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)

We determined the urinary excretion, expressed as the protein/creatinine ratio (morning urines), of albumin (a marker of glomerular dysfunction) and retinol-binding protein (RBP; a low-molecular-mass protein marker of tubular proteinuria) in 102 non-insulin-dependent diabetic patients. There was a statistically significant (P < 0.0001) correlation (rho = 0.38) between the urinary excretion values of the two proteins. The population could be divided into four subgroups: 32 with normal excretion values, 15 with above-normal urinary excretion of RBP, 24 with above-normal urinary excretion of albumin, and 31 patients with above-normal urinary excretion of both proteins. No patients had above-normal serum creatinine concentrations or above-normal serum RBP concentrations. This seems to exclude "tubular overflow proteinuria" as the cause of the increased urinary excretion of RBP seen in some patients with non-insulin-dependent diabetes. Our data suggest the presence of a state of proximal tubular dysfunction in these patients.
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PMID:Low-molecular-mass proteinuria as a marker of proximal renal tubular dysfunction in normo- and microalbuminuric non-insulin-dependent diabetic subjects. 844 68

1. It has been suggested that tubular damage may precede glomerular damage at the onset of diabetic nephropathy. This may be reflected by increased urinary excretion of low-molecular-mass proteins, such as retinol-binding protein. 2. We have measured the urinary excretion rate of retinol-binding protein overnight, during orthostasis and during a hyperinsulinaemic euglycaemic clamp (blood glucose concentration 7.0 mmol/l) with stable diuresis in 34 normotensive, normoalbuminuric insulin-dependent diabetic patients and in 10 normal control subjects. Normal control subjects were not clamped. A further four normoalbuminuric insulin-dependent diabetic patients were rendered euglycaemic without a water load. 3. Overnight retinol-binding protein excretion rate was 58 (16-157) [median(range)] ng/min in patients with insulin-dependent diabetes and 32 (15-72) ng/min in control subjects (P < 0.01). The excretion rate did not change during orthostasis [patients with insulin-dependent diabetes, 67 (3-173) ng/min; control subjects, 23 (5-78) ng/min]. During the euglycaemic clamp retinol-binding protein excretion rate increased to 383 (78-4897) ng/min in patients with insulin-dependent diabetes (P < 0.01). An average increment in retinol-binding protein excretion rate of greater than 4000% was noted after acute euglycaemia in those patients with insulin-dependent diabetes who were not water-loaded. 4. In insulin-dependent diabetes, both overnight and orthostatic retinal-binding protein excretion was not correlated with fasting blood glucose concentration, HbA1, fructosamine or duration of diabetes. The absolute and incremental excretion rates of retinol-binding protein during the clamp were, however, correlated with both fasting blood glucose concentration and glucose excretion rate (rs = 0.41-0.48, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of posture and acute glycaemic control on the excretion of retinol-binding protein in normoalbuminuric insulin-dependent diabetic patients. 848 50

Urinary excretion of five low molecular weight proteins (LMWP) [beta 2-microglobulin (beta 2m), cystatin C (cyst C), Clara cell protein (CC16), retinol-binding protein (RBP) and alpha 1-microglobulin (alpha 1m)], albumin and N-acetyl-beta-D-glucosaminidase (NAG) were quantified in 16 patients who followed a weight reduction program which included Chinese herbs, which have been incriminated in the genesis of Chinese herbs nephropathy (CHN). An additional group of four patients transplanted for CHN were investigated. Urinary data were obtained for comparison purpose in five groups of proteinuric patients: two groups with normal serum creatinine (SCr) and glomerular albuminura [12 patients with diabetes mellitus and microalbuminuria (DN), 10 patients with primary nephrotic syndrome (NS)]; two groups with normal SCr and toxic nephropathy [6 patients with analgesic (AN), 9 patients with cadmium nephropathy (CdN)]; and one group of seven patients with glomerular diseases and increased SCr (GN). Patients were classified according to serum level S beta 2m to take into account the possibility of overflow proteinuria at S beta 2m > or = 5 mg/liter. Three patients (CHN0) with a S beta 2m < 5 mg/liter, had a normal urinary protein pattern including NAG and a normal S beta 2m. Eight patients (CHN1) with a S beta 2m < 5 mg/liter had various abnormalities of their urinary protein pattern. In four of them (CHN1a) only beta 2m, RBP and CC16 were increased while total proteinuria and SCr were normal. In the other four (CHN1b and c) albumin, cyst C, alpha 1m and NAG were also elevated, while total proteinuria and SCr were moderately raised. Five patients (CHN2) with a S beta 2m > or = 5 mg/liter had a markedly increased excretion of all LMWP, albumin and NAG (CHN1 vs. CHN2, P < 0.05) as well as a further increase in total proteinuria and SCr. The urinary LMWP/albumin concentration ratio was strikingly higher in CHN patients than in patients with glomerular albuminuria (CHN1 vs. DN and NS, P < 0.01) or moderate renal failure with elevated S beta 2m level (CHN2 vs. GN, P < 0.01), confirming the existence of a tubular proteinuria independent of glomerular albuminuria or overflow proteinuria. A similar proteinuria pattern was present in the two toxic nephropathies (CdN and AN). This pattern was no longer recognizable after transplantation. In conclusion, CHN exhibits various profiles of tubular proteinuria which are the hallmarks of the disease. This pattern is still detectable in patients with renal failure and/or glomerular albuminuria. It is identical to that observed in cadmium and analgesic nephropathies. It does not recur after transplantation. Its most sensitive and reliable marker is a raised urinary level of CC16 or RBP.
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PMID:Low molecular weight proteinuria in Chinese herbs nephropathy. 854 16

In an in-depth examination to better define the renal effects of mild hypertension, we used urinary proteins to indicate damage to the glomerulus (albumin), tubular reabsorption capability (retinol-binding protein), and turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) in a group of 18 people with mild hypertension not associated with diabetes and a control group (n = 12). The participants' activity was controlled on a high normal salt diet for 3 days followed by a low salt diet for 4 days. Two distinct patterns of albumin excretion were evident in the hypertensive group: 22% had elevated, highly variable excretion patterns, and the rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or 16 mg/L, with the lowest within-person biological variability given by albumin calculated as a ratio to creatinine. Albumin and NAG excretion primarily correlated with systolic blood pressure and the best correlations were given by ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8 mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg), diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group with mild hypertension. However, albumin excretion did not decrease when dietary salt content was lowered. The group with hypertension also had higher urinary excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in the group had a higher excretion of retinol-binding protein than did whites in the control group (P < .02). Retinol-binding protein values, however, were within the normal range, indicating that the elevated albumin values were the result of changes in selectivity of the glomerulus.
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PMID:An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension. 855 30

We studied 24-h ambulatory blood pressure (SBP, DBP), actual glycemic control assessed from seven blood glucose measurements, 16-h daytime and 8-h nighttime urinary excretion of albumin (UAE) and retinol-binding protein (URBP) in 20 normoalbuminuric (group A, nighttime UAE < 20 micrograms/min) and 20 microalbuminuric and low-proteinuric type I diabetic patients (group B, nighttime UAE 20-500 micrograms/min) matched for age and diabetes duration. Glycemic control was similar in the two groups. Daytime and nighttime SBP and DBP were higher in group B compared to group A (p < 0.01). Nighttime decrease in SBP and DBP correlated with nighttime decrease in UAE in group B (p < 0.05, p < 0.001), but not in group A. There was no correlation between BP and actual glycemic control in either group. We found higher daytime and nighttime URBP in group B compared to group A (p < 0.05). We conclude that, in microalbuminuric and low-proteinuric patients, daytime and nighttime BP was elevated but still in the normal or borderline range, and nighttime decrease in BP correlated with nighttime decrease in UAE but not with actual glycemic control. Increased URBP in these patients suggests slightly impaired proximal tubular function in early stages of diabetic nephropathy.
J Diabetes Complications
PMID:24-h ambulatory blood pressure, daytime and nighttime urinary albumin and retinol-binding protein excretion in type I diabetic patients. 857 35

We studied 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), 16-h daytime and 8-h nighttime urinary excretion of albumin (UAE) and retinol-binding protein (URBP) in 20 type 1 diabetic patients (group 1) with normoalbuminuria (UAE < 20 micrograms/min) and 20 type 1 diabetic patients (group 2) with microalbuminuria and low proteinuria (UAE 20-500 micrograms/min). The groups were comparable in age, diabetes duration and actual glycaemic control. Daytime and nighttime SBP and DBP were higher in group 2 compared to group 1 (p < 0.01). Nighttime decrease in SBP and DBP correlated with nighttime decrease in UAE in group 2 (p < 0.05, p < 0.001). There was no correlation between BP and actual glycemic control in either group. Daytime UAE was found in group 2 by 20% higher than nighttime UAE. We found higher daytime and nighttime URBP in group 2 compared to group 1 (p < 0.05). We conclude, that microalbuminuric and low-proteinuric patients had elevated BP and nighttime decrease in BP correlated with nighttime decrease in UAE but not with actual glycemic control. Increased URBP in these patients suggests impaired proximal renal tubular function in early stages of diabetic nephropathy.
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PMID:[Diurnal changes in blood pressure, albuminuria and urinary excretion of retinol-binding protein in type I diabetics]. 862 57

In most cases of glomerulonephritis (GN) long-term course lead to chronic renal failure. The cause of inevitably gradually progress of GN to end-stage renal disease (ESRD) is unclear. The histological abnormalities seen in patients with progressive renal failure consist of focal and segmental glomerulosclerosis and tubulointerstitial nephritis. At present it is considered that tubulointerstitial changes attends almost all forms of progressive glomerular and vascular injury. It was known that chronic tubulointerstitial nephritis is characterized morphologically by tubular atrophy, interstitial fibrosis and interstitial inflammation of variable severity. The pathomechanism of this changes is complicated. Tubular ischaemia results from obliteration of peritubular capillaries, adaptation of tubular function with increased oxygen consumption and increased glomerular capillary permeability to macromolecules are reasons of chronic tubular damage. Injured tubules release growth factors and cytokines, which induce interstitial fibroblast proliferation, chemo-attraction and proliferation of infiltrating cells, and disruption of the balance between synthesis and degradation of cellular constituents. The consequences of these processes are tubular atrophy and interstitial fibrosis. Because of many studies concurred that tubulointerstitial changes determinant the progression of GN, tubular injury markers were searched for. Although over 50 enzymes were detected in human urine, only a few have been used for diagnosis in renal disease. The most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal injury too. Pathological value of GGT was observed even in the early stage of disease. Measurement of urinary excretion of low molecular weight proteins was valuable supplement in estimation of tubulointerstitial system malfunction. These proteins are readily filtered by normal glomeruli and virtually completely reabsorbed by normal proximal tubules. Favour are alpha-1-microglobulin (alpha-1-m) and retinol-binding protein (RBP) because they are less affected than beta-2-microglobulin (beta-2-m) by low urine pH. Above presented review confirm that further research in correlation between activity of disease, histological picture, deterioration in renal function and changes in urinary excretion of markers proteins (for example alpha-1-m, AAP, NAG, GGT) is advisable, and can contribute to use in clinic diagnostics of GN.
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PMID:[The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis (GN)]. 875 11

We aimed to examine the relationship of serum lipids, lipoproteins, apolipoproteins and antioxidants with renal dysfunction as measured by urinary excretion of albumin and of retinol binding protein (RBP) in insulin-dependent diabetes mellitus (IDDM). We studied 121 patients with IDDM. Glomerular function was assessed as the urinary albumin/creatinine ratio (UA/UC), and tubular function as the urinary retinol-binding protein/creatinine ratio (UR/UC), both measured in three early morning spot urine samples. The mean (range) UA/UC was 1.95 mg/mmol (0.3-476.5) and UR/UC was 17.5 micrograms/mmol (1.0-1853.8). 17% of the patients had a UA/UC > 3 mg/mmol and 33% had a UR/UC > 20 micrograms/mmol. Significant positive correlations were observed between both UA/UC and UR/UC and the following: serum total cholesterol (P < 0.005); triglycerides (P < 0.001); apolipoproteins A-I (P < 0.05), A-II (P < 0.02) and B (P < 0.002); glycated haemoglobin (P < 0.002). No significant associations were found with serum vitamin E, beta-carotene or total antioxidant activity. In multiple regression, only UA/UC was independently associated with serum apo B and cholesterol concentrations. In conclusion, in IDDM glomerular dysfunction, as measured by UA/UC, is associated with elevated serum cholesterol, triglycerides, apo B, apo A-I and apo A-II, but not with HDL cholesterol or antioxidant status. Tubular dysfunction tends to occur with increasing albuminuria, but it is not independently associated with serum lipid, lipoprotein, apolipoprotein or antioxidant levels.
Diabetes Res Clin Pract 1996 Apr
PMID:Lipids, lipoproteins, antioxidants and glomerular and tubular dysfunction in type 1 diabetes. 880 85

Decreased plasma concentrations of vitamin A (retinol) and retinol-binding protein have been previously identified in human subjects with type I diabetes mellitus. The present study was undertaken to investigate the effects of streptozotocin-induced diabetes in rats of three different strains including Wistar Furth, Sprague Dawley and Wistar, on plasma and liver concentrations of vitamin A. The diabetic animals gained less weight than nondiabetic controls even though they ate 50% more food. The hepatic vitamin A concentration was increased at three weeks after the onset of diabetes in all three strains of rats but the magnitude of increase was greater in Wistar than either Wistar Furth or Sprague Dawley rats. This increased storage of vitamin A in diabetic animals most likely is due to increased food intake. The plasma concentrations of vitamin A, on the other hand, remained unaffected in Wistar Furth and decreased moderately (P < 0.02) in Sprague Dawley but severely (P < 0.0001) in Wistar rats. The fact that the plasma vitamin A levels in diabetic Wistar and Sprague Dawley rats were markedly reduced despite their increased hepatic store suggest an impairment in the transport of vitamin A from the liver. The circulatory levels of vitamin A in Wistar rats are more sensitive to the diabetic state, which is in agreement with those observations seen in diabetic patients. Because of this similarity, it is reasonable to suggest that Wistar should be the choice of rat strain for future experimental studies involving vitamin A and diabetes relationships.
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PMID:Strain variation in vitamin A (retinol) status of streptozotocin-induced diabetic rats. 884 83

The aim of this study was to assess the relationship between markers of tubular function, markers of glycaemic control and erythrocyte sodium-lithium countertransport activity (SLC) in 40 normotensive, normoalbuminuric insulin-dependent diabetic (IDDM) subjects and 11 normal control subjects. Nine IDDM subjects had SLC > 0.40 mmol lithium h-1 litre RBC-1. Glomerular filtration rate (GFR) and the excretion rate of retinol-binding protein (RBP), N-acetyl-beta-D-glucosaminidase (beta-NAG) and glucose were significantly higher in IDDM subjects compared to control subjects (Mann-Whitney test, p = 0.02, < 0.001, < 0.001 and < 0.001, respectively), whilst the two groups had similar SLC and TmPO4 levels. There was no significant relationship between SLC and the other variables in IDDM subjects, even when comparing IDDM subjects with normal and high SLC. beta-NAG excretion rate was correlated to urinary glucose (rs 0.47, p = 0.001) and, weakly, to the other markers of glycaemic control (fasting blood glucose rs = 0.31, p = 0.03, fructosamine rs 0.28, p = 0.04, HbA1 rs 0.27, p = 0.04). RBP excretion rate was correlated to the excretion rate of beta-NAG (rs 0.38; p = 0.007) and albumin (rs 0.45; p = 0.002); the excretion rates of beta-NAG and albumin were significantly associated (rs 0.37, p = 0.009). Diabetes duration did not correlate to any of the aforementioned variables. In this study, beta-NAG and RBP overnight excretion rates were higher in normoalbuminuric IDDM subjects compared to control subjects but no relationship was present between SLC and tubular function in IDDM patients without complications. Excretion rates of different proteins appear to be interrelated and, in IDDM, beta-NAG excretion is associated with glycaemic control.
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PMID:Measures of tubular function in normoalbuminuric insulin-dependent diabetic patients and their relationship with sodium lithium countertransport activity. 885 60


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