Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin (EPO) possesses generalized neuroprotective and neurotrophic actions. We tested the efficacy of recombinant human EPO (rhEPO) in preventing and reversing nerve dysfunction in streptozotocin (STZ)-induced diabetes in rats. Two days after STZ [60 mg/kg of body weight (b.w.), i.p.], diabetic animals were administered rhEPO (40 microg/kg of b.w.) three times weekly for 5 weeks either immediately (preventive) before or after a 5-week delay (therapeutic) after induction of hyperglycemia or at a lower dose (8 microg/kg of b.w. once per week) for 8 weeks (prolonged). Tail-nerve conduction velocities (NCV) was assessed at 5 and 11 weeks for the preventive and therapeutic schedule, respectively. Compared to nondiabetic rats, NCV was 20% lower after 5 weeks in the STZ group, and this decrease was attenuated 50% by rhEPO. Furthermore, the reduction of Na(+),K(+)-ATPase activity of diabetic nerves (by 55%) was limited to 24% in the rhEPO-treated group. In the therapeutic schedule, NCV was reduced by 50% after 11 weeks but by only 23% in the rhEPO-treated group. rhEPO treatment attenuated the decrease in compound muscle action potential in diabetic rats. In addition, rhEPO treatment was associated with a preservation of footpad cutaneous innervation, as assessed by protein gene product 9.5 immunostaining. Diabetic rats developed alterations in mechanical and thermal nociception, which were partially reversed by rhEPO given either in a preventative or therapeutic manner. These observations suggest that administration of rhEPO or its analogues may be useful in the treatment of diabetic neuropathy.
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PMID:Erythropoietin both protects from and reverses experimental diabetic neuropathy. 1471 63

This paper presents the role of erythropoietin application in diabetic patients with accompanying renal failure. The main cause of anemia in diabetics are: nephropathy, structural lesions of erythrocyte membrane and blood loss connected with diagnostic and therapeutic actions. There are publications which demonstrate that in patients with diabetes type 1 or 2 with accompanying nephropathy, anemia appears more frequently than in the group of patients with chronic renal failure caused by other factors. It is supposed, that the impaired erythropoietin synthesis in diabetics can be caused by autonomic neuropathy. Erythropoietin administration in case of diabetic nephropathy has a beneficial influence on fat metabolism, immune response and reduction of insuline resistance. Erythropoietin because of reduction of vascular endothelial growth factor synthesis blocks the development of diabetic retinopathy and macroangiopathy. Erythropoietin reduces the risk of the left-ventricular hypertrophy caused by anemia. Very important is that the erythropoietin resistance is lower in diabetics. Scientists who are adverse to erythropoietin administration in patients with diabetic nephropathy maintain, that it can lead to vascular complications and the deterioration of glycemia control.
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PMID:[Erythropoietin administration in diabetic patients]. 1497 47

Anaemia is a common complication of chronic kidney disease (CKD). It is often more severe and occurs at an earlier stage in patients with diabetic nephropathy than in patients with CKD of other causes. This anaemia results from erythropoietin deficiency, which seems to develop in patients with type 1 diabetes even at relatively "normal" levels of serum creatinine. Early erythropoietin- deficiency anaemia occurs in both type 1 and type 2 diabetes, although the prevalence may be higher in type 1 diabetes. However, numerically most patients with erythropoietin-deficiency anaemia have type 2 diabetes as it is a much more common disease. There is also a greater prevalence in women than men but this is not related to iron stores. In addition, erythropoietin-deficiency anaemia is associated with the presence of autonomic neuropathy in patients with diabetes. Small studies have suggested that recombinant human erythropoietin (rhEPO; epoetin) treatment is effective in correcting erythropoietin-deficiency anaemia in patients with diabetes. Additionally, rhEPO therapy improves quality of life and well-being in these patients. Studies also suggest that treatment with rhEPO to restore a normal haematocrit ameliorates orthostatic hypotension. Given the high cardiovascular risk in patients with diabetic nephropathy, it is important to determine in prospective clinical trials whether early anaemia correction can also improve cardiovascular outcomes.
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PMID:Anaemia in diabetes. 1510 43

The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.
Diabetes 2004 Sep
PMID:Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse. 1533 68

Erythropoietin (Epo) has been reported to inhibit apoptosis of neuron and erythroid cells. In this study, we examined an effect of high glucose on apoptosis of endothelial cells and investigated an anti-apoptotic effect of Epo. Human aortic endothelial cells were incubated with normal or high glucose for 72 h, and apoptotic cells were detected by TUNEL assay. Simultaneously, Epo (100 U/ml) was added to the high glucose medium to examine an inhibitory effect on the apoptosis induced by high glucose. Activity of caspase-3 was also measured using a specific substrate. To investigate a possible mechanism of Epo's action on apoptosis, phosphorylation of Akt was examined by applying Epo. Incubation with high glucose increased apoptosis of endothelial cells, whereas this effect was prevented by co-incubation with Epo. Caspase-3 activity was also increased (1.4-fold) by incubation with high glucose, and the activation of caspase-3 was normalized to the control level by co-incubation with Epo. Furthermore, Epo-induced phosphorylation of Akt in dose-dependent manner. In conclusion, we demonstrated that incubation with high glucose activated caspase-3 and induced apoptosis of endothelial cells. Epo was shown to phosphorylate Akt, leading to the inhibition of caspase-3 activation and apoptosis induced by high glucose. These results suggest that reduced production of Epo in patients with end-stage of nephropathy may accelerate diabetic angiopathy and that replacing therapy with Epo might inhibit endothelial cell apoptosis and diabetic angiopathy.
Diabetes Res Clin Pract 2004 Dec
PMID:Effect of erythropoietin on endothelial cell apoptosis induced by high glucose. 1556 57

The aim of this work was to investigate the interrelated effects of glucose, nitric oxide (NO) and erythropoietin on neuronal survival in retinal cultures, thereby exploring the mechanism of neuronal death in the diabetic retina. Rat retinal cells were cultured in low (5 mM) or high (15 mM) glucose concentrations. After 9 days, cell viability was assessed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and NO production was determined by the Griess reaction. Immunohistochemistry was used to quantify GABA-labelled neurones and cells staining for DNA breakdown. High or low glucose concentrations had no effect on basal NO production or the survival of neurones in culture, but treatment with N-nitro-L-arginine methyl ester reduced extracellular levels of NO and increased neuronal survival at both concentrations of glucose. Erythropoietin decreased cell death and NO levels, but only in cultures grown in low concentrations of glucose. It is concluded that erythropoietin's neurotrophic function in the retina is attenuated at glucose concentrations similar to those which occur in diabetes.
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PMID:Neuronal death in primary retinal cultures is related to nitric oxide production, and is inhibited by erythropoietin in a glucose-sensitive manner. 1565 19

Erythropoiesis indices, number of leucocytes in 1 ml of blood, leukocytic formula, lymphocytes immunophenotype in the patients' blood with diabetes mellitus complicated with diabetic neuropathy and marked normochromal anemia after the treatment with Erythropoietin b have been analyzed in the study. Significant increase in haemoglobin, erythrocytes content, hematocrit indices of peripheral blood has been observed during the treatment. The patients felt better, their quality of life improved, CD3+, CD4+, CD5+ cells and granule-contained lymphocytes content normalized. Serious adverse affects of the medication haven't been observed in the study.
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PMID:[Effect erythropoietin-beta on parameters of erythropoiesis and immunity in patients with diabetes mellitus complicated with diabetic neuropathy and anemia]. 1572 24

Porphyria cutanea tarda (PCT) is the most common type of porphyria. There is an association of PCT with haemochromatosis, diabetes mellitus and hepatitis C infection. The basis of treatment of PCT consists of three elements: avoidance of triggering factors, iron depletion and porphyrin elimination. Alcohol and certain systemic medical drugs, such as oestrogens (or tuberculostatics), should be considered as triggering factors, and as far as possible, avoided. Other triggering factors, such as chronic haemodialysis in renal insufficiency, need a different approach. The hallmark in iron depletion is phlebotomy. Porphyrin elimination is achieved using low-dose chloroquin therapy. The treatment is safe and effective but has its limits in cases with haemochromatosis (HFE) gene mutations. Here iron depletion needs additional phlebotomy. In patients with chronic haemodialysis-associated PCT, chloroquine is ineffective. Erythropoietin, desferroxamine and small-volume phlebotomy have been employed to control the disease. Childhood PCT is very rare. No controlled studies are available, but published experience suggests that body weight-adapted chloroquine therapy or small volume phlebotomy might be useful.
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PMID:Therapy of porphyria cutanea tarda. 1579 29

The combination of diabetes and chronic kidney disease is associated with increased mortality and reduced quality of life. Recent studies have shown that, in general, late referral of patients to the renal unit increases mortality, and that patients with diabetes who are referred late have a particularly poor prognosis. Several co-morbid conditions have been shown to contribute to poor patient outcomes, including both cardiovascular disease and anaemia. In patients with diabetic nephropathy, anaemia is more severe and is seen earlier than in patients with non-diabetic renal disease. Although the treatment of anaemia with recombinant human erythropoietin (rhEPO; epoetin) is well established, the only data currently available concerning the effects of early intervention in patients with diabetic nephropathy are from small-scale studies. Therefore, two large-scale studies have been designed to provide information on the efficacy of epoetin treatment and on how current management strategies might be improved. The Anaemia CORrection in Diabetes (ACORD) study will provide information on the potential cardiac benefits of early anaemia management in patients with early, type 2 diabetic nephropathy. The Individualised Risk-profiling In DIabEtes Mellitus (IRIDIEM) study will provide evidence-based guidance in risk factor management, by assessing the efficacy of individualized interventions.
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PMID:Managing anaemia and diabetes: a future challenge for nephrologists. 1595 22

Current guidelines give evidence-based advice on how best to manage anaemia in patients with renal disease, but these guidelines do not consider individual patient needs, so tailoring anaemia management to each patient still remains a challenge for the treating physician. Two case studies are described that illustrate some of the key factors that need to be considered. The first case emphasizes that haemoglobin (Hb) targets recommended in current guidelines may not suit all patients. The patient had been stably maintained on subcutaneous epoetin therapy with an average Hb concentration of >13.0 g/dl because he developed angina symptoms when his Hb level fell to 12.2 g/dl. Iron deficiency was identified as the likely cause of falling Hb in this patient. After the patient's iron supplementation was increased, his Hb level was normalized back to >13.0 g/dl without increasing the epoetin dose, and the angina symptoms were resolved. The second case involved a pre-dialysis patient with diabetes, who required a higher dose of epoetin after beginning concomitant antihypertensive treatment with an angiotensin-converting enzyme inhibitor. Previously, the treatment of renal anaemia in pre-dialysis patients has not been the focus of attention. Two ongoing randomized controlled trials have been designed to study early initiation of epoetin treatment in pre-dialysis patients and will provide much needed information in this area.
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PMID:Individualizing anaemia treatment: a discussion of case histories. 1595 26


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