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

Chromium(III) has been reported to be an essential trace element involved in the control of glucose metabolism by insulin. We have studied the distribution and kinetics of intravenous [51Cr]chromium(III) in six human subjects using a whole-body scintillation scanner, a whole-body counter, and plasma counting. Principal concentrations were found in the liver, spleen, soft tissue, and bone. The data were fit to a model consisting of a plasma pool in equilibrium with fast (T1/2 = 0.5-12 h), medium (1-14 days), and slow (3-12 mo) compartments, and transfer rates were calculated for exchanges between compartments. Each of the imaged organs appeared to contain varying proportions of each compartment. Two patients with hemochromatosis, in which iron overload is postulated to exclude chromium transport, were found to have altered rate constants. The results should be useful in assessing the metabolism and nutritional requirement of chromium(III) in humans and its importance in disease processes such as diabetes.
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PMID:Kinetics of trace element chromium(III) in the human body. 683 62

To evaluate the roles of alcohol and genetic factors in hepatic iron overload, we studied prospectively 61 patients selected solely on the basis of increased stainable hepatic iron (grade 3 or 4). Independent comparisons were made between alcoholic (n = 20) and nonalcoholic (n = 41) patients, and between patients wih affected relatives (n = 25) and those without (n = 36). For the entire group, the mean value for mobilizable iron was 19.6 g and the prevalence of HLA-A3 was 69.6%, both findings compatible with genetic hemochromatosis. Subgroups were no different in clinical features (diabetes, pigmentation, cardiomyopathy, hypogonadism, or arthropaty), histologic findings (fat, inflammation, fibrosis), indexes of iron metabolism (serum iron, transferrin saturation, chelatable iron, and mobilizable iron stores), or frequency of HLA-A3 and HLA-B7. The only exception was that mean hepatic iron concentration was lower in alcoholic patients than in nonalcoholic patients (17,344 vs. 28,553 micrograms/g dry wt, p less than 0.001). Similarity between subgroups in almost all parameters examined is consistent with the hypothesis that heavy deposition of hepatic iron, as observed in our patients, is an indication of genetic hemochromatosis, regardless of alcohol consumption or the findings of affected relatives. The lower concentrations of hepatic iron in alcoholic patients, despite equal body stores in both groups, suggest that alcohol may alter the distribution of storage iron in genetic hemochromatosis.
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PMID:Hemochromatosis: genetic or alcohol-induced? 684 Apr 75

The etiology of diabetes in some conditions of iron overload is not known. We studied growth, glucose tolerance, and pancreatic islet cell morphology and cytochemistry in rats administered parenteral FeNTA. These rats developed glucosuria, slowing of growth with eventual weight loss, polyuria, polydipsia, and death. They had normal fasting plasma glucose levels but decreased glucose tolerance and insulin response to glucose. Although no Prussian blue staining of iron was observed in pancreatic islets by light microscopy, at the ultrastructural level insulin-secreting beta-cells showed ferrin iron deposits localized to the plasmalemma and the cytoplasmic surface of secretory granule membranes. Prussian blue staining was also observed in parenchymal cells of the liver, heart, and kidney, in order of decreasing intensity. Animals treated with an equivalent dose of NTA, saline, or iron-dextran in saline had normal growth and response to glucose and did not exhibit pancreatic iron deposits at the light or ultrastructural level. These results support the hypothesis that iron affects pancreatic islet cell function and may be an etiologic agent of diabetes mellitus in hemochromatosis.
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PMID:Iron nitrilotriacetate--induced experimental diabetes in rats. 698 19

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

This paper presents a review of the significant body of literature liking dietary iron overload, not only to heart disease, but also to cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. Following an analysis of our understanding of the mechanistic role iron plays in oxidative damage, an interpretation of the fact that plasma concentrations of several antioxidants are decreased in the presence of disease is offered. Evaluation of (1) age-related dietary trends over time and (2) factors involved in iron absorption leads to the hypothesis that the combination of citric acid and ascorbic acid (a synergistic pair of strong enhancers) is instrumental in causing a deleterious increase in iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of the diseases mentioned; therefore, the synergistic combination of citric and ascorbic acids may play a major role in our worsening disease statistics. Evidence to support this hypothesis and possible experiments to test it are included. This combination needs further study, particularly because the iron overload produced may be correctable.
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PMID:Proposed role for a combination of citric acid and ascorbic acid in the production of dietary iron overload: a fundamental cause of disease. 755 10

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

Idiopathic hemochromatosis, the most frequent inherited disease in Caucasians, is frequently undiagnosed. In this disorder, characterized by a continued inappropriated absorption of dietary iron, the clinical manifestations result from damage to those organ systems in which iron has been pathologically deposited, namely, the heart and the liver. Typically, hemochromatosis becomes clinically manifest in later life and in men more frequently than in women. This has been attributed to the extra loss of iron in women through menstruation and pregnancies. Removal of the excess iron by phlebotomy will prevent all of the complications of hemochromatosis of when begun early. In this paper, we report a case of a young woman with a eight years evolution of amenorrhea, cardiac failure, diabetes mellitus and increased pigmentation of the skin, associated with biochemical markers of iron overload. It is emphasized that hemochromatosis most be excluded in all patients with a unexplained cardiac failure.
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PMID:[Refractory heart failure in a 26-year-old woman with idiopathic hemochromatosis]. 783 64

Haemochromatosis is one of the most common inborn errors of metabolism. In prospective epidemiological studies the frequency of haemochromatosis is 0.0037 (76/20333 subjects) for homozygotes which corresponds to a gene frequency of 0.061 and a frequency of heterozygotes of 0.115. Abnormality in liver function tests, weakness and lethargy, skin hyperpigmentation, diabetes mellitus, arthralgia, impotence and ECG abnormalities are the most frequent findings and symptoms at diagnosis. In recent years about 50% of patients were detected without having liver cirrhosis and 20% of patients did not have any symptoms and pathology except iron overload. Survival analyses in long-term studies showed that in the absence of cirrhosis and diabetes, iron removal by phlebotomy therapy prevents further tissue damage and guarantees a normal life expectancy. Patients with massive and long-lasting iron overload had a worse prognosis than those with less severe iron excess. Iron removal in general ameliorated liver disease, weakness and cardiac abnormalities, and also prevented the progression of endocrine alterations. Therapy, however, did not influence insulin-dependent diabetes. Most deaths in patients with hereditary haemochromatosis were caused by liver cancers which often occurred many years after complete iron removal. In patients with haemochromatosis, liver cirrhosis, cardiomyopathy, and diabetes mellitus are also significantly more frequent causes of deaths when compared with the general population. Further strategies have to evaluate the design of screening programmes in order to diagnose more patients in the precirrhotic and asymptomatic stage.
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PMID:Clinical spectrum and management of haemochromatosis. 788 Nov 58

Long-term blood transfusions lead to the accumulation of iron that in the absence of chelation therapy causes complications such as liver cirrhosis, growth failure, hypogonadism, hypothyroidism, hypoparathyroidism, diabetes and myocardiopathy. The last still represents the most frequent cause of death in haemosiderotic transfusion-dependent patients. At the moment the only chelator widely used is desferrioxamine (DFX). The drug works best when administered as a continuous infusion, mainly by the subcutaneous route. To patients with severe iron overload, impending organ failure, or poor compliance to chelation, DFX can be administered intravenously, through an externalized central catheter or, preferably, a subcutaneous port. Several studies have shown the effectiveness of DFX in reducing the iron burden, thus preventing the complications, once considered inevitable, of iron overload, and even in reverting some, but not all, of the iron-induced dysfunctions. Practical and psychological support are necessary to ensure satisfactory compliance with a therapy that is cumbersome and difficult. Toxic effects of DFX such as growth failure, hearing impairment and bone abnormalities seem to occur mainly in patients who have received high doses of DFX despite a low iron burden. Visual loss and renal and pulmonary toxicities, on the contrary, seem to be more directly related to high DFX peak doses administered irrespective of the patient's amount of iron overload. After bone marrow transplantation, phlebotomy or erythrocytoapheresis might be necessary to reduce further the iron accumulated during years of transfusions.
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PMID:Clinical manifestations and therapy of transfusional haemosiderosis. 788 Nov 60

Insulin resistance and hyperinsulinemia have been reported in homozygous beta-thalassemia before the development of diabetes. However, insulin sensitivity (SI) has never been studied in normoinsulinemic patients. Furthermore, whether hyperinsulinemia is due to increased beta-cell secretion or to decreased hepatic insulin extraction is poorly understood. We estimated SI, beta-cell secretion, and hepatic insulin extraction using the minimal model analysis of a frequently sampled intravenous glucose tolerance test (2.8 g/m2) in two groups of nondiabetic pubertal patients with homozygous beta-thalassemia (seven hyperinsulinemic and seven normoinsulinemic patients) and seven control subjects matched for age, body mass index, and pubertal stage. In both thalassemic groups, SI was reduced by approximately 40% (3.52 +/- 0.57 and 3.74 +/- 0.66 v 6.89 +/- 1.02 10(-4).min-1 [microU/mL], P = .011) and was inversely correlated with iron overload (r = -.707, P = .006). All parameters of beta-cell secretion were not significantly different in patients and controls. On the other hand, basal posthepatic insulin delivery (BDR) was more than doubled in hyperinsulinemic patients with respect to normoinsulinemic patients or controls (15.1 +/- 2.4 v 6.1 +/- 1.1 and 7.5 +/- 2.3 pmol/L.min-1, P = .012), and the same was true for total posthepatic insulin delivery ([TID] 6.3 +/- 1.0 v 2.9 +/- 0.5 and 2.9 +/- 0.7 pmol/L.240 min-1, P = .015). Hepatic insulin extraction was significantly lower in hyperinsulinemic patients than in normoinsulinemic patients or controls (49.3% +/- 9.4% v 73.0% +/- 3.7% and 77.4% +/- 3.9%, P = .011), and in patients it was inversely correlated with iron overload (r = -.829, P = .0001). In conclusion, insulin resistance is present even in normoinsulinemic patients, beta-cell responsiveness to glucose is normal, and hyperinsulinemia is mainly due to decreased hepatic insulin extraction. In nondiabetic thalassemic patients, these defects are possibly related to iron overload.
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PMID:Insulin resistance and hyperinsulinemia in homozygous beta-thalassemia. 788 70


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