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

The major histocompatibility complex (MHC) has long been associated with predisposition to several autoimmune diseases, including type 1 diabetes and autoimmune thyroiditis. In type 1 diabetes, a primary role has been assigned to class II genes, both in humans and in the nonobese diabetic (NOD) mouse model. However, an involvement of other tightly linked genes is strongly suspected. Here, through two independent sets of experiments, we provide solid evidence for the existence of at least one such gene. First, using a new recombinant congenic NOD strain, R114, we definitively individualized the Idd16 locus from the MHC in a 6-cM interval proximal to H2-K. It affords almost complete protection against diabetes and is associated with delayed insulitis. Second, by genome scan, we mapped non-H2 genes associated with the highly penetrant form of chronic experimental autoimmune thyroiditis (EAT) that is elicited in NOD and NOD.H2(k) mice by immunization with thyroglobulin. We identified one major dominant locus, Ceat1, on chromosome 17, overlapping with Idd16. Most importantly, R114 recombinant congenic mice challenged with thyroglobulin did not develop chronic EAT. This new major region defined by both Idd16 and Ceat1 might thus concur to the unique strength of the MHC in autoimmune susceptibility of NOD mice.
Diabetes 2002 Jul
PMID:An interval tightly linked to but distinct from the H2 complex controls both overt diabetes (Idd16) and chronic experimental autoimmune thyroiditis (Ceat1) in nonobese diabetic mice. 1208 44

The autoimmune polyendocrine syndrome type II (APS-II) is characterized by the association of autoimmune Addison's disease with thyroid autoimmune diseases or type-1 diabetes mellitus. 21-Hydroxylase autoantibodies enable the accurate diagnosis of autoimmune Addison's disease and, in patients with other endocrine autoimmune diseases, identify subjects at high risk for clinical adrenal insufficiency. 17 alpha-Hydroxylase (17OH) and side-chain-cleavage enzyme (P450scc) are target autoantigens of steroid-cell autoantibodies, and in women with Addison's disease, 17OH autoantibodies and P450scc autoantibodies are markers of increased risk for premature ovarian failure. Thyroperoxidase autoantibodies, thyroglobulin autoantibodies, H+/K(+)-ATPase autoantibodies, and GAD65 autoantibodies are frequently detected in patients with isolated Addison's or APS-II. Screening for other organ-specific autoimmune diseases should be performed in every patient with at least one major disease component of APS-II.
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PMID:Autoantibodies in autoimmune polyendocrine syndrome type II. 1209 56

High prevalence of goiter, other IDD such as impaired physical and intellectual growth and hearing deficit have been reported previously in Kiga. In order to evaluate the effect of iodized oil injection, this study was conducted in schoolchildren of Kiga village from 1989 to 1992. One ml of iodized oil solution containing 480 mg of iodine was injected into 198 schoolgirls and boys aged 8-14 years. Serum thyroid hormones, RT 3 U, TSH and thyroglobulin, before and 12, 24 and 36 months after the intra-muscular injection of iodized oil were measured. Assessment of urinary iodine was performed at the same periods by Foss method. Prior to the injection, all schoolchildren had goiters larger than grade 1 A (48% were grade 3); 3 years after intervention 20% had grades zero and 1 A and 8% grade 3 (P < 0.001). Urinary iodine was 11.4 +/- 19.8 before and increased to 113 +/- 63 and 83 +/- 66 microg/g creatinine 2 and 3 years after intervention. Mean serum T 4 was 5.0 +/- 2.1, 10.8 +/- 2.8, 9.8 +/- 2.5 and 9.5 +/- 2.1 microg/dl before and 12, 24 and 36 months after the injection, respectively (P < 0.001). Mean serum TSH was 20.3 +/- 22.8, 1.2 +/- 1.6, 0.8 +/- 1.2 and 2.2 +/- 0.9 mU/L in the same intervals, respectively (P < 0.001). Mean serum thyroglobulin was 132 +/- 107, 10 +/- 12 and 23 +/- 20 ng/ml before and at 2 and 3 years after injection, respectively (P < 0.001). Slight but significant increases in serum TSH and thyroglobulin occurred at 3 years after the injection. Findings show benefits of iodized oil administration in decreasing goiter size and in resuming normal thyroid function up to 3 years after the intervention. An increase in TSH and or thyroglobulin could be considered as the first sign of a fall in effectiveness of iodized oil injection.
Exp Clin Endocrinol Diabetes 2002 Nov
PMID:Three-year survey of effects of iodized oil injection in schoolchildren with iodine deficiency disorders. 1251 49

Latent autoimmune diabetes of adults (LADA) manifested after the age of 35 is characterized by the presence of disease-specific autoantibodies (anti-glutamate decarboxylase GADAb, anti-IA2Ab). However, autoimmunity in Type 1 diabetes mellitus is not targeted only to pancreatic beta-cells. No data have so far been published concerning the antibodies associated with other autoimmune disease in LADA patients. The presence of anti-thyroglobulin (TGAb), anti-thyroid peroxidase (TPOAb), anti-gliadin IgA (AGAAb) and IgG (AGGAb) and endomysial antibodies (EMAb) in sera of 68 diabetics typed as LADA was compared with the antibody presence in sera of 85 patients with Type 2 diabetes. We found a significantly higher occurrence of gliadin antibodies in LADA patients: the rate of AGGAb was 19.1% in comparison with 3.5% in the T2DM group (P = 0.0026), the rate of AGAAb was 13.2% in comparison with 3.5% (P = 0.035). The prevalence of EMAb was very low in both groups (1.5% and 0). The two groups differed significantly in the TPOAb rate: 22.1% in LADA compared to 9.4% in T2DM (P = 0.04), whereas no significant difference was found in the presence of TGAb (8.8% and 3.5%, P = 0.187). In comparison with T2DM patients, LADA patients were found to express higher antibody activity against gluten-related antigens and against TPO.
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PMID:Gliadin, endomysial and thyroid antibodies in patients with latent autoimmune diabetes of adults (LADA). 1282 88

The aim of our study was to evaluate antibodies against thyroglobulin (anti-TG) and thyroid peroxidase (anti-TPO) - markers of autoimmune thyroiditis - in several groups of adult patients with type 1 and type 2 diabetes mellitus (DM). We were particularly interested whether the presence of thyroid antibodies is related to the positivity of glutamic acid decarboxylase antibodies (anti-GAD). We found elevated anti-GAD in 46 % (97/210) patients with type 1 DM. All patients with type 2 diabetes were anti-GAD-negative. At least one thyroid antibody (anti-TG and/or anti-TPO) was found in 30 % (62/210) patients with type 1 DM and 27 % (22/83) type 2 diabetes patients. The patients with type 1 DM were further grouped according to their anti-GAD status. The anti-GAD-positive patients had a higher prevalence of anti-TG antibodies than the anti-GAD-negative patients (25 % vs. 12 %, p=0.03) as well as anti-TPO antibodies (32 % vs. 12 %, p<0.001). At least one thyroid antibody was detected in 39 % (38/97) of anti-GAD-positive but only in 21 % (24/113) of anti-GAD-negative patients with type 1 DM (p=0.006). No significant difference in the frequency of thyroid antibodies was found between anti-GAD-negative patients with type 1 and type 2 DM (21 % vs. 27 %, p=0.4). The groups with or without thyroid antibodies in both type 1 and type 2 diabetic patients did not differ in actual age, the age at diabetes onset, duration of diabetes, body mass index or HbA1c level. Patients with elevated thyroid antibodies had significantly higher levels of TSH than those without thyroid antibodies (1.86 vs. 3.22 mIU/l, p=0.04 in type 1 DM; 2.06 vs. 4.89 mIU/l, p=0.003 in type 2 DM). We conclude that there is a higher frequency of thyroid-specific antibodies in anti-GAD-positive adult patients with type 1 DM than in anti-GAD-negative patients or in patients with type 2 DM. Patients with or without thyroid antibodies do not differ in age, DM onset and duration, BMI or HbA1c. Thyroid antibodies-positive patients have higher levels of thyroid stimulating hormone (TSH).
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PMID:Anti-GAD-positive patients with type 1 diabetes mellitus have higher prevalence of autoimmune thyroiditis than anti-GAD-negative patients with type 1 and type 2 diabetes mellitus. 1520 35

Patients with type 1 diabetes mellitus (DM1) are at high risk to develop further autoimmune disorders, which are mostly characterized by the presence of organ-specific antibodies in serum and a subclinical disease course. Diabetes-related (glutamic acid decarboxylase, tyrosine phosphatase, IA-2) and thyroid-specific (thyroperoxidase, thyroglobulin) as well as antibodies to 20S proteasome, and anti-nuclear antibodies, were measured at DM1 onset in 147 children and adolescents. Patients were followed prospectively for the development of autoimmune thyroiditis (TSH elevation and/or sonographic thyroid gland enlargement in the presence of thyroid antibodies) up to 12 years, median observation time 4.4 years. Eight of 147 (5.4%) patients developed autoimmune thyroiditis. The cumulative incidence (+/-SE) at 5 years was 0.08+/-0.03. The prevalence of thyroid antibodies was 16.7%, of DM-related 88.4%, 20S proteasome 21.9%, and anti-nuclear antibodies 20.0%. There was a positive correlation between thyroid and anti-nuclear antibodies (p <0.001). Clinical course of DM1 and remission duration were not influenced by the presence of autoantibodies. However, in contrast to patients without antibodies, those with positive antibodies had significantly (p <0.001) elevated cumulative incidence of autoimmune thyroiditis at 5 years: thyroperoxidase 0.40+/-0.13, thyroglobulin 0.38+/-0.15, and anti-nuclear antibodies 0.29+/-0.12, respectively. These data underline that autoimmunity in patients with DM1 is not only restricted to beta-cell antigens at the onset of disease. In particular, patients with positive thyroid and anti-nuclear antibodies are at high risk to develop autoimmune thyroiditis during the first 5 years of DM1.
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PMID:Prevalence of 20S proteasome, anti-nuclear and thyroid antibodies in young patients at onset of type 1 diabetes mellitus and the risk of autoimmune thyroiditis. 1530 Oct 45

Inactivation of the autoimmune regulator (Aire) gene causes a rare recessive disorder, autoimmune polyendocrine syndrome 1 (APS1), but it is not known if Aire-dependent tolerance mechanisms are susceptible to the quantitative genetic changes thought to underlie more common autoimmune diseases. In mice with a targeted mutation, complete loss of Aire abolished expression of an insulin promoter transgene in thymic epithelium, but had no effect in pancreatic islets or the testes. Loss of one copy of Aire diminished thymic expression of the endogenous insulin gene and the transgene, resulting in a 300% increase in islet-reactive CD4 T cells escaping thymic deletion in T cell receptor transgenic mice, and dramatically increased progression to diabetes. Thymic deletion induced by antigen under control of the thyroglobulin promoter was abolished in Aire homozygotes and less efficient in heterozygotes, providing an explanation for thyroid autoimmunity in APS1. In contrast, Aire deficiency had no effect on thymic deletion to antigen controlled by a systemic H-2K promoter. The sensitivity of Aire-dependent thymic deletion to small reductions in function makes this pathway a prime candidate for more subtle autoimmune quantitative trait loci, and suggests that methods to increase Aire activity would be a potent strategy to lower the incidence of organ-specific autoimmunity.
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PMID:Gene dosage--limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity. 1549 24

In order to obtain prospective data on occurrence of thyroid autoantibodies [against thyroid peroxidase (antiTPO) and against thyroglobulin (antiTgl)] and their clinical relevance, we followed up on 109 young adults with Type 1 diabetes for 12 yr after diabetes onset. The patients were divided into subgroup I [positivity of both thyroid autoantibodies (T-Ab); 25%, women predominantly], subgroup II (isolated antiTPO positivity only, 26%, men and women equally) and subgroup III (thyroid autoimmunity not present, 49%, men mainly). Cumulative incidence of T-Ab during the 12 yr of follow-up was 51% with predominance of women over men (65% vs 38%, p<0.01). At the time of the first T-Ab detection, an ultrasonography pattern of a hypoechogenic thyroid gland was noted in 59% of subgroup I patients and in 25% of subgroup II patients (p<0.05). At the same time, TSH>4.5 mlU/I was shown in 30 and 7% of patients of subgroups I and II, respectively (p<0.05). In the patients with the repeated positivity of both T-Ab (subgroup I) subclinical hypothyroidism developed in all patients within 4 yr after the first detection of T-Ab. On the contrary, the clinical course in patients with isolated antiTPO positivity (subgroup II) was milder with 11% developing subclinical hypothyroidism within 4 yr after the first antiTPO detection (p<0.001). The data shed new light on the relative diagnostic value of thyroid antibodies, ultrasonography and functional examination for an early detection of thyroid autoimmunity of adult diabetic patients.
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PMID:Thyroid autoantibodies and their clinical relevance in young adults with type 1 diabetes during the first 12 yr after diabetes onset. 1563 24

A 81-year-old woman was diagnosed as having diabetes mellitus (DM) at 58 years of age. She started insulin therapy the following year, but her blood sugar levels were poorly controlled. At the age of 75, she tested positive for the anti-GAD antibody (7.8 U/ml) and was diagnosed as having slowly progressive type 1 DM (SPIDDM), as well as vitiligo vulgaris. At 78 years of age, chronic thyroiditis was diagnosed after positive tests for anti-thyroid peroxidase antibody and anti-thyroglobulin antibody. At the age of 81, general fatigue and jaundice appeared concomitantly with severe anemia, with Hb levels at 5.2 g/dl. Low serum vitamin B12 levels and the finding of erythroblastic hyperplasia with megaloblasts in bone marrow led to the diagnosis of pernicious anemia. Anemia was alleviated by intramuscular injections of vitamin B12. The patient developed chronic thyroiditis, vitiligo vulgaris, and pernicious anemia concomitantly with SPIDDM, and was diagnosed as having polyglandular autoimmune syndrome type III. Attention should be paid to these potentially associated autoimmune diseases in daily practice during the follow-up of SPIDDM patients.
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PMID:Slowly progressive type 1 diabetes mellitus associated with vitiligo vulgaris, chronic thyroiditis, and pernicious anemia. 1564 55

As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.
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PMID:Screening for associated autoimmunity in type 1 diabetes mellitus with respect to diabetes control. 1571 40


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