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 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

Vascular access complications are a continuing source of hospitalization and morbidity in chronic dialysis patients. Several factors have been identified that are associated with complications in patients with native vein and prosthetic bridge arteriovenous graft fistulas. Early failure of native vein arteriovenous fistulas most consistently are related to small blood vessels. It remains unclear whether other comorbid factors play a role in complications of this fistula type. Prosthetic bridge fistulas are frequently placed in the United States and are associated with frequent complications. Factors most consistently associated with higher complication rates are diabetes mellitus, older age, and black race. Antiphospholipid antibody-associated syndromes and erythropoietin therapy have also been suggested as contributing factors. In addition, elevated lipoprotein(a) and hypoalbuminemia have been found to be associated with an increase of prosthetic graft thrombosis in white and Hispanic dialysis patients. This information strongly suggests that fistula complications are multifactorial. An improved understanding of the mechanisms of these associations may aid in the delineation of the pathogenesis and an improvement in the outcome of this important problem.
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PMID:The effect of comorbid conditions on hemodialysis access patency. 761 14

In 29 pregnancies complicated by maternal diabetes mellitus paired samples of umbilical venous blood were obtained at cordocentesis and delivery to investigate the effect of delivery on indices of fetal oxygenation. After delivery by elective Caesarean section the median umbilical venous blood pH was significantly lower than predelivery, however, there was no significant change in the median umbilical venous blood pO2 or plasma erythropoietin concentration. In those delivered after labour the median umbilical venous blood pH and pO2 were significantly lower and the median plasma erythropoietin concentration was significantly higher than predelivery. The data of this study demonstrate that umbilical venous blood pH and pO2 and plasma erythropoietin are influenced by the mode of delivery and results obtained at delivery may not accurately reflect in utero homeostasis.
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PMID:Effect of delivery on fetal erythropoietin and blood gases in pregnancies with maternal diabetes mellitus. 763 34

Patients on dialysis have an age-adjusted death rate 3.5 times that of the general population. The most common cause of death in patients on dialysis is cardiovascular disease. We prospectively followed a cohort of 433 patients in three centers for a mean of 41 months. Mean hemoglobin level at the beginning of dialysis was 8.39 (+/- 1.7) g/dL, and the mean hemoglobin level during follow-up was 8.84 (+/- 1.5) g/dL. Using Cox's regression model, we found that anemia predicted mortality independently of age, diabetes mellitus, cardiac failure, hypoalbuminemia, serum creatinine, mean arterial pressure, or echocardiographic heart disease. The independent relative risk (RR) of mortality was 1.18 per 1.0 g/dL decrease in hemoglobin level. Anemia also independently predicted the de novo occurrence of congestive heart failure when the same covariates were controlled for (RR, 1.49 per 1.0 g/dL decrease). Anemia was also independently predictive of heart failure at the start of dialysis (RR, 1.14 per 1.0 g/dL decrease) and heart failure recurrence (RR, 1.25 per 1.0 g/dL decrease). Left ventricular hypertrophy is present in 75% of patients on dialysis at the start of therapy for end-stage renal disease. It independently predicts mortality. Our prospective cohort study identified increasing age, hypertension, and anemia as risk factors for its development. One controlled study and several uncontrolled studies demonstrated improvement (but not complete regression) of elevated left ventricular mass in patients on dialysis treated with recombinant human erythropoietin (epoetin).
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PMID:Cardiac function and hematocrit level. 770 71

The burden of cardiac disease is high in chronic uremia. Cardiomyopathy results from a combination of cardiac disorders, particularly dilated cardiomyopathy, left ventricular hypertrophy with normal systolic function, and ischemic heart disease. The prognosis for these cardiac disorders is poor. Known potentially reversible risk factors include uremia, anemia, hypertension, smoking, coronary artery disease, hyperparathyroidism, hyperlipoproteinemia, and left ventricular hypertrophy. Randomized controlled clinical trials of interventions that may prevent or ameliorate cardiac disease in dialysis patients are required. These interventions include normalization of hematocrit with erythropoietin compared with partial correction of anemia, increased amount of dialysis compared with that provided by a dialysis prescription of KT/V of 1., control of blood pressure using angiotensin-converting enzyme inhibitors compared with other antihypertensive agents, control of hyperlipidemia, and treatment of diabetes with agents that prevent collagen cross-linking.
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PMID:The management of cardiac disease in chronic uremia. 784 64

In this study we determine the erythropoietin levels and hematocrit in 22 women with preterm labor, 21 with insulin-dependent diabetes, 22 with preeclampsia, and 20 with normal gestation. The erythropoietin level was higher in the preeclamptic group than in the diabetic group compared with the normal and premature groups. There were no hypoxic fetuses. From this study, we found that the mechanism of increased erythropoietin levels in neonates can be different from fetal hypoxia. Further studies are needed on this subject.
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PMID:Erythropoietin umbilical serum levels during labor in women with preeclampsia, diabetes, and preterm labor. 785 36

The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required.
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PMID:Clinical aspects of cardiomyopathy in dialysis patients. 786 86

A number of inherited and acquired serum protein deficiencies including hemophilias A and B, diabetes mellitus, and the erythropoietin-responsive anemias are currently treated with repeated subcutaneous or intravenous infusions of purified or recombinant proteins. The development of an in vivo gene-transfer approach to deliver physiologic levels of recombinant proteins to the systemic circulation would represent a significant advance in the treatment of these disorders. Here we describe the construction of a replication-defective adenovirus (AdEF1hEpo) containing the human erythropoietin (hEpo) cDNA under the transcriptional control of the cellular elongation factor 1 alpha (EF1 alpha) promoter and the 4F2 heavy chain (4F2HC) enhancer. Neonatal CD-1 and adult SCID mice injected once intramuscularly (i.m.) with 10(7) to 10(9) plaque-forming units (pfu) of this virus displayed significant dose-dependent elevations of serum hEpo levels and increased hematocrits, which were stable over the 4-month time course of these experiments. Adenovirus injected i.m. remained localized at the site of injection and there was no evidence of either systemic infection or a localized inflammatory response. These results suggest that i.m. injection of recombinant replication-defective adenovirus vectors may serve as a paradigm for the treatment of human serum protein deficiencies.
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PMID:Stable delivery of physiologic levels of recombinant erythropoietin to the systemic circulation by intramuscular injection of replication-defective adenovirus. 797 1

Vascular access occlusion results in significant morbidity in hemodialysis patients. Age, diabetes, and synthetic grafts (polytetrafluoroethylene [PTFE]) have been associated with vascular access occlusion in univariate analysis. However, the independent risk associated with each of these factors has not been assessed adjusting for confounding among the factors or by other variables, such as blood pressure (BP) or hematocrit. The influence of serum lipoprotein(a) [Lp(a)] and fibronectin on vascular access occlusion has not been widely studied despite their theoretical or demonstrated importance in vascular bypass occlusion. In a cohort study of 124 hemodialysis patients monitored for up to 14 months, we reported that Lp(a) values in the upper tertile (> or = 57 mg/dL) were associated with vascular access occlusion risk in white and Hispanic patients, but not in black patients. We now report an expanded analysis of this data set to determine the independent correlates of vascular access occlusion. Variables tested included age, race, gender, diabetes, access type (PTFE v endogenous), treatment time, systolic BP, hematocrit, heparin and erythropoietin dosage, and serum levels of Lp(a) and fibronectin. In univariate analysis, access occlusion was associated with age, diabetes, PTFE, Lp(a) > or = 57 mg/dL, serum fibronectin, and reduced BP. The independent correlates of first access occlusion were determined with the Cox proportional hazards model. Since the overall model included a significant race x Lp(a) interaction term, we stratified by race. In black patients, risk correlated directly with PTFE (P < 0.01) and inversely with systolic BP (P < 0.001), whereas for white and Hispanic patients, age (P = 0.04) and Lp(a) > or = 57 mg/dL (P = 0.05) were associated with increased risk. In summary, vascular access occlusion was found to be associated with a number of factors. Important independent correlates were PTFE and lower BP in black patients, and age and serum Lp(a) > or = 57 mg/dL in white and Hispanic patients. Diabetes mellitus and increased serum fibronectin may contribute additional risk.
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PMID:Correlates of vascular access occlusion in hemodialysis. 797 20

There has been a gradual increase in the number of diabetic and elderly patients maintained on continuous ambulatory peritoneal dialysis (CAPD) replacement therapy. Eighty randomly selected patients were studied over two years. Weekly normalized urea clearance (KT/Vurea), weekly creatinine clearance/1.73 m2 body surface area (BSA) (Ccr), and protein catabolic rate (PCR) were measured. Selected clinical outcome criteria were assessed. Weekly KT/Vurea was correlated with weekly Ccr (r = 0.538, p < 0.001), and weekly KT/Vurea was correlated with PCR (r = 0.393, p < 0.001). Patients were then stratified according to presence or absence of diabetes mellitus and age > 60 or < or = 60 years. Diabetic and nondiabetic patients had similar weekly KT/Vurea, weekly Ccr, PCR, serum albumin levels, weekly erythropoietin (EPO) requirements, peritonitis rates, and CAPD-related hospitalization rates. The total hospitalization rates, however, were higher in diabetic patients. Elderly and younger patients had similar weekly KT/Vurea, weekly Ccr, PCR, serum albumin levels, and weekly EPO requirements. Elderly patients, however, had higher peritonitis rates and higher total and CAPD-related hospitalization rates.
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PMID:Selected outcome criteria and adequacy of dialysis in diabetic and elderly patients on CAPD therapy. 799 72


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