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

Embryonic dysmorphogenesis has been blocked by antioxidant treatment in vivo and in vitro, suggesting that embryonic excess of reactive oxygen species (ROS) has a role in the teratogenic process of diabetic pregnancy. We report that the basal levels of ROS in dispersed rat embryonic cells in vitro, as determined by fluorescence of dichlorofluorescein (DCF), were not different in cells from control and diabetic pregnancy at day 10 or 12. Beta-hydroxybutyrate (beta-HB) and succinic acid monomethyl ester both augmented DCF fluorescence in cells from day 12 embryos of normal and diabetic rats but not from day 10 embryos. Cells of day 10 and day 12 embryos from normal and diabetic rats responded to increasing glucose concentrations with a dosage-dependent alleviation of DCF fluorescence. Day 10 embryonic cells exhibited high glucose utilization rates and high pentose phosphate shunt rates, but low mitochondrial oxidation rates. Moreover, in vitro culture of embryos between gestational days 9 and 10 in the presence of 20% oxygen induced an increased and glucose-sensitive oxidation of glucose compared with embryos not cultured in vitro. At gestation day 12, however, pentose phosphate shunt rates showed a decrease, whereas the mitochondrial beta-HB oxidation rates were increased compared with those at gestation day 10. This was paralleled by a lower expression of glucose 6-phosphate dehydrogenase- and phosphofructokinase-mRNA levels at day 12 than at day 10. On the other hand, H-ferritin mRNA expression at day 12 was high compared with day 10. None of the mRNA species investigated were affected by the diabetic state of the mother. It was concluded that beta-HB-induced stimulation of mitochondrial oxidative events may lead to the generation of ROS at gestational day 12, but probably not at day 10, when only a minute amount of mitochondrial activity occurs. Thus our results do not support the notion of diabetes-induced mitochondrial oxidative stress before the development of a placental supply of oxygen.
Diabetes 1998 Feb
PMID:Beta-hydroxybutyrate increases reactive oxygen species in late but not in early postimplantation embryonic cells in vitro. 951 22

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.
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PMID:Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. 954 28

Hereditary ceruloplasmin deficiency with hemosiderosis (aceruloplasminemia) is a newly recognized autosomal recessive disorder of copper-iron metabolism due to mutations in the ceruloplasmin (Cp) gene. We report here a novel mutation in the Cp gene in a 54-year-old Japanese woman with this disease. She showed clinical triad; diabetes mellitus, retinal degeneration and neurological disorder in her middle age. Laboratory findings were characteristic for no detectable serum ceruloplasmin and increased serum ferritin. Liver biopsy revealed excessive storage of iron in hepatocytes and magnetic resonance imaging of the brain was indicative of increased iron content in the basal ganglia, thalamus and dentate nucleus. The a-->g substitution at the splice acceptor site of the intron 6 (1209-2) caused a 8-bp deletion in Cp mRNA by defective splicing, resulting in a premature termination codon at the amino acid position 388. Truncation of Cp, even if effectively translated, may cause loss of its normal function because of drastic change in its triangular structure.
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PMID:A novel splicing mutation in the ceruloplasmin gene responsible for hereditary ceruloplasmin deficiency with hemosiderosis. 955 83

To investigate how cigarette smoking increases the risk of cardiovascular disease, risk factors were compared between 166 cigarette smokers and 312 non-smokers, in a random sample of males (Chinese, Malays and Asian Indians) aged 30-69 years from the general population of Singapore. There was adjusted for age and ethnic group. The prevalence of hypertension was lower in cigarette smokers (15.2%) than non-smokers (21.9%), with the difference reduced by adjustment for body mass index (BMI). Smokers had: lower mean serum HDL-cholesterol (0.76 versus 0.81 mmol/l) and higher mean serum fasting triglyceride (1.92 versus 1.71 mmol/l), which will increase atherosclerosis; higher mean plasma fibrinogen (2.75 versus 2.67 g/l) and plasminogen activator inhibitor 1 [PAI-1] (24.9 versus 22.2 ng/ml), which will increase thrombosis; and lower mean plasma vitamin C (4.4 versus 6.4 mg/l) and serum selenium (118 versus 123 microg/l), which may increase atherosclerosis. Adjustment for BMI slightly increased the differences for HDL-cholesterol, fasting triglyceride, fibrinogen and PAI-1, indicating that less generalised obesity among smokers reduces their increased cardiovascular disease risk. Smoking was not found to be related to: diabetes mellitus; serum total cholesterol, LDL-cholesterol, apolipoproteins A1 and B and lipoprotein(a); plasma factor VIIc and prothrombin fragment 1 + 2; and plasma vitamins A and E and serum ferritin. There was no evidence of increased insulin resistance in smokers, as measured by mean fasting serum insulin.
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PMID:Cardiovascular risk factors in relation to cigarette smoking: a population-based survey among Asians in Singapore. 962 68

We studied survival and disease complications in 1,146 patients with thalassemia major, born from January 1, 1960 to December 31, 1987. At last follow-up, in March 1997, probability of survival to age 20 years was 89% and to age 25 years was 82% for patients born in the years 1970-1974. Patients who died had a serum ferritin level, measured the year before death, significantly higher than those who survived. Diabetes was present in 5.4% of the patients; heart failure in 6.4%; arrhythmias in 5.0%, thrombosis in 1.1%, hypothyroidism in 11.6%, HIV infection in 1.8%. Hypogonadism was diagnosed in 55% of 578 patients who had reached pubertal age: 83.5% of hypogonadic females and 78.6% of males were receiving substitutive hormonal therapy. In conclusion, the survival of patients with thalassemia major is good and improving, but the prevalence of severe complications is still high.
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PMID:Survival and disease complications in thalassemia major. 966 44

Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis was that high iron status was associated with increased oxidation of LDL. The associations of serum ferritin (a marker of iron status) and dietary iron intake with the susceptibility of LDL to in vitro oxidation (lag phase) and autoantibodies against MDA-modified LDL (two markers of oxidation stress) were examined among 281 men and 192 women with a mean age of 59 years (S.D. = 5) who participated in the Atherosclerosis Risk in Communities (ARIC) Study visit 2 in 1990 through 1992. Lag phase duration and the autoantibodies against MDA-modified LDL were weakly correlated with each other (r = 0.19, P = 0.001 in men; r = 0.15, P = 0.03 in women). In linear regression analysis adjusting for age, field center, blood storage time, and carotid atherosclerosis case-control status, there was no association between ferritin level and the lag-phase, or between ferritin level and autoantibodies against MDA-modified LDL in either sex. Further adjustment for traditional cardiovascular risk factors (smoking, vitamin supplement use, body mass index, LDL cholesterol, hypertension and diabetes) did not alter these null results. Ferritin was significantly and positively correlated with body mass index in both sexes (r = 0.21 among men and r = 0.22 among women) and with the waist-to-hip ratio among women (r = 0.26). In addition, among women, ferritin was positively correlated with orosomucoid (r = 0.24) and with sialic acid (r = 0.19). Dietary iron was not associated with the parameters of LDL oxidation or with ferritin level. These findings do not support a role of body iron stores in promoting oxidation of LDL.
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PMID:Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis Risk in Communities. 969 7

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.3 years ago (range 6-13 years) and 465 patients who underwent DS 4.1 years ago (range 1.7-6.0 years). The questionnaire response rate was 93%, and laboratory work was completed for 65% of both groups. The mean weight loss after DG was 37 +/- 21 kg and after DS 46 +/- 20 kg. There were fewer side effects after DS: The number of daily stools was lower (p < 0.0002), as was the prevalence of diarrhea (p < 0.01), vomiting (p < 0.001), and bone pain (p < 0.001). Greater benefits related to several aspects of life were reported after DS than DG (p < 0.0001). The mean serum levels of ferritin, calcium, and vitamin A were higher (p < 0.001), and parathyroid hormone was lower. The yearly revision rate for excessive malabsorption was 1.7% per year after DG and 0.1% per year after DS. The two procedures were equally efficient for treating co-morbid conditions such as diabetes, hypertension, and hypercholesterolemia. Biliopancreatic diversion with sleeve gastrectomy/duodenal switch and a 100-cm common limb was shown to produce greater weight loss with fewer side effects.
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PMID:Biliopancreatic diversion with duodenal switch. 971 20

Genetic haemochromatosis (GH) is one of the most common hereditary diseases, with a prevalence of 1-5/1000 in the Western world. In 90 per cent of cases a mutation is found in an MHC-class-like gene designated HFE, involving a substitution at position 282 of the HFE protein and resulting in defective binding of beta(2)-microglobulin. Animals with beta(2)-microglobulin deficiency develop iron overload, indicating this protein to be involved in the regulation of iron metabolism. Hepatic iron overload results in increased production of oxygen free radicals and peroxidation of membrane lipids, thus causing damage to lysosomes, mitochondria and the endoplasmic reticulum. These cellular events may progress to cell death, fibrogenesis, and the development of liver cirrhosis which is associated with a 200-fold increase in risk of hepatocellular carcinoma. In addition to the risk of diabetes, arthralgia, cardiac arrhythmia, pituitary insufficiency and hypogonadism, iron excess is also associated with aggravation of the cytotoxic effects exerted on hepatocytes by other agents such as alcohol or hepatotrophic viruses. The treatment of iron overload in GH consists of weekly venesection until the serum ferritin level is normalized, followed by maintenance therapy. Survival rates are normal if the disease is detected and treated before complications have developed.
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PMID:[Defective iron metabolism in genetic hemochromatosis. The mechanisms remain unknown in spite of genetic advances]. 972 62

The structural alterations of endothelium and smooth muscle cells of the hind limb and heart veins and arteries were investigated in Golden Syrian hamsters subjected to streptozotocin induced diabetes. Animals were examined at 5, 10, and 15 weeks after induction of diabetes. At each time point body weight and plasma glucose concentrations were recorded. Anesthetised animals were washed out of blood, fixed in situ, and the femoral vein and artery, saphenous vein and artery, and heart veins and coronaries were dissected out, and processed for electron microscopical examination. Anionic sites of the endothelial plasmalemma were visualized by in situ perfusion of cationized ferritin. The endothelial localization of von Willebrand factor was carried out by immunocytochemistry. The results showed that induction of experimental diabetes generated morphological changes of the endothelium and smooth muscle cells of both hind limb and heart vessels. The common alterations developed in endothelial cells of venous and arterial origin consisted in: 1) the development of a secretory phenotype, enriched in biosynthetic and degradative organelles; 2) the abundance of cytoskeletal elements, especially intermediary filaments; 3) the increase in number of fused plasmalemmal vesicles and transendothelial channels, and 4) the hyperplasia of the basal lamina. In contradistinction to the arterial endothelium, the peculiarities of the venous endothelium in the diabetic hamsters examined were: 1) the uniform distribution of the anionic sites exposed on the luminal plasma-lemma (as in normal animals), and 2) the increased number of copies of Weibel-Palade bodies (up to 13 copies per endothelial cell in the hind limb). Von Willebrand factor was immunodetected in Weibel-Palade bodies, Golgi cisternae and some vesicles of normal and diabetic hamsters. With time, and especially pronounced at 15 weeks of diabetes, the smooth muscle cells of veins and arteries examined exhibited a characteristic secretory phenotype, and were surrounded by a reticulated basal lamina and a hyperplasic extracellular matrix (especially pronounced in arteries). These data indicate that diabetes affects both heart and hind limb veins and arteries, producing structural changes of the endothelium and smooth muscle cells which may account, at least in part, for the specific vascular complications.
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PMID:Diabetes-induced structural changes of venous and arterial endothelium and smooth muscle cells. 985 Oct 55

Iron overload is the main cause of morbidity and mortality in patients with thalassaemia major. In order to establish if the presence of the mutations recently described in the haemochromatosis gene affects the severity of iron overload in thalassaemia patients, we compared the prevalence of mutations C282Y and H63D in 216 young adults regularly transfused and chelated in North-Eastern Italy with the frequency found in a group of blood donors from the same area. For each patient, mean serum ferritin over the last 3 years, liver iron concentration, and the presence of diabetes, hypogonadism and heart disease, were considered. The frequency of the C282Y allele was 1.9% in patients with thalassaemia major and 2.3% in blood donors (P=ns). The frequency of the H63D allele was 16.2% in patients with thalassaemia major and 15.3% in blood donors (P=ns). When age, liver iron concentration and mean yearly serum ferritin levels were compared in patients with and without mutations C282Y and H63D, no significant differences were found. Also, the prevalence of iron-induced complications was not significantly different between patients carrying or not carrying the mutations. The presence of the HH mutations does not seem to influence the degree of iron overload and its consequences in regularly transfused and chelated patients with thalassaemia major.
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PMID:The haemochromatosis mutations do not modify the clinical picture of thalassaemia major in patients regularly transfused and chelated. 985 37


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