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Query: UMLS:C0011849 (diabetes)
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The effects of glycation of either albumin, a plasma protein, or GBM were examined in an in vitro model of GBM permeability. Albumin was incubated with glucose in vitro, and nonglycated and glycated albumin were separated by affinity chromatography. Rat GBM was glycated either in vivo after the induction of diabetes or in vitro after incubation with 25 mM glucose. 150 micrograms of GBM was consolidated in an ultrafiltration cell, and albumin permeability across the GBM filter was assessed at an applied pressure (50 mmHg) selected to approximate glomerular capillary pressure in vivo. The sieving coefficient of glycated albumin was greater than the sieving coefficient of nonglycated albumin (0.25 +/- 0.03 vs. 0.10 +/- 0.02; P < 0.05). GBM glycated in vivo in diabetic rats exhibited native albumin and water permeability that was indistinguishable from that for GBM from control rats. Similarly, GBM glycated in vitro by incubation with 25 mM glucose exhibited water and albumin permeability identical to that for GBM incubated in buffer. Thus, the glycation of albumin, but not of GBM, leads to enhanced permeability in an in vitro GBM filtration system. Increased permeability of glycated albumin may contribute to albuminuria and/or renal injury in states of increased circulating glycated albumin such as diabetes and experimental galactosemia.
Diabetes 1992 Nov
PMID:Glycation of albumin, not glomerular basement membrane, alters permeability in an in vitro model. 139 17

Glycated hemoglobin (GHb), fructosamine and glycated albumin (GA) in hemolytic sera from cadavers were analyzed for the postmortem diagnosis of diabetes mellitus. The levels of GHb and fructosamine were determined by boronate affinity chromatography and colorimetry, respectively. Albumin fraction was isolated from the samples by Affi-Gel Blue affinity chromatography. The glycated and non-glycated molecules were separated by boronate affinity chromatography, and quantitated by bromcresol green method. Fructosamine could not be analyzed from highly hemolytic sera containing more than 10 g/l hemoglobin. In such samples, the levels of GHb and GA were deviated from the standard values, indicating their postmortem degradation. In less hemolytic samples, GA was as informative as GHb and fructosamine for the diagnosis of diabetes mellitus.
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PMID:Analysis of glycated albumin in postmortem blood samples as the diagnostic parameters of diabetes mellitus. 140 16

Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose.
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PMID:The relationship between long-term glycaemic control and diabetic nephropathy. 143 68

Albumin excretion rate, glomerular filtration rate (GFR) and kidney volume in obese patients and normal-weight controls were compared with body mass index (weight (kg)/height2 (m)) in 17 subjects. Body mass index varied from 21.5 to 48.0, the albumin excretion rate from 2.8 to 17.8 micrograms/min, and the kidney volume from 238 to 468 ml. Body mass index correlated significantly with albumin excretion rate and with kidney volume (p < 0.01), but not with the GFR. Neither the body mass index nor the albumin excretion rate showed any correlation with blood pressure. Albumin excretion rate in obese subjects could be as good an early predictor of complications as it is in patients with diabetes mellitus, and in the elderly.
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PMID:Microalbuminuria in obesity. 143 3

We studied the relationship between albuminuria (measured as albumin/creatinine ratio (alb/Cr) in a random urine sample) and measures of glycaemic control (fructosamine, HbA1 and glucose) in 470 patients with non-insulin-dependent diabetes mellitus (NIDDM). Albumin excretion was in the microalbuminuric range (alb/Cr ratio > 5.4-40.3) in 112 (23.8%) and in the macroalbuminuric range (alb/Cr ratio > 40.3 mg/mmol) in 89 patients (18.9%). Fourteen percent (n = 67) of patients had a normal plasma HbA1 (< or = 8.5%) while 27% (n = 127) had a normal plasma fructosamine concentration (< or = 2.2 mmol/l). Using stepwise multiple regression analysis, plasma fructosamine concentration was found to be independently and negatively associated with urine albumin/creatinine ratio (B = 0.24, P < 0.006) in the macroalbuminuric group. Further analysis of the relationship between plasma albumin concentration and indices of glycaemic control showed that plasma albumin concentration correlated negatively with random plasma glucose concentration in the normoalbuminuric patients (r = -0.16, P = 0.008) but not in microalbuminuric or macroalbuminuric groups. HbA1 was not correlated with plasma albumin concentration. Our results indicate that albuminuria has an effect on the plasma fructosamine concentration which is independent of plasma albumin concentration.
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PMID:The inter-relationships between albuminuria, plasma albumin concentration and indices of glycaemic control in non-insulin-dependent diabetes mellitus. 146 40

Micro-albuminuria is a very sensitive predictor of the development of renal disease in insulin- and non-insulin-dependent diabetes mellitus. A reliable dipstick test for routine screening for micro-albuminuria is, therefore, desirable. Such a test has been developed by Boehringer Mannheim, Germany, and marketed as Micral-Test. It is an immunological slide-test with semi-quantitative properties. To evaluate its performance as a screening test we compared it with a turbidimetric immuno-assay. In 396 urine specimens from 132 patients, sensitivity was 91% and specificity 96% for a discriminating albumin level of 20 mg/l. Correlation with quantitative values was reasonable (r = 0.73). We also tested for micro-albuminuria, defined as mean albumin excretion rate of > or = 20 micrograms/min, determined with the turbidimetric immuno-assay in timed overnight urines on three consecutive days, whereas Micral-Test was considered to be positive for micro-albuminuria if the albumin concentration in one of the three urine samples was > or = 20 mg/ml. In 132 patients, the sensitivity of Micral-Test was 82% and the specificity 86%. Albumin excretion rate in all false-negative results was < 50 micrograms/min. We therefore concluded that Micral-Test is a useful qualitative screening test for micro-albuminuria in diabetic patients.
Diabetes Res Clin Pract 1992 Nov
PMID:Micral-Test: a qualitative dipstick test for micro-albuminuria. 147 56

The effects of aldose reductase inhibition on kidney function were studied in rats with streptozotocin-induced diabetes mellitus. Diabetic rats were fed sorbinil (20 and 50 mg/kg) by daily gastric gavage and were compared with untreated diabetic rats and normal rats. The rats were under daily supervision with regard to blood glucose control, insulin administration and body weight. The aim was to promote continuous body growth and to maintain the blood glucose concentration at around 22 mmol/l without large day-to-day fluctuations. The renal functional changes observed in this well-established diabetic model closely resembled those reported in human Type 1 (insulin-dependent) diabetes mellitus. Sorbinil treatment completely prevented renal cortical sorbital accumulation, but did not abolish kidney enlargement or the increase in ultrafiltration pressure and glomerular filtration rate. Albumin excretion was increased to the same extent in the sorbinil-treated and in the untreated diabetic rats. We conclude that increased metabolism of glucose to sorbitol does not cause the hyperfiltration in rats with streptozotocin-induced diabetes.
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PMID:Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats. 152 21

In insulin-dependent diabetes (IDDM), an overactivity of sodium-lithium countertransport (Na+/Li+ CT) has been associated with the risk of nephropathy and hypertension, two conditions of insulin resistance. We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). The two groups were similar in age (mean +/- SE 36 +/- 2 vs. 33 +/- 1 yr), duration of diabetes (19 +/- 3 vs. 18 +/- 2 yr), body mass index (26 +/- 0.8 vs. 24 +/- 0.6 kg/m2), arterial blood pressure (systolic/diastolic 121 +/- 4/79 +/- 2 vs. 122 +/- 3/77 +/- 2 mmHg), and glycemic control (HbA1 8.5 +/- 0.4 vs. 8.0 +/- 0.4%). Albumin excretion rate (AER) ranged between 4.7 and 148 (geometric mean 14) micrograms/min in group 1 and between 2.7 and 93 (geometric mean 11) micrograms/min in group 2. There were four microalbuminuric patients (AER greater than 30 micrograms/min) in each group. Whole-body glucose uptake was significantly reduced on average in group 1 compared with group 2 (41.6 +/- 2.2 mumol.kg-1.min-1 [7.48 +/- 0.4 mg.kg-1.min-1] vs. 49.6 +/- 2.2 mumol.kg-1.min-1 [8.93 +/- 0.4 mg.kg-1.min-1, P = 0.03), but some overlap existed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 May
PMID:Sodium-lithium countertransport activity and insulin resistance in normotensive IDDM patients. 153 93

A timed urine collection is necessary to determine the excretion rate of albumin (AER) but such specimens are tedious to collect and frequently inaccurate. Albumin excretion can also be quantified by the use of the albumin:creatinine ratio in randomly obtained specimens. In the present study the agreement between AER as measured on a 24-h urine collection and as estimated from the albumin:creatinine ratio is determined. Previously published studies have examined the correlation rather than the agreement between these methods and not taken into account the biological variability of AER. Thirty patients with diabetes who had normal renal function, but varying degrees of albuminuria, produced two 24-h specimens and two random daytime specimens of urine. AER was measured on the former and estimated from the latter by multiplying the albumin:creatinine ratio by an estimate of that individual's creatinine excretion rate. Agreement between the methods and the biological variability was determined by using appropriate statistical methodology, the main outcome measure being the limits of agreement between repeat values for both measurements and both estimates of AER, and between the averages of the measurements and the estimates. The limits of agreement between repeated 24-h measurements were wide, the second specimen being 33 to 490% of the first. The estimates of AER gave values numerically similar to the measurements. The limits of agreement between the two estimates did not differ significantly from those of the measurements, nor did the limits of agreement when the average of the measurements and the average of the estimates were compared (all NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measuring the albumin excretion rate: agreement between methods and biological variability. 156 48

In metabolic disorders such as diabetes mellitus (DM) and obesity, renal abnormalities may also occur even when renal dysfunction is not be detected by conventional urinalysis. By use of immunological technique, an investigation was made on the subclinical abnormality in the excretion of urinary proteins in DM and obese (OB) subjects. Urinary excretion of the proteins (albumin, IgG, IgG4, beta 2-microglobulin) and fractional clearances (clearance ratios to creatinine clearance) at sitting position were respectively measured. Albumin excretion rate (AER) and fractional albumin clearance were higher in DM and OB than normal controls (NC). In non-diabetic subjects (OB+NC), body mass index (BMI) significantly positively correlated with AER and fractional albumin clearance. In DM, not only AER and fractional albumin clearance but also IgG4 excretion rate and fractional IgG4 clearance positively correlated with BMI. In DM with BMI less than 22 Kg/m2, HbA1C significantly correlated with AER, IgG4 excretion rate, and fractional albumin and IgG4 clearances. The data suggest that microproteinuria in DM and OB may be of glomerular origin. In DM, in the light of an increase in urinary excretion of negatively charged IgG4, it is also suggested that proteinuria is attributed to the alteration of charge barrier as well as to that of glomerular hemodynamics. Lastly but not least , obesity-related factor should also be taken into account in the development of microalbuminuria of the diabetic patient.
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PMID:[A study on microproteinuria among diabetic and obese subjects without clinically overt proteinuria]. 158 64


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