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

An obese 76-year-old woman with type II diabetes, hypertension, coronary artery disease, and gastroesophageal reflux was found to have a 6-cm lower-pole mass in a solitary functional right kidney. Because her religious beliefs prohibited blood transfusion, minimally invasive surgery--a laparoscopic partial nephrectomy--was performed, with a good result. Minimally invasive surgery, perhaps with administration of erythropoietin, iron-dextran, or both, is often a good option for severely anemic patients or those whose religious beliefs are opposed to transfusion. Methods of minimizing blood loss intraoperatively are reviewed.
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PMID:Laparoscopic nephron-sparing surgery in a Jehovah's Witness patient. 1500 56

Diabetic nephropathy has become the most prevalent cause of end-stage renal disease (ESRD) in many countries. ESRD patients with diabetes have a particularly poor prognosis compared with patients without diabetes. The course of diabetic nephropathy can be modified with early management of the condition and it is important that diabetes patients are screened regularly for early signs of kidney damage. Blood pressure control and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have been shown to slow the progression of chronic kidney disease. Patients with diabetes are at considerable risk of cardiovascular complications, and modifiable cardiovascular risk factors, such as anaemia and dyslipidaemia, should be treated at an early stage. Correction of anaemia with recombinant human erythropoietin is associated with improvements in quality of life, functional status, and cardiovascular morbidity and mortality, and may slow the progression of renal disease. Abnormalities in calcium and phosphate metabolism and acidosis may also occur in patients with diabetes and nephropathy and these should be monitored regularly. It is important that patients with kidney disease are detected promptly to allow intervention to slow renal disease progression and to treat modifiable cardiovascular risk factors. Improved collaboration between diabetologists and nephrologists will also ensure that patients receive optimal care.
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PMID:Screening and management of patients with early chronic kidney disease. 1510 42

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

Anaemia is a key component of diabetic nephropathy, but its importance has only recently been recognised. Recombinant human erythropoietin (epoetin) is an established treatment for renal anaemia, and may help to reduce complications associated with diabetic nephropathy, such as cardiovascular disease. The limited experience with the use of epoetin in this patient group prompts the urgent need for clinical data on anaemia correction in early diabetic nephropathy, particularly with regard to benefits on cardiovascular risk reduction. The Anaemia CORrection in Diabetes (ACORD) study will investigate the effects of anaemia correction on cardiac structure and function in patients with early diabetic nephropathy. This 15-month multicentre study will recruit 160 adult patients with diabetes, mild or moderate chronic kidney disease (with creatinine clearance >or=30 ml/min at screening) and moderate anaemia (haemoglobin [Hb], 10.5-13.0 g/dl). Patients will be randomised to one of two groups: the early treatment group will receive subcutaneous epoetin beta (NeoRecormon) at study entry to maintain target Hb levels of 13-15 g/dl, while the control group will reflect current practice and will not receive epoetin therapy until Hb levels decline below 10.5 g/dl. The primary efficacy variable, change in left ventricular mass index, will be evaluated at 15 months following randomisation; secondary efficacy variables will include changes in cardiac structure and function over the study period. The ACORD study should provide valuable information on the benefits of anaemia correction in patients with early diabetic nephropathy. The study will also increase awareness of the importance of treating anaemia associated with diabetes.
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PMID:New strategies in anaemia management: ACORD (Anaemia CORrection in Diabetes) trial. 1510 44

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus, but it is also present in up to 25% of healthy nonobese individuals. The molecular mechanisms causing insulin resistance are not yet fully understood. Recently, overexpression of several potential inhibitors of the insulin receptor tyrosine-kinase activity, a key step in insulin signaling, has been described in insulin-resistant subjects . PC-1 is expressed in many tissues and inhibits insulin signaling either at the level of the insulin receptor or downstream at a postreceptor site. An elevated PC-1 content in insulin target tissues may play an important role in the development of insulin resistance in obesity and type 2 diabetes mellitus. A polymorphism in PC-1 has been demonstrated to be associated with insulin resistance. This was a DNA polymorphism in exon 4 that causes an amino acid change from lysine to glutamine at codon 121 (K121Q). PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction. There is growing evidence that genetic factors play an important role in the development of diabetic nephropathy (DN). Efforts to identify these factors rely primarily on the candidate gene approach; candidate genes for insulin resistance may be considered candidates for DN as well. In a stratified analysis according to duration of diabetes, the risk of early-onset end-stage renal disease (ESRD) for carriers of the Q variant was 2.3 times that for noncarriers. The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. Women with GDM have an increased PC-1 content and excessive phosphorylation of serine/threonine residues in muscle insulin receptors. The postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life. Although widely explored, the true cause of insulin resistance in uremic patients is not entirely elucidated yet. During the last decade it was found that erythropoietin (EPO) therapy, used for correction of anemia in patients with end stage renal failure, ameliorates insulin resistance. An increased lymphocyte PC-1 activity over control was found in hemodialysis patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uremic patients treated with EPO. Current investigations implicate that therapeutic modification of PC-1 expression would be of great benefit for insulin-resistant type 2 diabetics. Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics. Thiazolidinedione (TZD) insulin-sensitizing drugs are a class of compounds that improve insulin action in vivo. Treatment of patients with TZDs seems to have a beneficial effect on most, if not all, components of metabolic syndrome. TZDs have also been used in the treatment of nondiabetic human insulin-resistant states, and have demonstrated an improvement in insulin sensitivity. Although much remains to be learned about PPAR gamma receptor and TZD action, the advent of TZD insulin-sensitizing agents has an enormous impact on our understanding of insulin resistance. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
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PMID:Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. 1520 35

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

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

Decreased blood flow is one of the earliest physiological changes observed after the onset of either clinical or experimental diabetes. The reduction in blood flow is believed to lead to nerve hypoxia, which in conjunction with other metabolic alterations and degenerative processes in different nerve compartments, results in the dysfunction known as diabetic neuropathy. The transcriptional regulator hypoxia-inducible factor-1 alpha (HIF-1alpha) accumulates rapidly under hypoxic conditions and modulates the expression of several target genes that protect tissues against ischemia and infarction. At present it is unclear whether diabetic nerve injury results from an abnormal response of HIF-1alpha and its protective target genes. In the present study we have analyzed the expression and activity of HIF-1alpha and its target genes in diabetic nerves as a first step to determine their possible contribution to the development or maintenance of diabetic neuropathy. We observed a transient increase in the expression of HIF-1alpha that peaked between 4 and 6 weeks and declined 8 weeks after induction of experimental diabetes in rats. The increase in HIF-1alpha in diabetic nerves coincided with a similarly transient increase in the expression of several HIF-1alpha target genes including vascular endothelial growth factor, lactate dehydrogenase and erythropoietin, which subsided 8-10 weeks after induction of diabetes. These results suggest that the transient activation of neurotrophic and angiogenic genes, as opposed to a more sustained effect in response to the chronic injury, may be responsible for the alterations in nerve function and regeneration that characterize the diabetic neuropathy.
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PMID:Transient expression of hypoxia-inducible factor-1 alpha and target genes in peripheral nerves from diabetic rats. 1566 58

Diabetes is known to be a risk factor for the severity of anemia in non-dialyzed patients with renal failure. The aim of this study was to evaluate differences in hemoglobin (Hb) response to erythropoietin (EPO) in diabetic and nondiabetic patients on chronic hemodialysis (CHD). Sixty-four patients on CHD were included in the study: 24 type 2 diabetics (mean age, 59+/-11 years; 10 men, 14 women) and 40 nondiabetics (age, 53+/-14 years; 21 men, 19 women). All patients received a fixed dose of 50 mg ferric saccharate and EPO per week, dosed individually to achieve a target Hb level of 12 g/dl. Hb levels, ferritin, transferrin saturation (TSAT), EPO requirement (IU/kg/week), folic acid, vitamin B12 and C-reactive protein (CRP) were measured every two months. Additionally, the incidence of infectious diseases during the observation period of six months was evaluated, and a univariate correlation analysis of CRP and EPO requirements was performed in both groups. Patients with and without diabetes were divided into two groups each: those with normal CRP and those with elevated CRP. The EPO requirements of these groups were compared. Under identical iron substitution the mean Hb level increased more, but not significantly, in non-diabetic patients than in diabetic patients. After 6 months the mean Hb levels were 12.1+/-1.2 versus 11.5+/-1.2 g/dl (NS), although the actual EPO requirement was higher in diabetic than in non-diabetic subjects (244+/-122 versus 183+/-118 IU/kg/week; p<0.05). CRP after 6 months was significantly higher in diabetic than in non-diabetic patients (2.6+/-2.2 versus 1.5+/-1.3 mg/dl; p<0.05), as was the incidence of infectious disease (n/patient/month) (0.24 versus 0.08; p<0.05). The correlation coefficient between CRP and EPO requirements was statistically significant in both diabetic (r=0.547 p<0.01) and non-diabetic subjects (r=0.577; p<0.001). All other laboratory indices were similar in both groups. In the diabetic patients with normal CRP (n=6) the Hb levels achieved after six months were similar to those of non-diabetic patients (n=10) with normal CRP (11.9+/-1.1 versus 12.1+/-1.2%), and the required EPO was comparable. We conclude that the Hb response to EPO is reduced in diabetic patients on CHD. This elevated EPO requirement may be explained by a greater prevalence of infectious diseases, characterized by a significantly higher CRP level, in these patients. Other causes for the elevated EPO requirement could be excluded.
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PMID:Erythropoietin requirement in patients with type 2 diabetes mellitus on maintenance hemodialysis therapy. 1569 Sep 69

Heart failure (HF) in elderly patients is associated with more diffuse symptoms and signs due to the presence of other noncardiac comorbidities. This can cause difficulties in assessing the correct diagnosis and initiating appropriate therapy. The four most frequently occurring noncardiac comorbidities and therapies used to treat them are discussed in the present paper. Hypertension is an important precursor of HF, and is still the most common risk factor for HF in the general population. About 50% of patients with untreated hypertension will develop HF. Pressure overload leads to the development of left ventricular hypertrophy (LVH) and diastolic dysfunction. Diabetes, which occurs in about 20-30% of patients with HF, is an important comorbidity resulting in morphological and metabolic disturbances affecting myocardial blood flow and hormonal regulation leading to a poor outcome and necessitating aggressive conventional treatment. Chronic obstructive pulmonary disease (COPD), occurs in approximately 20-30% of heart failure patients, and may complicate HF treatment, it is therefore important to recognize and treat it effectively. Finally, the early detection of anemia, which occurs in 20-30% of HF patients, is important since it is associated with functional impairment and increased mortality and morbidity. Combined treatment with erythropoietin and intravenous iron has shown beneficial effects on clinical symptoms and morbidity. In conclusion early detection of concomitant diseases in patients with HF is important and should be considered carefully when initiating therapy.
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PMID:Frequent non-cardiac comorbidities in patients with chronic heart failure. 1571 70


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