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)

Nutritional factors and dialysis adequacy are associated with outcome in hemodialyzed patients, but their relative contribution remains controversial, particularly when dialysis adequacy complies with current recommendations (Kt/V >1.2). Survival, clinical, and nutritional data from a cohort of prevalent 1,610 patients treated by hemodialysis in 20 centers in France have been collected over a 2.5-year period, from January 1996 to July 1998. Data including age, sex, cause of end-stage renal disease (ESRD), clinical outcome, time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were analyzed. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) from creatinine generation were computed from pre- and postdialysis urea and creatinine levels. The characteristics of the patients were as follows: age 59.6 +/- 16.5 years, 58.8% males, 11% of diabetics, time on dialysis 63.2 +/- 64.5 m. Weekly dialysis time was 12.18 +/- 1.78 hrs, Kt/V 1.34 +/- 0.34, nPCR 1.10 +/- 0.35 g/kg body weight/day. Albumin concentration was 39.4 +/- 5.3 g/L, prealbumin was 0.33 +/- 0.09 g/L, BMI was 23.0 +/- 4.5 kg/m(2). Overall survival was 89.7% +/- 0.8% and 78.4% +/- 1.1% after 1 and 2 years. In the Cox proportional hazard model, survival was significantly influenced by age, the presence of diabetes, and by concentrations of albumin and prealbumin, but not by other variables, including Kt/V and urea reduction ratio. These results indicate that nutritional protein concentrations were predictive of dialysis outcome, whereas variables reflecting actual body composition and dialysis dose were not. Furthermore, in this well-dialyzed population, dialysis adequacy had no influence on survival. In conclusion, when adequacy targets are met in hemodialyzed patients, survival is mainly dependent on age and nutritional status. Efforts should be focused on the most efficient ways to maintain nutritional status in these patients.
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PMID:Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients. 1115 68

We describe an assay scheme for glucose based on fluorescence resonance energy transfer (FRET) between concanavalin A (con A), labeled with the near-infrared fluorescent protein allophycocyanin (APC) as donor, and dextran labeled with malachite green (MG) as acceptor. Glucose competitively displaces dextran-MG and leads to reduction in FRET, assessed by time-domain fluorescence lifetime measurements using time-correlated single-photon counting. The assay is operative in the glucose concentration range 2.5-30 mM, and therefore suitable for use in monitoring diabetes control. Albumin and serum inhibit FRET but the interference can be prevented by removal of high molecular weight substances by membrane filters. APC shows promise for incorporation in an implanted glucose sensor which can be interrogated from outside the body.
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PMID:Near-infrared fluorescence lifetime assay for serum glucose based on allophycocyanin-labeled concanavalin A. 1135 53

Albumin is the major transport protein in blood and intramolecular movement contributes to this function. Nonenzymatic glycosylation (NEG) of albumin occurs in diabetes and, in this study, fluorometric methods were used to determine the effect of increasing levels of NEG upon intramolecular movement in human serum albumin. Low levels of NEG significantly reduced and left-shifted Trp fluorescence, reduced quenching by acrylamide and inhibited penetration of bis-ANS, while these changes became only modestly more pronounced at higher levels of NEG. Mass spectrometry of tryptic and CNBr NEG-HSA fragments identified potential glycosylation sites and demonstrated only late glycosylation of the C- and N-terminal regions of the protein. Similar changes in diabetes may contribute to altered transport function in these patients.
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PMID:Fluorometric and mass spectrometric analysis of nonenzymatic glycosylated albumin. 1137 74

Pathological changes in the urine sodium dodecyl sulphate gel electrophoresis (SDS PAGE) patterns often precede the occurrence of any sign of renal involvement in diabetes. However, data concerning the most frequent SDS PAGE pattern of the urine in early stages of type I diabetes mellitus are controversial. In the present study an SDS PAGE technique has been used that provides an adequate sensitivity for the detection of the abnormal pattern. Urinary proteins have been analyzed by SDS PAGE in twenty two diabetic adolescents and twenty four age matched controls. Albumin concentration, and N acetyl-beta-D-glucosaminidase (NAG) activity were also measured in the same samples. There was no significant difference in urine albumin concentration and NAG activity between diabetic children and controls. However twelve patients showed an electrophoretic pattern characteristic for glomerulopathy, two had a pattern indicating tubular dysfunction and another two patients had a mixed pattern. Among the twenty four controls only three showed abnormal electrophoretic patterns. The results support the view that early stages of diabetic nephropathy may involve both glomerular and tubular dysfunction. However the exact clinical and prognostic significance of the information provided by SDS PAGE analysis remains to be elucidated.
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PMID:Electrophoretic analysis of urinary proteins in diabetic adolescents. 1143 99

Hypoalbuminemia is the strongest predictor of death in patients with renal failure. We planned to investigate the factors influencing serum albumin levels in continuous ambulatory peritoneal dialysis (CAPD) patients. We prospectively followed 100 CAPD patients for 18.6 +/- 12.8 months. The parameters searched for a correlation with serum albumin levels were: peritoneal transport kinetics; presence of nephrotic syndrome; biochemical parameters; anthropometric measurements; and subjective global assessment (SGA). Older patients (age > or = 60 years), patients with diabetes mellitus or amyloidosis, high and high-average transporters, and those with nephrotic syndrome had significantly lower albumin levels throughout the follow-up. In addition, significantly lower albumin levels were found in patients who were in the SGA "malnourished" categories and those who had iPTH levels < or = 65 pg/mL. Albumin level was negatively correlated with age, C-reactive protein (CRP), and fibrinogen level; it was positively correlated with total cholesterol, intact parathyroid hormone (iPTH) level, and triceps skin-fold thickness. By regression analysis, age [risk ratio (RR): 0.2437], presence of diabetes mellitus (RR: 0.1421) and high or high-average transport status (RR: 0.1156) were independent predictors of hypoalbuminemia (< or = 3.5 g/dL). In conclusion, development of hypoalbuminemia is multifactorial in CAPD patients. Older age, cause of renal failure, transport status, chronic inflammation, presence of nephrotic syndrome, and nutrition status are important determinants of hypoalbuminemia.
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PMID:Predictors of serum albumin level in patients receiving continuous ambulatory peritoneal dialysis. 1151 Feb 78

The aim of this study is to investigate the role of the proximal tubule in microalbuminuria in the early stage of diabetic nephropathy. Diabetes was induced in male Sprague-Dawley rats by an injection of streptozotocin (50 mg/kg, i.v.). After 2 weeks, albumin delivery in the proximal tubule was measured using micropuncture and the endocytosis process of FITC-labeled albumin was evaluated with immunoelectron microscopy. Albumin was significantly reabsorbed in the proximal convoluted tubule (PCT) of controls (0.39+/-0.05 ng/min at early PCT to 0.17+/-0.08 at late PCT, P<0.05), whereas albumin reabsorption was inhibited in diabetic rats (0.27+/-0.05 to 0.21+/-0.08). Immunogold study revealed that FITC-albumin was significantly less reabsorbed in endosomes and lysosomes of S1 segments in diabetic rats than in controls (endosome: 1.20+/-0.10 vs 2.16+/-0.15 microm-1, P<0.0001; lysosome: 0.26+/-0.03 vs 0.83+/-0.07, P<0.0001). The expression of megalin, an endocytosis receptor, was decreased at the apical membrane of PCT in diabetic rats. The lipid peroxidation production in the proximal tubule was significantly increased in diabetic rats. In conclusion, albuminuria in early-stage diabetic rats can be partly explained by a decreased albumin endocytosis with reduced megalin expression and with increased lipid peroxidation in the proximal tubule.
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PMID:Reduced albumin reabsorption in the proximal tubule of early-stage diabetic rats. 1168 57

Cigarette smoking is a risk factor for diabetic nephropathy in Type 1 diabetes (T1DM); a few reports support this possibility in Type 2 diabetes (T2DM) as well. Since heterogeneity among populations could exist, we investigated the association of cigarette smoking and nephropathy, and progression of nephropathy in Italian T2DM patients. A retrospective study was conducted in 273 long-duration T2DM subjects with a 3-year follow-up in the out-patient clinic, and at least one access per year. Albumin excretion rate, serum creatinine, and a number of other parameters implicated in the development of diabetic renal disease were evaluated. Progression of nephropathy was defined as the passage from different stages of renal involvement (no renal derangement, microalbuminuria, proteinuric disease or severe nephropathy). At baseline, 13.2% of the subjects had microalbuminuria, and 3.7% proteinuric disease. Microalbuminuria and proteinuric disease were more frequent in actual smokers than in non- and former smokers (chi2=8.35; p=0.015). Progression of nephropathy was less common in non- and former smokers than in smokers (31 of 134, 23%, and 15 of 67, 22%, and 30 of 72, 42%, respectively; chi2=9.32;p=0.009). From logistic regression analysis, smoking (p=0.0012) emerged as the most important factor associated with progression of nephropathy, followed by packyears (p=0.011), HbA1c mean value at follow-up (p=0.024), and total cholesterol (p=0.038). In conclusion, cigarette smoking is a risk factor for progression of nephropathy also in Italian T2DM patients; reducing or quitting smoking should be part of the therapy or of the preventive measures in these patients and their relatives.
Diabetes Nutr Metab 2001 Dec
PMID:Cigarette smoking is a risk factor for nephropathy and its progression in type 2 diabetes mellitus. 1185 66

The severe diabetic nephropathy that develops in the hypertensive transgenic (mRen-2)27 rat with streptozotocin (STZ) diabetes has previously been considered angiotensin II-dependent. Because metabolic pathways are also activated in the diabetic kidney, the present study aimed to determine whether renoprotection could be afforded with inhibitors of advanced glycation end products (AGEs), ALT-946, and aminoguanidine (AG). At 6 weeks of age, nondiabetic control and STZ diabetic Ren-2 rats were randomized to receive vehicle, ALT-946 (1 g/l), or AG (1 g/l) and were studied for 12 weeks. Systolic blood pressure was unchanged with diabetes, ALT-946, or AG. Both kidney weight and glomerular filtration rate were increased with diabetes and unchanged with ALT-946 or AG. ALT-946 and AG equally ameliorated glomerulosclerosis and medullary pathology; however, ALT-946 did reduce cortical tubular degeneration to a greater extent than AG. Albumin excretion rate, which was elevated with diabetes, was reduced with ALT-946 but not AG. AGE immunolabeling was increased in glomeruli and reduced with ALT-946 and AG. These findings indicate that even in the context of renal injury presumed to be primarily blood pressure- and/or angiotensin II-dependent, approaches that interfere with metabolic pathways such as inhibitors of AGE formation can confer renal protection in experimental diabetes.
Diabetes 2002 Nov
PMID:ALT-946 and aminoguanidine, inhibitors of advanced glycation, improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat. 1240 20

Albumin modified by Amadori glucose adducts has been shown to modulate signal transduction and induce alterations in renal glomerular cells that contribute to the development of diabetic nephropathy. However, the participation of this nonenzymatically glycated protein in the pathobiology of atherosclerotic cardiovascular disease in diabetes has not been established. To probe this issue, we used macrophage RAW cells to assess the effects of glycated albumin on molecular events implicated in the pathogenesis of diabetes-related vascular complications. RAW cells were cultured in medium containing 5.5 mmol/L glucose and glycated or nonglycated albumin, with and without the addition of PD98059, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK), followed by analysis of phosphorylated ERK and the nuclear translocation of nuclear factor (NF)-kappa B and measurement of cellular content of thiobarbituric acid-reactive substances and the concentration of transforming growth factor (TGF)-beta(1) in the spent medium. We demonstrate, for the first time, that glycated albumin activates RAW cell ERK and promotes ERK-dependent increases in TGF-beta(1) production, oxidative stress, and NF-kappa B activation. Preincubation with the antioxidant alpha-lipoic acid partially prevented the glycated albumin-induced increase in NF-kappa B activation. These findings indicate that Amadori-modified glycated albumin modulates macrophage cell biology independent of high glucose concentration. The effects of glycated albumin on RAW cell molecular mediators and cytokine production may have pathophysiologic significance with respect to the accelerated atherosclerosis that occurs in diabetes.
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PMID:Glycated albumin increases oxidative stress, activates NF-kappa B and extracellular signal-regulated kinase (ERK), and stimulates ERK-dependent transforming growth factor-beta 1 production in macrophage RAW cells. 1267 69

Albumin concentrations persistently between 20 and 200 mg/L in first morning spot urine or urine collected overnight, referred to as microalbuminuria, indicate incipient nephropathy in diabetes mellitus. This study validates a new point-of-care device, the HemoCue Urine Albumin analyser, for handling, accuracy precision and predictive values (PV+/-) at 20 mg/L. Over a period of 2 months, 200 microalbuminuria samples were selected at the Department of Clinical Chemistry according to the results from the Integra 700 instrument (Roche, R) and analysed on the same day using the HemoCue analyser (HemoCue, H) and the Immage instrument (Beckman, B), in all cases closely following the manufacturers' instructions. Only 137 results were within the measuring range of H, 10-150 mg/L. Comparisons yielded regression lines H=1.06R-7.2 (r2=0.94), H=1.08B-3.1 (r2=0.94) and R=1.00B+4.3 (r2=0.99). Inter-assay (n=24) CV% at 12 mg/L was H=18.2, R=4.2 and B=2.9 and at 65 mg/L: H=6.1, R=1.8 and B=2.6. Intra-assay duplicate CV% for H at 21-40 mg/L was 13.2, at 41-80 mg/L 10.8 and at 81-150 mg/L 9.2. Intra-assay repeatability (n=8) CV% at 28 mg/L was 7.2-13.8, at 57 mg/L 6.4-8.4 and at 105 mg/L 4.3-7.1. External quality assurance urine albumin (B) was +5.7% cf. nephelometry and (R) +1.0% cf. turbidimetry (n=6) method-group means. PV+/- values were (H versus R) 0.98/0.37 and (H versus B) 0.95/0.65. HemoCue is easy to handle. Results below 20 mg/L need to be confirmed at the central laboratory to exclude microalbuminuria. Values above 20 mg/L can be used to follow microalbuminuria, as precision allows discerning steps of 10 mg/L.
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PMID:Validation of albumin determined in urine with the HemoCue point-of-care analyser. 1275 93


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