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

The status of various vitamins and trace metals in plasma of 100 Non Insulin Dependent Diabetes Mellitus subjects was compared to those of 112 age and sex matched healthy subjects. The plasma concentration of riboflavin, pyridoxine and folic acid were found to be decreased in the diabetic patients while retinol and ascorbic acid were relatively increased, in comparison to the healthy subjects. However in the Non Insulin Dependent Diabetes Mellitus subjects the mean plasma concentration of all the metals and vitamins except for riboflavin were within the range of normal values. In spite of these findings, the percent of diabetic patients with various vitamin or metal deficiencies, e.g. riboflavin, carotene, thiamin, retinol, zinc and iron were significantly higher than those in the healthy population. We conclude that vitamin and metal deficiency is common in Non Insulin Dependent Diabetes Mellitus subjects.
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PMID:Vitamins and trace metals status in non insulin dependent diabetes mellitus. 180 38

Neonatal polycythemia is a perinatal complication in infants of diabetic mothers. The cord CBC (complete blood counts), serum iron, transferrin and ferritin concentrations were studied in newborn infants of 9 GDM (gestational diabetes), 21 NIDDM (noninsulin-dependent diabetes mellitus), and 8 IDDM (insulin-dependent diabetes mellitus) mothers. The RBC (red blood cell) count, Hb (hemoglobin) and Hct (hematocrit) of these infants were higher than control infants. There was no difference between the serum iron concentration of the infants of each group diabetic mothers and the infants in the control group, but the transferrin concentration was significantly higher and the ferritin was significantly lower in the infants of diabetic mothers than in those of control mothers. There was a significant negative correlation between transferrin and ferritin (r = -0.491 p less than 0.001). Erythropoiesis is considered to be enhanced in the fetuses of diabetic mothers, and the iron needed for erythropoiesis is reportedly transported from the mother to the fetus according to the demands of the fetus, but the iron storage was shown to be reduced in the fetuses of diabetic mothers.
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PMID:Cord transferrin and ferritin values for erythropoiesis in newborn infants of diabetic mothers. 263 11

BB rats were found to have autoantibodies to gastric parietal cells, thyroid colloid antigens, smooth muscle, and thymocytes. No autoantibodies reactive with pancreatic islet cells (cytoplasmic), thyroid epithelial cells, adrenal cortex, testes, or anterior pituitary sections were identified. BB rats with gastric parietal autoantibodies had modest degrees of lymphocytic gastritis, but none developed iron or vitamin B12 deficiencies. These results suggest that BB rats have an underlying autoimmune diathesis. In addition, reports of peripheral T lymphopenia in such rats were confirmed, and markedly reduced helper T cell and cytotoxic-suppressor T cell subsets were demonstrated. Histological studies also revealed depletions of the T cell areas of spleen and lymph nodes. Furthermore, BB rats exhibited a profound inability to reject skin grafts across major and minor histocompatibility barriers. This was confirmed by mixed lymphocyte culture studies in vitro. BB-rat lymphocytes from either spleen or peripheral blood also showed profoundly reduced responses to T cell mitogens. Although BB-rat lymphocytes could produce normal levels of interleukin-2, they were unable to respond to this T cell growth factor. However, examination of thymuses from BB rats showed largely normal histologies, normal numbers of thymocyte subsets, and good mitogenic responses to con A. Thus, it appears that BB rats may have a thymic or post thymic defect in T lymphocyte maturation. The relevance of the immunologic lesion to the etiology of IDD in BB rats remains to be shown.
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PMID:Autoimmune diatheses and T lymphocyte immunoincompetences in BB rats. 634 99

Hydroxyl radicals (.OH) may contribute to beta cell death. Because iron catalyzes .OH production, we examined whether administration of a novel, long-acting iron chelator, hydroxyethyl starch-deferoxamine (HES-DFO) could prevent diabetes in spontaneously diabetic biobreeding (BB) rats. In our colony, a peripheral lymphocyte count (PBLC) < 4200 mm3 has an 88% positive predictive value for onset of diabetes mellitus (DM). Rats with PBLC < 4200 mm3 were randomized at 6 weeks of age to receive 50 mg/kg of HES-DFO (a high molecular weight hydroxyethyl starch-conjugated derivative of deferoxamine) or equimolar hydroxyethyl starch (HES) alone given intraperitoneally three times weekly until DM or 120 days of age. Administration of HES significantly decreased the incidence of IDDM to 57% as compared with the incidence of 87% in the lymphopenic unmanipulated BB rats in the colony (p < 0.01). Administration of HES-DFO further significantly decreased the incidence of IDDM to 31% as compared with the lymphopenic unmanipulated rats (p < 0.01). When analyzed by sex, 3 of 17 (18%) HES-DFO-treated males developed DM, versus 10 of 17 (58%) of HES-treated males (p < 0.05, chi square); 8 of 19 (42%) of HES-DFO-treated females developed DM, versus 11 of 20 (55%) HES-treated females (p = NS). There were no differences between the groups in (1) mean time of onset of DM, (2) serum iron levels at study entry and completion, (3) weekly hematocrits, (4) total lymphocyte counts; and (5) weekly weight gains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydroxyethyl starch deferoxamine, a novel iron chelator, delays diabetes in BB rats. 751 76

Insulin-dependent diabetes mellitus (IDDM) is a frequent complication in patients with beta-thalassaemia major. It is believed to be a consequence of the damage inflicted by iron overload to the pancreatic beta-cell. Liver disorders and genetic influences seem to be additional predisposing factors to diabetes mellitus in patients with beta-thalassaemia. Ethnic variations are frequently reported on prevalence and complications of diabetes mellitus in the beta-thalassaemia patients. We investigated 50 Saudi children (< 15 years) with beta-thalassaemia major and 50 beta-thalassaemia minor, and age- and sex-matched controls for the prevalence of diabetes mellitus, and its relation to hitherto claimed predisposing factors. Fasting blood glucose, plasma insulin level, liver function tests, plasma ferritin, iron, and transferrin were assessed in each patient and glucose tolerance was evaluated. Results in patients with beta-thalassaemia major were compared with those obtained for beta-thalassaemia minor and the controls. The results showed moderate elevation of ferritin level in the majority of the beta-thalassaemia major despite desferroxamine therapy. Either hyperinsulinaemia or hypoinsulinaemia was encountered in the majority of these patients. The prevalence of diabetes mellitus was 6 per cent compared to 2 per cent in the beta-thalassaemia minor and normal children. Impaired glucose tolerance (IGT) occurred at a significantly higher (24 per cent) frequency in the beta-thalassaemia major compared to 2 and 0 per cent in the beta-thalassaemia minor patients and normal controls, respectively. The prevalence of diabetes mellitus was significantly lower in the Saudi thalassaemic patients compared to the results obtained from patients of other ethnic groups reported in literature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diabetes mellitus in children suffering from beta-thalassaemia. 780 19

In the search for diabetes genes, the combined approaches of positional cloning with random markers and subsequent evaluation of candidate genes mapping to areas of interest will be increasingly used. For islet candidate genes of unknown function, expressed trinucleotide (triplet) repeats represent a unique subset. It is unlikely that abnormal expansion of expressed islet triplet repeats would be a major cause of diabetes, yet the triplet repeats are frequently polymorphic and can thus be used to map the genes in the human genome. In this study, a human islet cDNA library was screened with (CGG)7 and (CAG)7, and 23 triplet repeats were isolated. Sequencing revealed four known and six novel islet genes containing 4-15 triplet repeats. The four known cDNAs included ferritin, the major iron-binding protein in cells; HSGSA2R, a full-length clone of the alpha-subunit of the G-regulatory protein; HUMSATB1A, a DNA-binding protein expressed predominantly in thymus; and HUMPPA-PRO, a ribosomal protein. The triplet repeats in ferritin and HUMPPAPRO were found to be monomorphic. Characterization of the six unique novel expressed islet triplet cDNAs revealed that they were 0.6-1.5 kb in size, contained 4-15 triplet repeats, and were expressed in islets and all other tissues examined. Four of the novel clones, CGG-isl 10, CGG-isl 11, CAG-isl 6, and CAG-isl 7, were mapped to human chromosomes 19, 16, 12, and 3, respectively, via somatic cell hybrids. One islet cDNA, CAG-isl 7, contained a repeat that was highly polymorphic, with 14 alleles (4-18 triplets) in African-Americans (heterozygosity = 0.86) and 6 alleles (heterozygosity = 0.77) in whites. Northern analysis indicated that the mRNA was abundant in pancreatic islets. A putative full-length clone contained an open reading frame encoding 213 amino acids with a variable number of alanines (4-18) within the COOH-terminal. The gene was uniquely mapped with odds > 1,000:1 on chromosome 3p in Centre d'Etude du Polymorphisme Humain pedigrees. There were no differences in CAG-isl 7 allele frequencies between African-American patients with NIDDM (n = 108) and control subjects (n = 116), nor was expansion above 18 repeats noted. Linkage analysis in 14 nonglucokinase maturity-onset diabetes of the young pedigrees showed a cumulative logarithm of odds score of -33.19 at theta = 0.00. Abnormal expansion was not observed in 20 IDDM patients with one NIDDM parent. While these data suggest no major role for CAG-isl 7 in diabetes, at least four of the six novel islet triplet genes are coexpressed in pancreatic islets and neural tissue, and these genes can now be considered as candidates for diabetes and/or neuropsychiatric diseases.
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PMID:Identification of trinucleotide repeat-containing genes in human pancreatic islets. 854 59

In vitro, cytokines like interleukin-1-beta (IL-1-B) and tumour necrosis factor-alpha (TNF-A) inhibit insulin release and can destroy islet B-cells. We measured blood levels of IL-1-B, TNF-A, and islet cell antibody (ICA) in 20 children with IDDM, 20 of their non-diabetic siblings, 20 children with thalassemia major on long-term hypertransfusion therapy and iron chelation, and 10 normal age-matched children. In the non-diabetic and thalassemic children we investigated the early phase of insulin release after i.v. glucose (0.5 g/kg, 30 per cent solution) and evaluated tolerance to oral glucose (1.75 g/ kg). Circulating IL-1-B and TNF-A concentrations were significantly higher in IDDM-siblings (33.7 +/- 12.7 pg/ml and 655 +/- 165 pg/ml, respectively) v. normal children (21.1 +/- 6.4 pg/ml and 383 +/- 122 pg/ml, respectively). Thalassemic children had no detectable circulating ICA. The prevalence of ICA was 30 per cent in children with IDDM and 60 per cent of their siblings. Impaired oral glucose tolerance was detected in five children with thalassemia (25 per cent), but in none of the IDDM-siblings. The early phase of insulin release was significantly depressed in thalassemic children (peak insulin = 29.2 +/- 5.1 mIU/ml) v. normal children (52.3 +/- 9.5 mIU/ml) and IDDM-siblings (45.3 +/- 12.4 mIU/ml). It appears that thalassemic children had significantly decreased insulin secretion and impaired glucose tolerance, however, the mechanism of B-cell dysfunction is not mediated by ICA nor by cytokines.
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PMID:Interleukin-1-beta, tumour necrosis factor-alpha, islet-cell antibody, and insulin secretion in children with thalassemia major on long-term blood transfusion. 900 65

When cultured NIT-1 cells were subjected to a low level of oxidative stress (30 microM hydrogen peroxide for 15 min at 37 degrees C) several of their lysosomes ruptured, as demonstrated by intravital staining with the lysosomotropic weak base acridine orange. Such rupture is due to intralysosomal, iron-catalyzed oxidative reactions, since it was largely prevented by previous endocytotic uptake of desferrioxamine. The resultant limited leakage of lysosomal hydrolytic enzymes into the cytosol could be important for an apoptotic-type degradation/fragmentation process within initially intact plasma membranes. In contrast, extensive lysosomal rupture leads to necrosis. The development of the damage process was followed by light- and electron microscopy; and by the TUNEL-reaction. As a result of the applied oxidative stress, which is comparable to that expected to occur within the microenvironment surrounding activated macrophages under oxidative burst (e.g. during autoimmune insulitis), about 90% of the cells eventually died due to post-apoptotic secondary necrosis. The few surviving cells phagocytosed the debris from their fragmented neighbours and began to divide about 24 h after the insult. Thus the sensitivity to oxidative stress varies, perhaps as a consequence of varying amounts of intralysosomal redox-active iron, as we have found to be the case in several other cellular systems. Since the NIT-1 cells are highly differentiated, and in many ways like beta cells, we consider our result to be of value for the understanding of beta-cell death during the development of insulin-dependent (Type I) diabetes mellitus (IDDM).
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PMID:Minute oxidative stress is sufficient to induce apoptotic death of NIT-1 insulinoma cells. 1051 25

The Middle East is perhaps the world's best laboratory for learning more about iron and zinc deficiencies, and their widespread prevalence contributes much to constraining the quality of life for a large share of the population. Always, in the context of endemic IDD, countries in the region need to make sure that the programs are in place to consign this still-serious problem to the history books. Research is not required so much in relation to IDD, but clearly applications need to be monitored. Vitamin A deficiency is probably widespread at mild to moderate levels, and should be addressed by a combination of appropriate case management for infectious disease, breastfeeding promotion, and dietary diversification/nutrition education. Iron deficiency is the most prevalent, and so far the most intractable, micronutrient problem. It probably will not yield to less than a multipronged strategy including fortification of the food supply with iron. Several other micronutrient deficiencies require our eventual attention as well, and looking forward to their solution should be part of the research agenda.
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PMID:Micronutrient deficiency conditions in the Middle East region: an overview. 1141 Dec 62

The generation of an autoimmune response against islet beta-cells is central to the pathogenesis of type 1 diabetes mellitus, and this response is driven by the stimulation of autoreactive lymphocytes by components of the beta-cells themselves. Reactive oxygen species (ROS) have been implicated in the beta-cell destruction which leads to type 1 diabetes and may modify beta-cell components so as to enhance their immunogenicity. We investigated the effects of oxidation reactions catalysed by copper or iron on the major beta-cell autoantigen glutamic acid decarboxylase (GAD). Lysates of purified rat islets were exposed to copper or iron sulphate with or without hydrogen peroxide or ascorbic acid. Immunostaining showed that these treatments generated high molecular weight covalently linked aggregates containing GAD. These are not formed by intermolecular disulphide bonds between cysteine residues since they cannot be resolved into monomeric form when electrophoresed under extreme reducing conditions. There was no modification of insulin or pro-insulin by ROS. The same oxidative changes to GAD could be induced in viable islet cells treated with copper sulphate and hydrogen peroxide, and thus the modifications are not an artefact of the catalysed oxidation of cell-free lysates. Sera from patients with type 1 diabetes and stiffman syndrome containing GAD antibodies reacted predominantly with the highest molecular weight modified protein band of GAD: normal human sera did not precipitate GAD. Thus, oxidatively modified aggregates of GAD react with serum antibodies of type 1 diabetes patients and some SMS patients: this is consistent with oxidative modifications of autoantigens being relevant to the pathogenesis of type 1 diabetes.
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PMID:Islet glutamic acid decarboxylase modified by reactive oxygen species is recognized by antibodies from patients with type 1 diabetes mellitus. 1170 67


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