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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to investigate the pancreatic function in patients with thalassaemia major, plasma glucose and immunoreactive C-peptide levels were determined in 9 diabetic thalassaemic patients and in 7 controls after arginine infusion. Mean basal and peak values and C-peptide areas in thalassaemic patients did not differ significantly from those of the controls. However, in the thalassaemic group there was a greater variation in values, since pancreatic beta-cell function was found either normal, reduced or increased. These findings could suggest that different factors may lead to diabetes which complicates thalassaemia, i.e. insulin-resistance, probably due to liver damage subsequent to iron deposition and infectious hepatitis, and insulinopenia, probably due to beta-cell lesion following iron storage in the pancreas.
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PMID:Beta-cell function assessed by plasma C-peptide evaluation in diabetic thalassaemic patients. 634 76

Recent developments in recombinant DNA research promise to have a substantial impact on medicine. The technology now allows for DNA pieces to be isolated and ligated to other DNA, such as that from bacteria, and be replicated in foreign hosts. The replicated DNA can then be isolated and used to study its structure, to study gene expression and its regulation, to program microorganisms to synthesize medically, agriculturally or industrally important proteins, to transfer genes back into mammalian cells and to diagnose genetic diseases. The DNA used for cloning can be obtained by copying mRNA, by chemically synthesizing it and by isolating chromosomal DNA; each of these types of DNAs serve special uses. The results of studies with the use of these DNAs have provided an enormous amount of information, in some cases of a quite surprising nature, about the structure and function of genes. This information is already providing substantial insights into the mechanisms of diseases such as cancer and hopefully it will lead to newer therapies as well. The technology had already resulted in the synthesis in microorganisms of a number of useful proteins such as vaccines, insulin and interferon. The use of the DNA to diagnose genetic diseases has been applied as for instance to thalassemia and sickle cell anemia. Finally, the ability to transfer genes back into cells and to have these genes function promises to open a new approach with gene therapy that may be useful for treating not only genetic diseases, but a number of other diseases as well.
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PMID:Tan Sri Runme Shaw lecture. Genetic engineering and its impact on medicine. 635 18

Twenty-one Thai patients with beta-thalassemia/haemoglobin E and haemoglobin H diseases, 8-20-years-old, were studied. These patients had receive none or minimal blood transfusion. The important clinical endocrine abnormalities were growth retardation and sexual immaturity. GH secretion was found to be impaired in the majority of patients. Oral GTT showed chemical diabetes in one out of sixteen tests, a much lower incidence than in thalassaemic patients treated by hypertransfusion in the West. The mean insulin levels basally and after glucose loading were lower than those of the normal controls. Thyroid function was normal in all of the patients. Serum cortisol and 24-h urinary oxogenic steroids 917 OGS) levels were normal, as was adrenal cortical reserve in all the patients. The literature on endocrine function in in thalassaemia is reviewed.
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PMID:Endocrine function in thalassaemia. 726 14

The commonly occurring short stature in the condition of thalassaemia major was investigated with respect to the possible role of the somatomedin growth factor low molecular weight non-suppressible insulin-like activity (NSILAs). Nineteen affected patients (12 boys, 7 girls) aged between 2 and 21 years were studied. Twelve of them were on or below the 10th centile for height of whom 7 were on or below the 3rd centile for height. Serum immunoreactive growth hormone responses to exercise were normal in 9 of 11 subjects tested. Using an isolated fat cell bioassay NSILAs was undetectable in 10 and was more than 2 SD below the normal mean value in the other 9 subjects. High molecular weight NSILA (not a growth factor) was very low or undetectable in all 9 subjects tested. Low molecular weight NSILAs did not show the normal correlation with age in childhood, nor was there any correlation with height, height velocity, or bone age. The 2 children above the 50th centile for height had undetectable NSILAs. There was no evidence of iron or ferritin interfering in the bioassay, and mixing experiments showed no evidence of inhibitory activity towards NSILAs in thalassaemic sera. Low circulating levels of the somatomedin NSILAs may contribute to the short stature in thalassaemia major, but other factors may permit normal growth in some affected children.
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PMID:Deficiency of non-suppressible insulin-like activity in thalassaemia major. 730 29

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

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

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

Growth hormone (GH) secretion was determined by evaluating ultradian GH profiles for 12 h and GH responses to insulin stimulated hypoglycaemia (ITT) in 28 stunted boys with beta-thalassaemia major aged 15.2-17.4 years, who presented with pubertal failure (FP). Healthy non thalassaemia prepubertal boys (n = 10) aged 7.5-8.8 years, were studied as controls. All patients had normal responses to ITT with peak GH levels > or = 15 mU/l. Basal GH concentrations (mean +/- sem) (1.65 +/- 0.03 mU/l vs 2.58 +/- 0.27 mU/l; P < 0.05) and the stimulated GH responses (peak GH = 15.4 +/- 0.20 mU/l vs 21.08 +/- 0.78 mU/l; P < 0.001) were significantly lower in the patients with failed puberty than in the controls, indicating that the FP patients had diminished GH reserve and secretory capacity. Moreover, all the GH peak parameters including the maximum spontaneous concentrations (MX-GH) and the area under the GH curve (AUC) were significantly lower in the thalassaemic patients than in the controls (MX-GH = 5.2 +/- 0.21 mU/l vs 20.42 +/- 0.14 mU/l; P < 0.001; AUCb = 421.22 +/- 4.31 mU/l vs 712.20 +/- 3.42 mU/l; P < 0.001). These observations suggest that the thalassaemic patients had endogenous neurosecretory GH deficiency (GHND). Priming with sex steroid did not cause any improvement in the spontaneous or stimulated GH secretory patterns in thalassaemic patients. It was noteworthy that in neither the patients nor the control subjects, was there a significant correlation between the maximum stimulated and the MX-GH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of growth hormone in thalassaemic boys with failed puberty: spontaneous versus provocative test. 822

Puberty is normally associated with a decline in tissue sensitivity to insulin. However, normal glucose homoeostasis is maintained by compensatory increases in glucose-stimulated insulin secretion. Here we describe studies performed in healthy children which have determined the site of insulin resistance (hepatic vs. peripheral) and whether this resistance extends to other substrates such as amino acid and free fatty acid metabolism. The changes in insulin action and secretion that are normally seen during puberty lead us to question the role of insulin resistance in other childhood conditions that are complicated by the later development of type I or type II diabetes, namely thalassaemia major and Turner's syndrome. These studies showed that in patients with thalassaemia and Turner's syndrome, insulin resistance and increased insulin secretion are very early metabolic defects that appear before the development of diabetes.
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PMID:Insulin-resistant syndromes in children. 826 87

To better understand the pathophysiology of glucose intolerance secondary to iron overload in patients with thalassemia major, we performed tolbutamide-modified frequently sampled iv glucose tolerance tests (FSIGTs) in 10 thalassemic patients (6 males and 4 females; 21.7 +/- 1.2 yr old; body mass index, 19.7 +/- 0.6 kg/m2) and 10 healthy controls (5 males and 5 females; 22.4 +/- 1.3 yr; body mass index, 20.6 +/- 0.5 kg/m2). Insulin secretion and action were quantified by application of the minimal model of glucose kinetics and the combined model of insulin and C-peptide kinetics to the FSIGT data. The insulin sensitivity index was significantly lower in thalassemia patients [72 +/- 12 min-1(nmol/mL)] compared to controls [158 +/- 21 min-1(nmol/mL); P = 0.0026]. The integrated insulin response during the FSIGT was significantly greater in thalassemia patients than in controls after tolbutamide injection (P = 0.042). The difference in insulin levels was apparently due to reduced hepatic insulin extraction in thalassemia (78 +/- 2% vs. 68 +/- 3%; P = 0.0251). Seven of the 10 thalassemia patients were studied prospectively at 6-month intervals for 6-12 months. Repeated measures analysis of variance indicated that across a 6-month interval, there was a decrease in the total integrated insulin response (P = 0.002), with no change in insulin sensitivity (P = 0.86). In conclusion, patients with thalassemia major have significant insulin resistance, which may be compensated for by an elevated circulating insulin level. The elevated insulin level in response to tolbutamide appears to be due to reduced hepatic extraction of insulin and not to an enhanced insulin secretory response. Over time, patients with thalassemia experience a reduction in their circulating insulin levels. Persistent insulin resistance along with a progressive reduction in circulating insulin levels may lead to glucose intolerance and diabetes mellitus, which have a high prevalence in patients with thalassemia major.
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PMID:Factors determining glucose tolerance in patients with thalassemia major. 834 55


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