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)

Type I Diabetes mellitus (DM1) is the effect of T cell dependent autoimmune destruction of insulin producing beta cells in the pancreas islet. T cells are activated in response to islet dominant autoantigens, the result being the development of DM1. Insulin is one of the islet autoantigens responsible for activation of T lymphocyte functions, inflammatory cytokine production and development of DM1. The experiments reported in this study have shown the spontaneous increase of CD95 molecule expression on lymphocytes of the first-degree relatives of DM1 patients. The autoantigen insulin is responsible for stimulation in vitro of potentially hazardous 'memory' lymphocytes to produce interleukin-6 (IL-6) and interleukin-10 (IL-10) interleukins. Insulin induced stimulation of lymphocytes in vitro was observed in patients at high risk of developing diabetes mellitus (prediabetics). Phytohaemagglutinin (PHA) stimulates lymphocytes of all groups in the same way. Stimulated lymphocytes in second cultures undergo apoptosis induced with anti-Fas specific antibodies. The deletion in vitro of resting peripheral lymphocytes is nonfunctional. Insulin activated T lymphocytes, which undergo apoptosis were not observed in peripheral blood of healthy people and in patients with DM1. This observation suggests that insulin is involved as autoantigen in DM1 progression in patients with high risk of diabetes type I. The autoreactive T lymphocytes may persist in peripheral blood of patients with high risk DM1. Defective elimination of autoreactive T cells may result in autodestructive damage of islets beta cells in the prediabetic stage and disease progression to DM1.
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PMID:Activated T lymphocytes from patients with high risk of type I diabetes mellitus have different ability to produce interferon-gamma, interleukin-6 and interleukin-10 and undergo anti-CD95 induced apoptosis after insulin stimulation. 1116 80

The incidence of hypoglycaemic episodes in patients with type 1 diabetes mellitus (DM1) is frequent. They experience 1-2 symptomatic hypoglycaemias per week. 10-20% of the patients suffer from at least one severe hypoglycaemia per year. The incidence of severe hypoglycaemia in a group of intensely treated patients is about three times as high as compared with standard treatment and 55% of all episodes occur during sleep. Prevention of hypoglycaemia, and restoration of euglycaemia resp. include disappearance of metabolic effects of insulin and activation of glucose contraregulating systems among which there is a certain hierarchy. The phenomenon of unaware hypoglycaemia (FNH) is defined as failure to diagnose autonomous warning symptoms, and their non-appearance before the development of neuroglycopenia. The incidence of FNH in the population with DM1 is frequent. Based on a standardized insulin diffusion test 26% of patients with DM1 suffer from it which means that every fourth patient is affected. In the pathogenesis of FNH various factors and mechanisms were suggested as predisposing. Most probably a defect at the level of the central nervous system is involved caused by: 1. a reduced ability to recognize the decline of the blood sugar level by the CNS (altered function of the hypothalamic glucostat and/or glucose transport across the haematoencephalic barrier), 2. reduced secretion of neurotransmitters, 3. reduced tissue response to adequate neurotransmitter secretion. The theory of etiopathogenesis must explain and define its association with the persistence of diabetes mellitus, strict metabolic control, autonomous neuropathy and repeated episodes of hypopglycaemia. The contemporary hypothesis of the pathogenesis of FNH is the mechanism of repeated frequent hypoglycaemia which leads to general adaptative changes at the level of the CNS by increased glucose transport across the haematoencephalic barrier which leads to reduced hormonal responses and reduction of symptoms. Thus a dangerous circulus vitiosus is created where hypoglycaemia induces unawareness of hypoglycaemia. This condition is at least partly reversible. The presence of FNH should influence the decision of the physician before using an intensified insulin regimen in diabetics.
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PMID:[The phenomenon of unawareness of hypoglycemia]. 1139 72

The anthropometric status and metabolic control of 51 recently diagnosed Brazilian schoolchildren with type 1 diabetes (DM1), during the first 5 years of the disease, were compared with those of normal children (60 girls and 132 boys) belonging to the same environmental condition and pubertal stage. Metabolic control was evaluated on the basis of fasting plasma glucose (FPG) and HbA1c levels. The criteria of the National Center for Health Statistics were used for anthropometric evaluation. FPG (205 +/- 51 mg/dl for girls vs 200 +/- 34 mg/dl for boys) and % above upper normal limit of median HbA1c (1.8% for girls vs 2.5% for boys with diabetes) were not significantly different during follow-up. The Z-score of the last height evaluation was lower in the girls' group (-0.14 vs -0.53, P<0.05). By forward stepwise analysis, the Z-score of the initial height was statistically significant as a determinant factor for height at the end of the study in both girls and boys with DM1. The Z-score of weight at last evaluation was not different from that at diagnosis in either sex. However, analysis according to pubertal stage showed a tendency to a weight increase in the girls. The weight recovery and height loss in girls with DM1 follows the trend of the normal Brazilian population.
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PMID:Development according to pubertal stage in Brazilian children and adolescents with short-term diabetes. 1159 7

The purpose of this study was to examine psychomotor development in children born to mothers with type 1 diabetes mellitus (DM1) or gestational diabetes mellitus (GDM). The influence of metabolic control in pregnant diabetic mothers and complications during labor on their children's psychological and physical development was evaluated. The analysis included 59 children, 20 of mothers with GDM, 19 of mothers with DM1, and 20 children of healthy mothers. Clinical observations and medical history were recorded and children were assessed using the Brunet-Lezine Psychomotor Development Scale. Abnormalities were found more often in the children of mothers with DM1 whose illness was insufficiently controlled during pregnancy and of mothers with serious hypoglycemia while pregnant. Speech, eye-movement coordination and social aspects were affected.
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PMID:Psychomotor development in the children of mothers with type 1 diabetes mellitus or gestational diabetes mellitus. 1192 29

Antibodies to glutamic acid decarboxilase (GAD-Abs) are present in the serum of 60-80% of newly diagnosed type 1 diabetes (DM1) patients and patients with autoimmune polyendocrine syndrome (APS) associated with DM1. Higher titre of GAD-Abs are also present in the serum of 60% of patients with stiff-man syndrome (SMS) and all reported patients with cerebellar ataxia associated with polyendocrine autoimmunity (CAPA). Several studies suggest that GAD-Abs may play a critical role in the pathogenesis of SMS and CAPA but little is known about T-cell responsiveness to GAD-65 in these neurological diseases. To analyse cell-mediated responses to GAD, we studied the peripheral blood lymphocyte proliferation and cytokine responses to recombinant human GAD-65 in 5 patients with SMS, 6 with CAPA, 9 with DM1, 8 with APS and 15 control subjects. GAD-65-specific cellular proliferation was significantly higher in SMS than in CAPA, DM1, APS or controls. In contrast, only T cells from CAPA patients showed a significantly high production of interferon-gamma after GAD stimulation, compared to all other patients and controls. No differences were found for IL-4 production. These results suggest that, despite similar humoral autoreactivity, cellular responses to GAD are different between SMS and CAPA, with a greater inflammatory response in CAPA, and this difference may be relevant to the pathogenesis of these diseases.
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PMID:T-cell reactivity to glutamic acid decarboxylase in stiff-man syndrome and cerebellar ataxia associated with polyendocrine autoimmunity. 1219 88

The contribution of HLA genes to the genetic risk for celiac disease (CD) has been known for a long time. Recent publications have pointed to the possibility that a second, independent susceptibility locus could be located in the same genomic region, and a triplet repeat polymorphism in exon 5 of the gene MHC class I chain-related protein A (MICA; located between TNFA and HLA-B) has been associated with several autoimmune disorders, including type 1 diabetes mellitus (DM1) and Addison's disease. On the other hand, a single amino acid change in exon 3 of MICA (M129V) has been shown to strongly reduce MICA binding to NKG2D, an activating natural killer receptor expressed also on T cells, and this could have significant effects on autoimmune reactions. In this study, we have analyzed the contribution of these polymorphisms to CD in 37 Basque families, and have constructed MICA-HLA-DRB1 haplotypes to determine whether MICA has an effect independent from the HLA class II conferred risk. In our population, HLA-DRB1*0301 was associated with an increased risk for CD, while HLA-DRB1*1501 conferred protection from the disease (OR: 7.38 and 0.06, respectively). On the other hand, MICA allele A4 was positively associated with the disease (OR: 4.69) whereas allele A9 showed a trend towards protection (OR: 0.18), although significance did not hold after correction. No association of the exon 3 biallelic polymorphism was observed. A positive allelic association was found for haplotypes A5.1-DRB1*0301 (associated with risk for disease), A4-DRB1*0301 and A6-DRB1*07. In view of our results, both HLA-DRB1 and MICA are associated with CD, but stratification analysis did not show any independent contribution of the MICA polymorphisms analyzed to CD risk. Besides, MICA allele A4 (also A5.1 was associated with risk for CD and other diseases) is in strong linkage disequilibrium with HLA-DRB1*0301. Finally, the major histocompatibility complex region's conferred susceptibility to CD, at least in Basque, is very similar to that observed for DM1, with shared risk and protective haplotypes.
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PMID:HLA-DRB1 and MHC class 1 chain-related A haplotypes in Basque families with celiac disease. 1236 85

The HLA complex, located on the short arm of chromosome 6, is the strongest genetic marker for type 1 diabetes (T1DM). In previous study we demonstrated association between genes HLA-DRB1 and HLA-DQB1 and T1DM in the Polish population. There is a strong-independent association of alleles HLA-DRB1*0401 and DQB1*302, despite population linkage disequilibrium among alleles of these genes. The aim of the current study was to verify a hypothesis that some alleles or haplotypes of HLA-DRB1, DQA1 and DQB1 genes increase the risk for familiar aggregation of T1DM. We analysed 507 patients with IDDM derived from 80 multiplex and 325 patients from simplex families. PCR and hybridisation with SSO probes performed HLA typing for DRB1, DQA1 and DQB1 alleles. Genetic analysis demonstrated strong association of allele HLA-DQB1*0302 with T1DM in the Polish population in families with single (DM1) and more numerous cases (DM2) cases, compared with healthy cases (n=103). The HLA-DQB1*302 allele frequencies were 27.8% vs 8.7%; Pc<10(-5); OR(95%CI)=4,03(3.80-4.25) and 16.3% vs 8.7%; Pc<0.04; OR(95%CI)=2.04(1.79-2.89), respectively. The presence of allele HLA-DQB1*0602 has a strong protective effect from T1DM in both studied groups (1.46% vs. 13.6%; Pc<10(-5); OR(95%CI)=0.09(-0.25-0.44) and 0.98% vs. 13.6%; Pc<10(-5); OR(95%CI)=0.06(-0.46-0.58), respectively. Interestingly, HLA-DRB1*04 allele more often co-segregated with DM2 families as comparing the DM1 group (31.0% vs. 15.8%, respectively; Pc<10(-5)). However in both cases differences remain significant as compared to controls: Pc<10(-5), OR (95%CI)=3.52(3.33-3.70) and Pc<10(-5) OR(95%CI)=6.17(5.97-6.37), for DM1 and DM2 respectively. Subtyping of HLA-DRB1*04 alleles demonstrated that the strongest predisposing effect has been identified with DRB1*0401. Moreover, difference in frequencies of the protective allele HLA-DQB1*0301 among DM1 and DM2 group was revealed (8.8% vs. 13.7%, respectively; Pc<10(-5)) and the protective effect of this allele remained only significant in DM1 group: 8.8% vs. 19.9%; Pc<10(-5); OR(95%CI)=0.39(0.19-0.58). The results suggest that it is likely that familial aggregation of T1DM is associated with lower frequency of protective alleles of HLA-DQB1 gene.
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PMID:[Alleles of HLA-DQB1 and familial aggregation of type 1 diabetes]. 1287 86

The effect of a number of host and environmental factors on the onset of type 1 diabetes mellitus (DM1) in a group of Lebanese children and young adults was studied. Results showed that DM1 in a group of 253 patients presented no gender preference and that the age of onset was similar in both genders. The overall body mass index reflected good metabolic control. HbA1c had a mean value of 8.98%, suggesting poor glucose control. Family history of DM1 and type 2 diabetes mellitus as well as consanguinity in patients' families were not different from those reported in the literature. Finally, onset of DM1 showed seasonal variation, peaking during winter months. DM1 showed a higher prevalence of onset among children born first and a decreased incidence as birth order increased. This study provides valuable data for the diagnosis, control and prevention of DM1 in children.
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PMID:Host and environmental factors defining the epidemiology of type 1 diabetes mellitus in a group of Lebanese children and young adults. 1288 Jan 26

The aim was to study the monthly rhythm of birth and clinical onset in 303 children with type 1 diabetes mellitus (DM1) aged 0-15 years (156 males, 147 females) born between 1980 and 1996 in Ireland and compare to 951,717 infants born in the general population during the same period. Analysis was performed using the cosine fit for rhythm and t-test between the seasons of the year. Whereas the males showed a rhythmic pattern of month of birth, peaking in the summer (p < 0.05), similar to that in the general population, the females showed no seasonal differences in either month of birth or month of onset. A mirror image pattern, nadir in spring and summer (p < 0.01), was observed in month of clinical onset, also only in males. If we assume a viral infectious etiology of DMI, females seem to be less susceptible than males to the environmental infectious influences.
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PMID:Differences between males and females in the seasonality of birth and month of clinical onset of disease in children with type 1 diabetes mellitus in Ireland. 1250 65

The aim of this cross-sectional study was to assess and compare thyroid volume and its derminants in a cohort of type 1 diabetes mellitus (DM1) and compare the results to a healthy control group. We studied 65 DM1 patients treated with an intensive insulin regimen and 65 matched controls. In all participants we evaluated weight, height, BMI, waist-hip ratio, body surface area and body composition variables determined by using a bioelectrical impedance analyser. Thyroid size was estimated by ultrasonography. We determined basal TSH, anti-thyroid antibodies and urinary iodine excretion. Body weight, height, BMI and body surface area were similar in DM1 patients and in controls. Fat-free mass was higher in both male and female DM1 patients than in controls (64.4 +/- 6.9 vs. 60.4 +/- 8.2 kg, p=0.03 and 48.3 +/- 5.7 vs. 45.4 +/- 6, p=0.04, respectively), and fat mass was lower in male DM1 patients than in controls (9.7 +/- 7 vs. 14.2 +/- 8.1 kg, p=0.01). Thyroid volume was greater in both male and female DM1 patients than in controls (11.12 +/- 2.87 vs. 9.63 +/- 2.27 ml, p=0.0001 and 9.5 +/- 2.3 vs. 7.7 +/- 2 ml, p=0.002, respectively). Urinary iodine excretion was similar in the two groups. In both DM1 patients and controls, thyroid volume correlated with weight, height, BMI, waist-hip ratio, body surface area, fat-free mass and the multivariate linear regression analysis with thyroid volume as the dependent variable showed that fat-free mass in either group was the only significant determinant of thyroid volume. We conclude that DM1 patients had larger thyroid volume compared with healthy controls with similar anthropometry; body composition is different in DM1 patients and that the anthropometric and body composition variables, especially fat-free mass and body surface area, predict thyroid volume either in DM1 patients or in healthy controls.
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PMID:Thyroid volume as measured by ultrasonography in patients With type 1 diabetes mellitus without thyroid dysfunction. 1295 66

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