UMLS:C0011854 - FACTA Search

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Query: UMLS:C0011854 (type 1 diabetes)
20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four cases of polyglandular endocrine disorders associated with pituitary hormone secretion failure are reported. Three of them had both insulin dependent diabetes mellitus (IDDM) and Hashimoto's disease. Each of these patients (cases 1-3) showed isolated deficiency of ACTH, TSH or gonadotropin, respectively. Another patient (case 4) had both Hashimoto's disease and isolated ACTH deficiency. Anti-pituitary antibody to AtT-20 cells was detected in case 1. Serum gamma-globulins from patients 1 and 4 attenuated corticotropin releasing hormone-induced ACTH release in monolayer cultured rat anterior pituitary cells. Gamma-globulins from patients 1 and 2 decreased baseline TSH release but stimulated baseline prolactin release in pituitary cell cultures. It is possible that pituitary hormone deficiency in these patients may be caused by autoimmune disorders.
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PMID:Four patients with polyendocrinopathy with associated pituitary hormone deficiency. 753 23

We have postulated that a defect in specific antigenic induction of suppressor T lymphocytes may account for the immunoregulatory disorder in autoimmune thyroid disease. In this context, we have measured the proliferative responses of peripheral blood mononuclear cells (PBMC) to the synthetic peptides corresponding to the extracellular domain of the TSH receptor (TSHR) and recombinant glutamate decarboxylase (GAD65) by means of 3H thymidine incorporation. We have also studied the antigenic activation of CD4+ and CD8+ T lymphocytes by measuring human leukocyte antigen-DR (HLA-DR) expression on the cell surface by flow cytometric analysis. PBMC obtained from 47 patients with Graves' disease (GD) [including 19 hyperthyroid GD (hyper GD)], 18 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), 18 with insulin-dependent diabetes (IDDM), and 20 normal controls (N), were cultured for 7 days in the presence or absence of the pool peptides representing 3 different segments of TSHR or GAD65 at final concentration of 30 micrograms/mL or 10 micrograms/mL. The proportion of subjects whose PBMC gave a positive proliferative response with a stimulation index (SI) of over 2.3 (i.e. above the mean +2 SD for N) to TSHR peptides was significantly higher in the hyper GD group than among euthyroid GD (eu GD), HT, IDDM, and N group. The corresponding differences in mean SI provided analogous results, showing significant responses above normal in only hyper GD. The CD4+ T lymphocytes from hyper GD group were significantly more activated by TSHR peptides compared to eu GD, HT, IDDM, and N, and this induction correlated to their thyroid hormone levels. Quite differently, the activation of CD8+ T lymphocytes from both hyper GD and eu GD group in response to TSHR peptides was impaired compared to HT, IDDM, and the N group; in contrast to the findings with CD4+ T lymphocytes, this was independent of thyroid hormone levels. On the other hand, while the CD8+ T lymphocytes from GD and N groups were activated equally by GAD65, the activation of CD8+ T lymphocytes from the IDDM group by GAD65 was impaired compared to the GD and N groups. In conclusion, the activation of CD8+ T lymphocytes from GD and IDDM by relevant antigens (i.e. TSHR peptides for GD and GAD65 for IDDM) was impaired, but not by irrelevant antigens (i.e. GAD65 for GD and TSHR peptides for IDDM). There was also a modest stimulation of CD8+ T cells from all groups by tetanus toxoid and cardiac myosin light chain peptide, both irrelevant antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Activation of T lymphocyte subsets by synthetic TSH receptor peptides and recombinant glutamate decarboxylase in autoimmune thyroid disease and insulin-dependent diabetes. 771 99

In 129 children, aged 12.6 +/- 3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4, rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; -0.36 +/- 0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485 +/- 94 vs 359 +/- 132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 +/- 0.4 vs 2.32 +/- 0.3 nmol/l) and a higher rT3/T3 ratio (0.17 +/- 0.09 vs 0.15 +/- 0.05) than controls. There was a negative correlation between T3 and HbA1C. Cholesterol (4.77 +/- 1.08 vs 4.51 +/- 0.76 mmol/l) and triglycerides (0.82 +/- 0.53 vs 0.63 +/- 0.37 g/L) levels were higher in diabetic children and positively correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other illnesses.
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PMID:Altered adrenal and thyroid function in children with insulin-dependent diabetes mellitus. 782 51

A considerable proportion of endocrine disorders (Graves' disease, primary hypothyroidism, type 1 diabetes, Addison's disease, and some forms of ovarian failure) are due to aberrant reactions of the immune system, viz. exaggerated reactions towards self-structures (autoantigens). Autoreactive T-cells are mainly responsible for the elicitation of destructive inflammatory responses in the target endocrine glands. Autoantibodies play a minor role in such reactions, but are useful in clinical practice as markers of the disease. A special type of autoantibody is formed by those autoantibodies that have endocrine functional activity, viz. autoantibodies capable of stimulatory or blocking the hormone synthesis and/or the growth of endocrine cells. These autoantibodies interfere with receptors, e.g. the TSH receptor or the IGF-I receptor. Antibodies stimulating the TSH receptor are responsible for the hyperthyroidism of Graves' disease.
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PMID:Endocrine autoimmune diseases. 783 45

Insulin dependent diabetes mellitus (IDMM) is often associated with autoimmune thyroiditis (AIT) and a high prevalence of thyroid antibodies (TA). Ultrasound imaging of the thyroid may contribute to the evaluation of patients with AIT. We therefore investigated ultrasound findings of the thyroid in 83 IDDM patients (44F, 39M) with an age range of 2.3-22.3 yrs (median 11.1). Thyroid volume (ml) determined by ultrasound ranged between 1.3 and 17.9 (median 5.7). Thyroid volumes of 75 healthy children (32F, 43M) with an age range of 2.0 to 11.8 yrs (median 7.6) ranged between 1.6 and 13.2 ml (median 4.8) and did not show a significant difference from the IDDM group from age 4 to 12. TA were positive in 18.8% of the IDDM group. Thyroid volume was higher in TA (+) diabetics (p = 0.05), a finding which may be attributed to a higher percentage of cases with elevated TSH in the TA (+) group. Two diabetic patients showed non-homogeneous hypoechogenicity in the ultrasound compatible with AIT which was later confirmed in one of these cases by aspiration biopsy. Ultrasound imaging of the thyroid may contribute to the evaluation of patients with AIT in IDDM.
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PMID:Thyroid ultrasound in IDDM. 791 May 7

Postpartum thyroid dysfunction (PPTD) is a common autoimmune disorder. Type I diabetes mellitus (IDDM) is an autoimmune disease with a high incidence of concomitant autoimmune thyroid failure. We hypothesized that women with IDDM would have an increased incidence of PPTD. Women with IDDM in New York City, were followed prospectively during the second and third trimester of pregnancy and at 6 weeks, 3 months, 6 months, 9 months, and 1 yr postpartum. A long-term follow-up was performed at 31 months postpartum. Forty-one women with IDDM were recruited at their initial prenatal visit. Two women (4.8%) had thyroid function test abnormalities observed at screening, three (7.3%) had a spontaneous miscarriage, and eight (19.5%) women were noncompliant with follow-up. Twenty-eight women (68.2%) completed the study. Thyroid function tests and thyroid autoantibody determinations were obtained at all visits. PPTD was defined as a TSH greater than 5.0 or less than 0.2 mU/L in the postpartum period with documented normal thyroid function tests during pregnancy. The incidence of PPTD in women with IDDM was 25%. This is a 3-fold increase compared to a similar study by our group in a nondiabetic population. Forty-three percent of the women (3/7) who developed PPTD required treatment in the immediate postpartum period and at long-term follow-up. The remainder of the women with PPTD, as well as all women who did not develop PPTD were euthyroid at 31 months postpartum. Women with IDDM are at high risk for PPTD. We recommend that all women with IDDM be screened for thyroid hormonal abnormalities during pregnancy and at 3 months postpartum for postpartum thyroid dysfunction. Long-term follow-up did not reveal an increased incidence of hypothyroidism in women who did not require treatment in the first postpartum year.
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PMID:Long-term prospective study of postpartum thyroid dysfunction in women with insulin dependent diabetes mellitus. 802 56

Fifteen IDDM patients were evaluated for thyroid hormone abnormalities before and after control of diabetes mellitus/ketoacidosis. Blood sugar mean +/- SEM mg/dl on admission was 430 +/- 20.3 and after therapy fasting and post prandial blood sugar values were 120 +/- 14.5 and 150 +/- 20.2 respectively. GHb mean +/- SEM % on admission was 15.2 +/- 0.36. Serum T3 mean +/- SEM ng/dl of 0.36 +/- 0.04 was in hypothyroid range and rT3 mean +/- SEM ng/ml 0.40 +/- 0.6 was significantly raised (P < 0.001) before therapy. After metabolic control both T3 and rT3 became normal. T4 concentration mean +/- SEM meg/dl of 5.5 +/- 0.7 was well within normal range before therapy and rose to mean +/- SEM mcg/dl 8.8 +/- 0.5 after therapy (P < 0.01). TSH response to TRH was blunted in uncontrolled state. It is concluded that peripheral changes in T3, T4 and rT3 (low T3, high rT3 and low or normal T4) occurred in uncontrolled diabetic state during ketoacidosis. TSH response to TRH was blunted due to suppression of hypothalamic pituitary thyroid axis which takes more than a week for complete recovery.
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PMID:Thyroid hormones in diabetic ketoacidosis before and after therapy. 830 Apr 81

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

The objective of this paper was to determine the effect of glycaemic control and endocrine functions on linear growth in children with IDDM. We studied 45 prepubertal children with IDDM (30 males, 15 females) over 1 year period. The mean +/- SD for age of onset and duration of IDDM were 6.2 +/- 2.3 years and 3.5 +/- 1.3 years, respectively. At each clinic visit (every 3 months), glycaemic control was assessed by measuring glycosylated haemoglobin (HbA1C). Growth hormone and cortisol responses to high dose clonidine (0.15 mg/m2) and ACTH, respectively, were evaluated and circulating concentrations of free thyroxine (FT4) and TSH estimated. The average insulin dose (unit/kg/day) during this period was calculated for each patient. Growth was assessed by determining both height standard deviation score (HtSDS) and growth velocity standard deviation scores (GVSDS) and bone age determined according to the atlas of Greulich and Pyle. Two-hundred-and-fifty age- and sex-matched normal children served as controls for growth data, and 20 normal age-matched children and 20 normal children with short stature (NVSS) served as controls for the hormonal studies. Growth velocity (GV) (cm/year) and GVSDS were significantly lower in children with IDDM compared to normal children, and significantly lower in children with poorly controlled diabetes compared to those with good glycaemic control. GV and GVSDS were inversely correlated to HbA1C (r = -0.356, P < 0.01 and r = 0.335, P < 0.01 respectively). GVSDS was correlated with serum IGF-I (r = 0.22, P < 0.01), FT4 (r = 0.321, P < 0.01) and inversely with basal GH (r = -0.362, P < 0.01) concentrations, but was not correlated with cortisol levels or peak GH concentrations in response to clonidine. GVSDS was correlated with HtSDS (r = 0.222, P < 0.01) and inversely with age (r = -0.43, P < 0.05). There was no significant correlation between GVSDS on the one hand and weight gain or body mass index (BMI) on the other hand. Peak GH response to clonidine was correlated with BMI (r = 0.68, P < 0.001) and insulin dose/kg/day (r = 0.602, P < 0.01). This study confirms that in children with IDDM linear growth velocity is dependent on the age of the child and the degree of glycaemic control, as well as on growth promoting hormones such as IGF-I and FT4. High BMI is associated with more GH secretion in response to clonidine, this might explain the higher requirements of insulin/kg in children with IDDM and high BMI.
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PMID:Growth parameters, growth hormone (GH) response to clonidine and circulating insulin-like growth factor-I (IGF-I), free thyroxine (FT4) and cortisol concentrations in relation to glycaemic control in children with insulin-dependent diabetes mellitus. 881 35

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease directed against the insulin-secreting beta cells of the islets of Langerhans of the pancreas. We have previously shown that in organ-specific autoimmune diseases, Graves' disease (GD), and IDDM, the antigen that is specific for each of these disorders (i.e., TSH receptor for GD, glutamic acid decarboxylase-65 (GAD65) for IDDM) does not activate the disease-specific CD8+ cells as fully as CD8+ cells from normal persons. In order to identify the specific antigen responsible for triggering or maintaining autoimmunity in patients afflicted with the disease, we have studied the effects of islet (beta) cell-specific antigens GAD65, insulin, pancreatic antigen (P69), T cell epitope 69 (Tep69), and a milk-derived bovine serum albumin (BSA)-peptide-ABBOS (pre-BSA positions 157-169) on the activation of CD8+ T lymphocytes in IDDM patients. We compared the patterns of T cells activation with those mediated by an irrelevant peptide antigen, P348 (amino-terminal region of human cardiac myosin light chain-1), and also tetanus toxoid. We also studied the responses of CD8+ T lymphocytes to these IDDM-relevant and -irrelevant antigens in Hashimoto's thyroiditis patients (HT), rheumatoid arthritis patients (RA), and normal control subjects (N) to compare the pattern of responses in the other autoimmune diseases. Activation of lymphocytes was monitored by measuring the expression of the activation molecule-major histocompatibility complex class II antigen (HLA-DR) on the surfaces of CD8+ T lymphocytes by flow cytometry. Peripheral blood mononuclear cells (PBMC) obtained from 14 patients with IDDM, 14 N, 14 with HT, and 13 with RA were cultured for 7 days in the presense or absence of antigens. The stimulation index (SI) of activation of the lymphocytes was determined. When the response of CD8+ T lymphocytes of IDDM patients to each of the IDDM-relevant antigens was compared to that of the irrelevant antigen, only GAD65 and ABBOS showed a significantly reduced activation compared to P348 and tetanus toxoid. Other relevant antigens, insulin, P69, and Tep69, did not show any significant differences in their SI compared to those of the irrelevant antigens. In the N, HT, and RA groups, there was no significant difference in the SI of the responses of CD8+ cells to any of the relevant antigens compared to that of the irrelevant antigens. Moreover, CD8+ T lymphocytes of IDDM patients showed a significantly lower activation by GAD65 than those from N, HT, and RA. In conclusion, our data suggest that CD8+ T lymphocytes of IDDM patients but not those from N, HT, and RA groups have specifically reduced potential for activation in response to GAD65 but not to insulin, P69, and Tep69, whereas ABBOS exerts a less well-defined reductive effect on the activation of CD8+ lymphocytes of IDDM patients. Since CD8+ cells have been shown to contain suppressor activity, our data support the notion that a disease-specific defect in GAD65 autoantigenic induction of suppressor T lymphocytes may be important in the pathogenesis of IDDM.
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PMID:Activation of CD8+ T lymphocytes in insulin-dependent diabetes mellitus. 907 47

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