were demonstrated in a number of thyroid or orbit-derived as well as unrelated tissues or cell types. Unexpected transcripts were most prevalent in fibroblasts, irrespective of the tissue of origin and most likely caused by ectopic transcription. To establish a physiological significance of rare transcripts such as the TSH-R in orbital tissues, demonstration of the protein in addition to the positive RT-PCR results is needed.
Exp Clin Endocrinol Diabetes 1998
PMID:Transcription of thyroid autoantigens in non-expressing tissues. 979 65

By coupling 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)dione (MECH) to divinyl sulfone activated agarose, a novel thiophilic matrix was obtained which allows the binding of immunoglobulins from different sources. In contrast to other thiophilic gels, antibodies are bound at low ionic strength and can easily be desorbed in intact form by elution with dilute alkali. The potential of using the MECH-gel was demonstrated by the purification of antibodies from human and animal (goat, rabbit, mouse) sera. The functional integrity of the purified antibodies was established with cytoplasmic islet cell antibodies from the sera of patients with type I diabetes and autoantibodies against thyroid peroxidase from patients with Graves' and Hashimoto's disease.
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PMID:A simplified procedure for the isolation of immunoglobulins from human serum using a novel type of thiophilic gel at low salt concentration. 983 92

Sideropenia affects ca. 20% of the world population, and iron dependent anemia is the most frequent type of anemia worldwide. The aim of the study was to investigate the incidence of sideropenia and dependent anemia in patients with subtle changes of the thyroid function, such as subclinical hypothyroidism (SH). 57 women with SH and 61 euthyroid controls (CG) were studied. Serum concentrations of T4, T3, TSH, anti-TPO, anti-Tg, ferrum (Fe), ferritin (Frt) total iron binding capacity (TIBC) and blood count were determined. In SH 17 patients (29.8%) presented low Fe levels (<50 microg/dl). 9 (15.7%) also had decreased Frt, confirming iron deficiency, whereas 8 patients presented additionally diminished hematocrit and hemoglobin levels, suggesting manifested sideropenic anemia. In CG, 10 persons (16%) had sideropenia, 6 (9.8%) had low Fe and Frt and only 3 (4.9%) had blood count alterations suggesting manifested sideropenic anemia. In SH, anti-TPO were positive in 39 patients (68%), whereas, in CG only 2 (3.2%) were positive. 8 patients with SH and manifested sideropenic anemia were treated with ironproteinsuccinylate (I-PSL), (80 mg Fe /day, for three months), a new iron compound. The repletion treatment safely led to the clinical and laboratory correction of sideropenia and showed a good tolerability. Furthermore, iron treatment provoked a minor increase of T4 and a mild decline of TSH, but the levels were not significant. These results suggest that sideropenia is a common finding in patients with slightly decreased thyroid activity, and that determination of Frt should be routinely advised. Finally, in the assessment of sideropenia and dependent anemia, evaluation of the thyroid function must be taken into account.
Exp Clin Endocrinol Diabetes 1999
PMID:Incidence of sideropenia and effects of iron repletion treatment in women with subclinical hypothyroidism. 1054 12

First-degree relatives of type 1 diabetic patients are at increased risk of developing diabetes and, until recently, islet cell antibodies (ICA) have represented the major risk marker used for identification of individuals at increased risk for subsequent progression to diabetes. In order to determine the value of antibodies to GAD-65 and IA-2ic to identify individuals at high risk for type 1 diabetes mellitus, we measured both autoantibodies and ICA in 1436 first-degree relatives of patients with type 1 diabetes. In addition, the sera were analyzed for thyroid, adrenal and gastric-parietal cell autoantibodies as markers for possible polyendocrine involvement. GAD-65 Abs were found in 135 out of 1436 (9.4%) first-degree relatives and in 57 of 98 (58.2%) ICA-positive subjects. IA-2ic were detected in 52 of 1436 (3.6%) first-degree relatives and in 44 of 98 (44.8%) ICA-positive relatives. IA-2ic and/or GAD-65 were detected in 73 of 98 (74.5%) ICA-positive relatives. Interestingly, antibodies to GAD-65 and/or IA-2ic were present in 91.2% of individuals with more than 20JDF-units. Anti-IA-2ic and GAD-65 were positively correlated with high levels of ICA. Anti-IA-2ic and GAD-65 were found in 19% and 48.5% of subjects with ICA levels of 5-20JDF-u but in 68.8% and 76.5% of individuals with ICA of 40JDF-u or more, respectively (p < 0.001), compared to subjects with ICA levels less than 5 JDF-u. When autoantibody frequencies among the relatives were analyzed according to relationship to the proband, the offspring and siblings had a higher frequency of ICA and IA-2ic (p<0.05) than the subgroup of parents. A significant association was observed between IA-2ic and thyroid antibodies. In addition, higher levels of IA-2ic were found in relatives with positive TPO antibodies (p < 0.001); this correlation was particularly strong in offspring and siblings (p < 0.01). Determination of GAD-65 and IA-2ic antibodies may be considered as an alternative to primary ICA-screening, enabling the screening of large populations.
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PMID:The combination of antibodies to GAD-65 and IA-2ic can replace the islet-cell antibody assay to identify subjects at risk of type 1 diabetes mellitus. 1059 66

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr. The presence of GAD65Ab (61/569, 10.7%) depended on insulin therapy (P<0.0001), low BMI (P<0.0001), and low basal C-peptide (P = 0.01). The majority of GAD65Ab-positive subjects (47/61, 77%) had antibodies directed to both middle (GAD65-MAb) and COOH-terminal (GAD65-CAb) epitopes. However, GAD65-CAb were more frequent in insulin-treated subjects (92% of GAD65Ab+ individuals) than in subjects treated with hypoglycemic agents and/or diet (18.2% of GAD65Ab+ individuals), while the exclusive presence of GAD65-MAb was more frequent in subjects treated with hypoglycemic agents and/or diet (81.8% vs. 8%) (P<0.0001). The presence of GAD65-CAb had a diagnostic specificity for insulin requirement as high as 99.4% (compared with 96.9% of GAD65Ab as measured in the traditional radiobinding assay) and identified a subgroup of patients with low BMI, low basal C-peptide values, and a need for insulin therapy. Subjects carrying only GAD65-MAb were phenotypically indistinguishable from GAD65Ab-negative patients. Patients positive for GAD65-M+CAb, but not those positive for GAD65-MAb only, showed an increased risk for thyroid autoimmunity, as revealed by the presence of thyroid peroxidase autoantibodies. Our study demonstrates that the use of epitope-specific antibody assays improves the diagnostic specificity of GAD65Ab, and that the presence of GAD65Ab binding to COOH-terminal epitopes is strongly associated with a need for insulin requirement.
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PMID:Autoantibody recognition of COOH-terminal epitopes of GAD65 marks the risk for insulin requirement in adult-onset diabetes mellitus. 1063 4

Type 1 diabetes is often associated with additional autoimmune phenomena. However, data reported on the frequency of thyroid autoimmunity differ vastly. Therefore, the prevalence of thyroid autoantibodies was evaluated at a large pediatric diabetes center in Southern Germany. 2,305 determinations (TPO and TG, ELISA) were performed in 495 patients with type 1 diabetes (234 boys, 261 girls; age at last measurement: 15.4 +/- 0.3 years, duration of diabetes 7. 5 +/- 0.2 years). The prevalence of elevated thyroid antibodies increased dramatically with age: from 3.7% in patients less than 5 years of age up to 25.3% in the age group 15-20 years (p < 0.0001). For children older than 10 years, girls were significantly more affected than boys (p < 0.0001). Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). In children older than 10 years, basal TSH concentrations were significantly elevated in antibody-positive patients (p < 0.05). In conclusion, thyroid autoimmunity is prevalent in children and adolescents with type 1 diabetes. Adolescent girls and young women are especially affected. Yearly routine determinations of thyroid antibodies are therefore recommended.
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PMID:Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Effect of age, gender and HLA type. 1072 74

Impairment of thyroid function has been described in up to 50% of the patients after external irradiation of the neck region as well as after mantle irradiation. In order to assess radiation-induced alterations in cultured thyroid cells, the occurrence of apoptosis and necrosis as well as the expression of thyroid peroxidase (TPO) and of two members of the 70 kD heat shock family, HSP-73 and HSP-72, were analysed following gamma irradiation. Human thyroid epithelial cells (TEC) were purified from surgical tissue specimens, were cultured and irradiated with a single dose of 5 Gy or 50 Gy using Co60 as radioactive source. Analysis was performed 1, 3 and 5 day(s) after irradiation. Apoptosis and necrosis were assessed by DNA staining with propidium iodide and FACS analysis. TPO and HSP expression by SDS-PAGE and Western blotting. The cell viability of TEC was not affected by irradiation and there was no induction of HSP-72, a sensitive indicator of acute cellular stress. Interestingly, the expression of TPO, a key enzyme of thyroid hormone synthesis, decreased significantly in irradiated TEC, while HSP-73 expression remained unchanged. Decreased expression of TPO with a resulting suppression of thyroid hormone synthesis could contribute to an early development of thyroid dysfunction following irradiation. Thus, analysis of thyroid function, even early after external radiation therapy of the neck or after total body irradiation, seems to be indicated.
Exp Clin Endocrinol Diabetes 2000
PMID:Decreased thyroid peroxidase expression in cultured thyrocytes after external gamma irradiation. 1082 22

Autoimmune type 1 diabetic patients show a high prevalence of thyroid peroxidase (TPO), parietal cell (PCA), anti-adrenal (AAA) and anti-endomysium antibodies (EmA-IgA), which may be accompanied with clinical disease. We studied the grade of associated organ-specific autoimmunity and the pattern of prevalence of TPO and PCA by age, gender, duration, age at onset of diabetes, and HLA DR haplotype in 783 type 1 diabetic patients, consisting of 286 children and 497 adults (M/F: 389/394), with a mean diabetes duration of 11.8 +/- 10.1 years. The relationship between islet cell (ICA), glutamic acid decarboxylase-65 (GADA) and thyro-gastric auto-antibodies was also investigated. TPO were present in 21.6%, PCA in 18.3%, AAA in 2.2% and EmA-IgA in 2.1% of the patients. The presence of TPO is determined by gender (p < 0.0001), age (P = 0.0008), and PCA status (p = 0.029). The presence of PCA is only influenced by age (p = 0.0027) and TPO status (p = 0.0155). Patients with ICA+ > or = 3 years had a higher prevalence of thyro-gastric auto-antibodies (p = 0.045) than ICA- subjects. Also, PCA were more prevalent in GADA+ than GADA- patients (p = 0.005). We observed an association between HLA DR5 and PCA (p = 0.0012). Dysthyroidism was more prevalent in TPO+ than TPO- subjects (p < 0.0001). PCA+ subjects had a higher prevalence of iron deficiency anaemia (p = 0.0099) and pernicious anaemia (p < 0.0001) than PCA- patients. In conclusion, particularly type 1 diabetic patients with persisting ICA > or = 3 years or with GADA, show a high prevalence of thyro-gastric auto-antibodies. Based on antibody-positivity we observed a high prevalence of thyroid disease, iron deficiency anaemia and pernicious anaemia, which can compromise the health of the diabetic patient.
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PMID:[Diabetes mellitus type 1 and associated organ-specific autoimmunity]. 1100 7

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p = 0.003, and 69 vs. 27%, p < 0.00, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-I patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRB1*03-DQB1* 02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1*13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD.
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PMID:Gliadin antibodies in adult insulin-dependent diabetes--autoimmune and immunogenetic correlates. 1119 Dec 81

Type 1 diabetes mellitus is an autoimmune disease in which the presence of different autoantigens can often be found. The aim of our study was to evaluate the prevalence of antibodies against insulin (IA) and autoantibodies against glutamic acid decarboxylase (anti-GAD), tyrosine phosphatase IA-2 (anti-IA-2), thyroid microsomal peroxidase (anti-TPO) and thyroglobulin (anti-TG) in 55 randomly selected Type 1 diabetic patients (34 males, 21 females). Mean age of these patients was 39 +/- 12 yrs, mean duration of diabetes 18 +/- 13 yrs. Positivity of anti-GAD was found in 29 (58%) patients, anti-IA-2 in 13 (25%) patients, IA in 46 (85%) patients, anti-TPO in 10 (21%) and anti-TG in 11 (23%) patients. Simultaneous positivity of thyroid and islet autoantibodies was found in 6 (11%) patients whereas the positivity at least one of them was in 38 (69%) patients. No relationship between glycated hemoglobin and autoantibody concentration was found in the whole group of patients. The autoimmune thyroid disease was newly detected in 4 patients from high concentration of thyroid autoantibodies together with impaired TSH and T4 values and ultrasonography finding. No clinical evidence of thyroid disease was previously found in these patients. Positivity of anti-GAD or anti-IA-2 was found in almost 65% and of any thyroid autoantibody in almost 30% of our patients. Four patients with autoimmune thyroid disease were newly identified. We conclude that the evaluation of thyroid autoantibodies in Type 1 diabetic patients may improve the diagnosis of thyroid disease in very early stage and thus prevent consequent complications.
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PMID:The evaluation of thyroid and islet autoantibodies in type 1 diabetes mellitus. 1122 67


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