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Query: UMLS:C0011849 (diabetes)
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Erythropoietin is the primary hormone controlling erythropoiesis in both adults and fetuses. In extra-fetal life the main organ producing erythropoietin is the kidney which is responsible for producing about 90% of the total amount of this hormone. In fetal life erythropoietin is produced by the liver of the fetus. The erythropoietin production depends on the content of oxygen in blood. This is probably the only physiological stimulus which regulates the production of erythropoietin. The increase of erythropoietin concentration in the umbilical cord serum and in the amniotic fluid has been observed in the states of fetus anoxia. This mainly concerns such complications during pregnancy as the fetus hypotrophy, diabetes, serological conflict, and gestosis.
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PMID:[Concentration of erythropoietin in blood serum of the umbilical cord and in amniotic fluid in normal and complicated pregnancies]. 130 56

Because chronic hypoxemia causes a redistribution of iron from serum and storage pools into an expanding erythrocyte mass, and because infants of diabetic mothers are often hypoxemic in utero and have a high prevalence of polycythemia at birth, we studied iron distribution in 43 term infants of diabetic mothers. Twenty-four infants were at an appropriate size for gestational age; 19 were large for gestational age. At birth, 28 infants (65%) had abnormal serum iron profiles; eight had decreased ferritin concentrations only (stage 1), nine had decreased ferritin and increased total iron-binding capacity values (stage 2), and 11 had these serum findings plus elevated free erythrocyte protoporphyrin concentrations (stage 3). The hypoglycemic infants who were large for gestational age (n = 14) had a higher prevalence of abnormal iron profiles than euglycemic infants who were appropriate in size for gestational age (n = 20; 93% vs 50%; p = 0.009). Progressively abnormal iron profiles were associated with higher glycosylated fetal hemoglobin values, greater degrees of macrosomia, increased hemoglobin and erythropoietin concentrations, and increased erythrocyte/storage iron ratios. Erythropoietin concentrations were inversely linearly correlated with serum iron values (n = 32, r = -0.54; p = 0.003). The combined erythrocyte and storage iron pools were significantly lower in infants with abnormal iron values whose mothers were diabetic, particularly in infants of women with confirmed diabetic vasculopathy. We speculate that these findings are likely due to (1) increased fetal iron utilization during compensatory hemoglobin synthesis in response to chronic hypoxemia and (2) reduced iron transfer during late gestation complicated by diabetes.
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PMID:Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. 239 4

The effect of streptozocin (STZ)-induced maternal diabetes in rats on fetal erythropoiesis was studied in short-term cultures of fetal liver cells at the time of switch from embryonic to adult hemoglobins. Liver erythroid cell functions were monitored by measuring the incorporation of [3H]-uridine in trichloroacetic acid (TCA)-soluble and -insoluble cell fractions and of [3H]-leucine in hemoglobin chains. Fetal liver cells of diabetic rats showed a higher incorporation of [3H]-uridine compared with controls when the cells were obtained from 14-day-old fetuses. However, there were no significant differences in the uptake of uridine when cells were obtained from 16-day-old fetuses. In parallel cell cultures, incorporation of [3H]-leucine into adult and embryonic globin chains was studied by separation of the globin chains by high-performance liquid chromatography (HPLC). The overall globin chain synthesis was higher in the fetuses of diabetic mothers compared with controls on day 14 of gestation. Erythropoietin had similar effects on the stimulation of globin chains in the two groups of fetuses. However, in the fetuses of diabetic mothers, erythropoietin had a specific stimulatory effect on embryonic-type globins that was significantly higher in the fetuses of diabetic mothers compared with controls. Differences between fetuses of control and diabetic mothers completely disappeared at 16 days of gestation. It is concluded that maternal diabetes has an effect on the cells synthesizing embryonic hemoglobins on day 14 of gestation, but by the time the switch from embryonic to adult-type hemoglobins is complete, these differences are abolished.
Diabetes 1985 Mar
PMID:Influence of maternal diabetes in rats on hemoglobin synthesis and uridine uptake by fetal liver cells. 388 87

Erythropoietin was administered to five anemic azotemic diabetic subjects for 1 year to assess the effect of increasing red cell mass on clinical well-being and the course of renal functional decline. None of the subjects manifested worsened hypertension or cerebrovascular or cardiovascular complications despite an increase in mean hematocrit from a baseline mean of 29.6% to a mean of 39.5%. The serum creatinine concentration after 1 year of treatment with erythropoietin was 3.7 mg/dL, which was unchanged from the baseline value of 3.5 mg/dL. Plasma viscosity remained constant as red cell mass increased. Although the viscosity of whole blood rose as the hematocrit increased, it was within the range of normal blood viscosity for an equivalent hematocrit. The favorable impact of erythropoietin treatment on three diabetic subjects who had macular edema and anemia is described. One hypothesis to explain the benefit of a raised hematocrit on both diabetic nephropathy and retinopathy is that the metabolic, hormonal, and hemodynamic components of the diabetic syndrome, in concert, produce tissue and cellular hypoxia that is ameliorated in part by the greater oxygen-transporting capacity of a raised red cell mass. The pseudohypoxia of diabetes may be implicated in the pathogenesis of diabetic neuropathy, retinopathy, muscular dysfunction, and nephropathy.
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PMID:Erythropoietin in diabetic macular edema and renal insufficiency. 761 Dec 53

Erythropoietin (EPO) given subcutaneously (SC) once per week has been successful in the treatment of anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. We have identified a population of CAPD patients that requires EPO administration once per week or less often. To determine if specific variables could be identified that would predict which CAPD patients would require infrequent EPO dosing, we reviewed the charts of all our CAPD patients who were receiving EPO as of 1 June 1992. Patients had to have been on CAPD for 3 months and EPO for 3 months to be considered for analysis. We identified 12 patients who required EPO once per week or less frequently (infrequent EPO) and 9 patients who required EPO more than once per week (frequent EPO). Parameters that were analyzed included age, gender, race, time on CAPD, history of gastrointestinal bleeding, exit-site infection or peritonitis in the last 60 days, diabetes, amount of dialysate instilled per day, and the number of exchanges per day. Laboratory data that were analyzed included hemoglobin, hematocrit, serum iron, total iron-binding capacity, ferritin, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, albumin, total protein, parathyroid hormone, and aluminum. Categorical data were analyzed via chi-square, and numerical data were analyzed via the t-test. The infrequent EPO group required only 35% as much EPO as the frequent group to maintain hemoglobin and hematocrit, which were significantly greater. The only parameter that was different between the two groups was age (infrequent EPO 42 +/- 13.2 vs frequent EPO 55.8 +/- 11.9 years, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infrequent dosing of subcutaneous erythropoietin for the treatment of anemia in patients on CAPD. 810 57

The pathogenesis, clinical manifestations, and management of orthostatic hypotension (OH) are reviewed. OH is a decline in blood pressure that occurs when one moves from a lying to a standing position that results in symptoms of cerebral hypoperfusion, most commonly lightheadedness and syncope. The disorder may result from primary autonomic disorders, such as Shy-Drager syndrome; reversible nonautonomic causes, such as reduced blood volume; underlying diseases, such as diabetes mellitus; and drugs. Elderly people are predisposed to OH. The diagnosis of OH is based on the documentation of postural hypotension accompanied by symptoms of cerebral ischemia. The goal of therapy is to relieve symptoms. Nonpharmacologic approaches are preferred and include increasing sodium intake, avoiding rapid postural changes, and wearing elastic garments. OH is difficult to treat pharmacologically because of varying responses and adverse effects. The drug of choice for all types of OH is fludrocortisone acetate, although caution must be used in patients with congestive heart failure. Prostaglandin synthetase inhibitors can also be used for all types of OH but have had more limited success. Sympathomimetics with or without monoamine oxidase inhibitors, beta-adrenergic antagonists, and ergot alkaloids should be administered only to patients with certain types of OH, and patients must be monitored closely. Clonidine, midodrine, yohimbine, octreotide, dopamine antagonists, desmopressin, and epoetin alfa have not been well studied and should be limited to patients with severe, refractory disease. Although no uniformly effective treatment regimen exists, OH can often be adequately managed with a combination of nondrug and drug therapies.
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PMID:Management of orthostatic hypotension. 820 84

Outcomes goals in managing anemia in end-stage renal disease (ESRD) with epoetin alfa and other therapies are illustrated with a case study. Anemia is common in patients with ESRD undergoing hemodialysis; the cause is primarily a reduction in the secretion of erythropoietin. Multiple coexisting factors, such as iron deficiency and blood loss, also contribute. Outcomes goals include decreasing blood transfusions, increasing physical performance, improving cardiovascular and cognitive function, enhancing overall well-being, and achieving self-sufficiency. The potential to achieve these goals has been linked to the attainment of an optima, hematocrit and hemoglobin concentration with epoetin alfa therapy. Once epoetin alfa is begun, safety and effectiveness should be monitored and attainment of outcomes goals assessed. Supplemental iron, folate, and cyanocobalamin may be necessary, as may management of the underlying inflammatory process. The pharmacist can help optimize outcomes by conducting drug-use evaluations, monitoring laboratory test values and drug dosages, assessing drug effectiveness, and counseling patients. A case study of a 67-year-old woman with diabetes mellitus and ESRD who was placed on hemodialysis is presented as an example of how the pharmacist can help optimize outcomes. Opportunities for pharmacists in outcomes management in patients with ESRD-associated anemia include monitoring epoetin alfa therapy, counseling patients, and working with the renal team.
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PMID:Health care outcomes case study: anemia in end-stage renal disease. 884 42

The number of patients with significant chronic renal failure is expanding rapidly in the United States. All physicians and medical-care providers will have an increasingly important role in the detection and management of renal failure in patients who are not undergoing dialysis. Patients with diabetes or hypertension should be carefully monitored for the development of renal insufficiency by using screening tools such as blood pressure measurement, determination of serum creatinine, urinalysis, and determination of 24-hour urinary microalbuminuria. In order to slow the progression of renal disease, attenuate uremic complications, and prepare patients with renal failure for renal replacement therapy, all medical-care providers should "take care of the BEANS." Blood pressure should be maintained in a target range lower than 130/85 mm Hg, and in many patients, angiotensin-converting enzyme inhibitors may be beneficial. Erythropoietin should be used to maintain the hemoglobin level at 10 to 12 g/dL. Access for long-term dialysis should be created when the serum creatinine value increases above 4.0 mg/dL or the glomerular filtration rate declines below 20 mL/min. Nutritional status must be closely monitored in order to avoid protein malnutrition and to initiate dialysis before the patient's nutritional status has deteriorated. Nutritional care also involves correction of acidosis, prevention and treatment of hyperphosphatemia, and administration of vitamin supplements to provide folic acid. Specialty referral to nephrology should occur when the creatinine level increases above 3.0 mg/dL or when the involvement of a nephrologist would be beneficial for ongoing management of the patient.
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PMID:A practical approach to the management of patients with chronic renal failure. 1008 97

The quality of life of patients with end-stage renal disease (ESRD) has become an area of intensive investigation because of the high costs of renal-replacement therapy (dialysis or renal transplantation) and the rising prevalence of renal failure. Studies comparing quality of life of patients using different forms of renal-replacement therapy are flawed by deficiencies in study design, such as lack of randomisation. Nevertheless, in both retrospective and prospective studies, transplantation has been shown to offer the highest levels of functional ability, employment and subjective quality of life. After case-mix adjustment, there is little difference between peritoneal dialysis and haemodialysis in terms of quality-of-life (QOL) outcomes. Vocational rehabilitation is an important aim of therapy; for patients below retirement age, pre-dialysis education and counselling are important in maintaining employment. The elderly comprise the fastest-growing group of dialysis recipients; multiple comorbidities add to functional impairment in these patients. Subjective quality of life remains surprisingly high in many elderly patients, despite poor objective quality of life. The quality of life of patients with diabetes mellitus and ESRD is lower than that of nondiabetic patients with ESRD. For selected patients with insulin-dependent diabetes mellitus, combined renal and pancreatic transplantation offers the advantage of freedom from insulin injections. Unfortunately, available evidence suggests only small improvements in quality of life with combined transplantation versus kidney-only transplantation, probably because many patients have developed multiple diabetic complications by the time of transplantation. Epoetin alfa (erythropoietin) has been shown to improve quality of life in a number of trials. The optimal target haematocrit is a subject of controversy, but on current evidence, a target of 34 to 37% is reasonable. The degree of improvement in quality of life must be balanced against the additional costs of achieving a higher haematocrit. Further study is necessary to clarify the optimal target haematocrit for epoetin alfa therapy, as well as the possible effects of nutritional support, growth hormone in paediatric patients, and combined renal and pancreatic transplantation in improving quality of life.
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PMID:A review of quality of life in chronic renal failure. 1016 67

In patients with cardiovascular disease, partial correction of anaemia with epoetin improves quality of life and exercise capacity, and reduces left ventricular hypertrophy. The currently recommended haemoglobin in these patients is 11-12 g/dl. The optimal haemoglobin in patients with diabetes mellitus does not differ from that in non-diabetic patients; however, haemoglobin should be increased slowly. There is no difference in the recommended haemoglobin between children and adults. However, epoetin sensitivity is lower in children who, therefore, typically need the same absolute dose of epoetin as adults. Epoetin treatment may delay the progression of chronic renal failure (CRF) in paediatric patients. Elderly patients obtain similar benefits from epoetin as younger adults; moreover, there are no differences in the doses of epoetin required or the optimal haemoglobin. There are very few data available on the effects of epoetin in patients with CRF and chronic obstructive pulmonary disease. At present, a haemoglobin of 11 g/dl seems appropriate. In sickle-cell anaemia patients with CRF, a high haemoglobin could precipitate painful crises; consequently, the recommended haemoglobin is the pre-CRF concentration of 6-9 g/dl. There is no convincing evidence of any effect of previous epoetin treatment on the long-term outcome of renal transplantation. In patients with a failing or failed transplant, the required dose of epoetin may be higher than in pre-transplantation patients. In such cases, transplant nephrectomy might be considered.
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PMID:Should anaemia in subtypes of CRF patients be managed differently? 1033 66


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