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

Hemochromatosis is a syndrome which, when fully expressed, is manifested by melanoderma , diabetes mellitus, and liver cirrhosis, with iron overload involving parenchymal and reticuloendothelial cells in many organ systems. This clinical presentation may arise as a consequence of either hereditary or acquired abnormalities of iron overload, although the mechanisms are quite different. In hereditary hemochromatosis (also known as primary, or idiopathic, hemochromatosis), increased intestinal iron absorption leads to excessive accumulations of iron, throughout the body, particularly in parenchymal cells. In secondary forms of iron overload including transfusional hemosiderosis, alcoholic cirrhosis, thalassemia, sideroblastic anemia, and porphyria cutanea tarda, iron accumulates in the reticuloendothelial system initially, but with increasing amounts of total body iron, excessive iron deposits eventually accumulate in parenchymal cells throughout the body producing a picture indistinguishable from hereditary hemochromatosis. In this article, the course, prognosis, and therapy of iron overload will be reviewed in detail. Clinical and experimental data concerning the pathogenesis of the different forms of iron overload will be examined critically. In particular, information relating to possible abnormalities of reticuloendothelial function, intestinal mucosal iron transport, and alterations in serum and tissue isoferritin patterns in hereditary hemochromatosis will be analyzed, and possible directions for future research will be suggested. The mode of inheritance and linkage with the major histocompatibility (HLA) complex will be discussed. Theories on the pathogenesis of tissue damage by excess iron will be evaluated. Methods for measuring the extent of iron overload in clinical practice will be described, including measurements of serum iron, serum ferritin, iron absorption, cobalt excretion, desferrioxamine excretion, liver biopsy and tissue iron determinations, and HLA typing. Finally, unresolved problems in the understanding of the disease process, diagnosis, and therapy will be delineated.
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PMID:Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy. 637 41

3 cases of congenital dyserythropoietic anaemia (type I, case 3; type III, cases 1 and 2) are reported with a follow-up of 8-10 years. Conventional therapy with vitamins, steroids and/or anabolic hormones was ineffective. Regular blood transfusions were required to maintain the haemoglobin levels around 8 g/dl. Splenectomy, however, resulted in a sustained rise in haemoglobin without blood transfusions. During the follow-up period varying from 40 to 77 months after splenectomy, diabetes mellitus was detected in all 3 patients. Liver biopsy showed haemosiderosis in 2 patients with cirrhosis in one of them. It is suggested that splenectomy could be an effective mode of therapy to reduce the need for blood transfusion in congenital dyserythropoietic anaemias.
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PMID:Congenital dyserythropoietic anaemias: splenectomy as a mode of therapy. 679 78

33 patients with chronic renal failure were divided into two groups. Group I consisted of 8 non-dialysed patients without any clinical or biochemical sign of liver disturbance nor any iron supplementation. Group II consisted of 25 maintenance hemodialysis (MHD) patients treated from 2 to 13 years. 19 subjects had chronic B hepatitis. Total exogenous iron load parenteral iron and/or blood transfusions) was calculated. Body iron overload (hemosiderosis) was assessed by liver iron concentration (LIC) in needle biopsy specimens according to Barry's method (less than 200 microgram/100 mg dry weight) and serum ferritin levels (less than 360 ng/ml). 4 patients whose serum ferritin was increased with or without hepatic fibrosis and with or without any organ dysfunction due to hemochromatosis received i.v. infusions of desferrioxamine in doses of 2 g at each dialysis. Serum ferritin levels were correlated with LIC (p less than 0.001) and iron load (p less than 0.001). Hemosiderosis was noted in 16 MHD patients (group II) and correlated with iron load. Hemochromatosis was noted in 4 patients (group II). 4 hemodialysed patients with iron overload were treated by desferrioxamine from 6 to 18 months. During this therapy, body iron stores fell and organ dysfunction (heart failure, hepatic cytolysis, anaemia, diabetes mellitus improved. Long-term chelation therapy by desferrioxamine was effective and the chelated iron was readily removed by dialysis. These data show the importance of precise evaluation of iron stores in MHD patients.
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PMID:[Iron-overload in patients on maintenance hemodialysis: diagnostic criteria, indications and treatment by desferrioxamine (author's transl)]. 732 1

We identified a mutation in the ceruloplasmin (Cp) gene in a Japanese family with aceruloplasminemia, some of whose members showed extrapyramidal disorders, cerebellar ataxia, and diabetes mellitus. A post-mortem study of the proband revealed excessive iron deposition mainly in the brain, liver and pancreas. The G to A transition at the splice acceptor site introduces a premature termination codon at the amino acid position 991 by defective splicing, thereby truncating the carboxyl terminus of Cp in affected individuals. We conclude that the mutation in the Cp gene is associated with systemic hemosiderosis in humans.
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PMID:A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. 753 72

A 54 year-old previously healthy woman was admitted with staphylococcus aureus septicaemia. The patient had been treated with oral iron supplementation for two years due to fatigue. In the evaluation of postinfectious anaemia, serum transferrin saturation and serum ferritin were found persistently elevated with values of 74% and 950 micrograms/1, respectively. Hereditary haemochromatosis was suspected even though there was no history of liver disease or diabetes mellitus in the family. A bone marrow biopsy showed a normal content of haemosiderin iron. The liver biopsy revealed haemosiderosis, mainly located to the periportal hepatocytes, and fibrosis in the portal tracts. The HLA-type was A3, B7, B37. Over a period of ten months, a total of 3.9 g of iron was removed by venesection while S-ferritin declined to 31 micrograms/l. A sister to the proband had an identical HLA type, but normal iron status markers, either indicating heterozygosity or homozygosity with lack of penetrance. In preclinical hereditary haemochromatosis, early diagnosis and treatment is essential in order to prevent organ damage and to improve prognosis. Prophylactic screening is recommended. The identification of one homozygous subject in a Danish year-cohort of 60.000 persons costs approximately 40.000 Danish kroner (7.000 US+).
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PMID:[Preclinical hereditary hemochromatosis--is there an indication for preventive screening?]. 765 9

A long-term investigation of bone mineral metabolism in a newly developed strain, the WBN/Kob rat, which spontaneously develops diabetes, possibly due in part to hemosiderin deposition, was conducted. WBN/Kob rats used in this study developed diabetes after 9 months of age. Bone mass peaked at 6 months or 8 months of age, and femoral breaking strength was maximal at 8 months of age, declining rapidly after the development of diabetes. In contrast, both the bone mass and the mechanical strength increased up to 14 months of age in controls. The serum osteocalcin (BGP) levels were lower at 4 months of age and serum 1.25(OH)2D levels were significantly lower throughout the study in WBN/Kob rats than in controls. These results suggest that abnormal bone and mineral metabolism is present in WBN/Kob rats before the onset of diabetes, and that bone strength and BMD decrease simultaneously with the development of diabetes. This strain can serve as a useful model, not only of hemosiderosis and diabetes, but also of osteopenia.
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PMID:WBN/Kob rat: a new model of spontaneous diabetes, osteopenia and systemic hemosiderin deposition. 771 21

Life expectancy of patients suffering from homozygous beta-thalassaemia has been improved due to the modern treatment of this disease. This has allowed development of late hemosiderosis-related complications and disturbances of the endocrine and exocrine functions of the pancreas. Carbohydrate metabolism of 16 patients with thalassaemia major was studied. Three of them presented with a pronounced clinical picture and biochemical constellations of a severe diabetes mellitus. The remainder had no clinical symptoms of carbohydrate metabolism disorders. The pancreatic beta-cell function of the patients was assessed by measuring the serum concentrations of immunoreactive insulin and by a glucose tolerance test. Most patients showed very low basal insulin levels while glucose tolerance was reduced in only one of them. In this patient we also established delayed insulin response after an intravenous glucose load. We concluded that the disturbed insulin secretion found in the children studied is most likely the earliest manifestation of the pancreatic beta-cell insufficiency which precedes the changes in the glucose tolerance.
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PMID:Secondary diabetes in children with thalassaemia major (homozygous thalassaemia). 786 89

Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a new disease characterized by systemic hemosiderosis, diabetes mellitus, neurological abnormalities and pigment degeneration of the retina. Loss of the ferroxidase activity of ceruloplasmin results in systemic iron deposition and tissue damage. Neuroimaging studies reveal iron deposition in basal ganglia and in the red and dentate nuclei. Cerebellar ataxia, extrapyramidal signs and dementia develop after middle age. We report a patient with undetectable serum ceruloplasmin levels and the above clinical manifestations. Sequence analysis of the cDNA of ceruloplasmin from this patient revealed an insertion of adenine in exon 3; this produced a premature stop codon.
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PMID:Hereditary ceruloplasmin deficiency with hemosiderosis. 864 92

Administration of vitamins or metals may cause severe side effects. Retinoids (derivatives of vitamin A) used for the treatment of various skin disorders are teratogenic, hepatotoxic and may induce a substantial increase in serum lipids. A case report demonstrates that vitamin D supplementation in a patient under total parenteral nutrition can cause hypercalcemia. The isolated administration of vitamin B1, without concomitant vitamin B6 and nicotinamide may precipitate potentially life-threatening pellagra encephalopathy. Repeat blood transfusions may produce clinically overt organ hemosiderosis, e.g. cirrhosis of the liver, diabetes mellitus or myocardiopathy. The literature contains reports on a few cases of sarcoma associated with orthopedic metal implants. The controversial issue of the potential dangers of dental amalgams is briefly mentioned.
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PMID:[Vitamins and metals: possible hazards for humans]. 866 74

Homozygous transfusion-dependent beta-thalassemia patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Short stature, delayed sexual maturation, diabetes mellitus, hypothyroidism, hypoparathyroidism, and metabolic bone disease can and should be diagnosed as early as possible so that the intervention can be fruitful. Primary or secondary amenorrhea is due primarily to pituitary gonadotrope hemosiderosis, as attested by pathology data and the demonstration in vivo of nonstimulable follicle-stimulating hormone and luteinizing hormone release and secretion after the exogenous administration of gonadotropin-releasing hormone or its agonistic analogs. Ovulation can be achieved with the use of exogenous gonadotropins provided that the ovary has no siderosis (as seen in neglected patients) or damage induced by drugs used for bone marrow transplantation. Once pregnancy is achieved, it should be considered high risk and be dealt with or cared for by an expert team to ensure a successful outcome.
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PMID:Reproductive health in patients with beta-thalassemia. 895 76


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