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)

Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.
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PMID:Low molecular weight proteins in children with renal disease. 128 25

The urinary excretion of retinol-binding protein (RBP) was studied in 101 insulin-dependent diabetic patients allocated to three groups according to 24-h urinary albumin excretion rate (UAE) (median of three urine collections): group 1 (n = 45), normal UAE less than 30 mg/24 h; group 2 (n = 27), microalbuminuria (UAE 30-300 mg/24 h); and group 3 (n = 29), clinical diabetic nephropathy (UAE greater than 300 mg/24 h). We used 23 healthy subjects as controls. Fractional clearance of RBP (FC-RBP) and its 24-h urinary excretion rate (URBP) were higher in each diabetic group than in healthy subjects, the highest values being found in group 3. Groups 1 and 2 did not differ in URBP and FC-RBP. There was a correlation between FC-RBP and haemoglobin A1c in both the total diabetic cohort (P less than 0.001) and in diabetic patients in groups 1 and 2 with a glomerular filtration rate of more than 90 ml/min (P less than 0.05). No correlation was found between FC-RBP and UAE and/or duration of diabetes in any of the diabetic groups. We conclude that the increased urinary excretion of RBP, indicating proximal tubular dysfunction, is already present in normoalbuminuric insulin-dependent diabetic patients and correlates with metabolic control. Further deterioration in proximal tubular function was not observed in microalbuminuric patients, but is a late event in clinical diabetic nephropathy.
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PMID:Urinary excretion of retinol-binding protein in type 1 (insulin-dependent) diabetic patients with microalbuminuria and clinical diabetic nephropathy. 157 56

The measurement of small but abnormal amounts of albumin in urine is important in evaluating kidney disease in people with diabetes mellitus, hypertension, or possible adverse health effects from exposure to nephrotoxins. Routine laboratory methods for measuring albumin are not sensitive enough to measure the amounts that are significant in urine (less than 30 mg/L). In our laboratory we used three immunoassays for measuring urinary albumin: enzyme-linked immunosorbent assay (EIA), radioimmunoassay (RIA), and immunoturbidimetric assay (IT). We calculated the CVs of the three methods, investigated potential interfering substances at three times their normal concentrations, and stored urine under different conditions to find the best way to protect the sample until assay. The potential interferents we checked were transferrin, urea, beta 2-microglobulin, retinol-binding protein, creatinine, kappa and lambda light chains, IgG, hemoglobin, ketone, and glucose. The stability study involved two study temperatures (-20 and -70 degrees C) and four treatments (centrifuging or filtering, before or after storage). We found the following: the RIA had the lowest CV; the results from the interference study showed no interference from normal physiological concentrations of the substances investigated; storage at -70 degrees C regardless of the treatment should be adequate to prevent loss of albumin immunoreactivity.
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PMID:Considerations when measuring urinary albumin: precision, substances that may interfere, and conditions for sample storage. 176 88

The nature and origin of proteinuria in diabetes mellitus have been investigated by measuring the urinary excretion of seven specific proteins of low (beta 2-microglobin, retinol-binding protein) or high molecular weight (albumin, transferrin, hemopexin and IgG). Using the Alcian Blue binding test, we also measured negative charges on red blood cell (RBC) membrane which according to recent studies might mirror the glomerular polyanion charge. A group of 190 diabetics was examined, including 90 patients with type I diabetes, 23 type II diabetics treated with diet and/or hypoglycaemic agents and 77 longstanding type II diabetics requiring insulin therapy. With the exception of beta 2-microglobulin all proteins measured were excreted in the urine of diabetics in significantly higher amounts than in controls. The assay of transferrin proved the most sensitive (58% positive) followed by albumin (49%), IgG (34%), hemopexin (28%) and retinol-binding protein (26%). Practically the same ranking was obtained when only type I diabetics were considered. RBC membrane negative charges were diminished in diabetics and negatively correlated with the urinary excretion of albumin (r = -0.61, n = 190). RBC charges were also negatively correlated with other urinary proteins of high molecular mass (r between - 0.5 and - 0.2) but presented no relation with urinary beta 2-microglobulin or retinol-binding protein. The loss of RBC charges in diabetics most likely reflects the concomitant depletion of the glomerular polyanion responsible for the increased glomerular leakage of high molecular mass plasma proteins. The preferential increase in transferrin excretion together with the progressive rise in the urinary excretion of IgG lead us to postulate that the loss of glomerular polyanion in diabetes is accompanied, from the early stage, by a progressive decrease in the size-selectivity of the glomerular filter. The urinary excretion of retinol-binding protein was weakly correlated with albuminuria (r = 0.26, n = 186). Eight % of diabetics showed an elevation of urinary retinol-binding protein without evidence of microalbuminuria, which clearly demonstrates that a proximal tubular impairment can occur independently of the glomerular alterations in the course of diabetic nephropathy.
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PMID:Urinary proteins and red blood cell membrane negative charges in diabetes mellitus. 225 3

Urinary excretion of albumin and retinol-binding protein (a marker of tubular proteinuria that results from impaired proximal tubular reabsorption of low-molecular-weight proteins) was determined in 110 insulin-dependent diabetic (IDDM) subjects. A statistically significant correlation between the urinary excretion of both proteins, in particular the retinol-binding protein, and the height of arterial blood pressure (systolic and diastolic) was observed. Correlation was weak, i.e., factors other than incipient nephropathy could be of greater importance for the development of arterial hypertension in diabetes.
Diabetes Care 1990 Apr
PMID:Arterial blood pressure related to degree of albuminuria and low-molecular-weight proteinuria in IDDM. 231 4

In 109 patients with insulin-dependent diabetes mellitus (IDDM), we measured the urinary excretion of albumin, the low molecular weight proteins (LMWP) retinol-binding protein (RBP) and beta 2-microglobulin (beta 2m), and brush-border antigens (BBA) revealed by monoclonal antibodies. All such markers of kidney damage and/or dysfunction were higher in diabetic patients than in 44 controls. Increased urinary levels of BBA (p = 0.0001) were associated with higher values of albumin (p = 0.0002), RBP (p = 0.0005) and, to a lesser extent, of beta 2m (p = 0.1), different combinations of values above the reference limits being observed. Some 30 and 40% of patients with and without microalbuminuria, respectively, also exhibited signs of tubulopathy. Although under certain circumstances tubular defects may give rise to small increases in albuminuria, the most likely explanation for our findings is the coexistence of glomerular and tubular damage in some patients with IDDM. Neither the prognostic value nor the pathophysiological meaning of tubular damage and/or dysfunction can be assessed by the present study, owing to its cross-sectional design. Tubular markers thus deserve further studies to clarify whether in diabetic patients they indicate a more severe or diffuse kidney impairment.
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PMID:Urinary excretion of brush-border antigen and plasma proteins in early stages of diabetic nephropathy. 237 16

The urinary excretion of two low-molecular-weight proteins (beta 2-microglobulin and retinol-binding protein) was measured in 12 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with normal albumin excretion; reference ranges for the excretion of beta 2-microglobulin (beta 2M) and retinol-binding protein (RBP) were also obtained in 40 non-diabetic subjects. To ensure the stability of beta 2M in urine a urinary pH greater than or equal to 7 was achieved by giving oral sodium bicarbonate. beta 2M and RBP excretion was significantly higher in the diabetics than in the controls (p less than 0.01), but no higher in microalbuminuric than non-albuminuric diabetics. In the diabetics as a group a significant correlation was found between the excretion of beta 2M and RBP (r = 0.53, p less than 0.01), but more patients had an abnormal excretion of beta 2M than RBP (p less than 0.001). No significant correlation was found between the urinary excretion of either low-molecular-weight protein and duration of diabetes, insulin dose, HbA1, urinary glucose excretion or systemic blood pressure. Measured under appropriate alkaline conditions beta 2M appears to be more sensitive than RBP in detecting an abnormality of the renal proximal tubule which may be an early feature of diabetic renal involvement not characterized by microalbuminuria; microalbuminuria may have glomerular and tubular components.
Diabetes Res 1989 Sep
PMID:Low-molecular-weight proteinuria in insulin-dependent diabetes mellitus: a study of the urinary excretion of beta 2-microglobulin and retinol-binding protein in alkalinized patients with and without microalbuminuria. 269 3

A highly sensitive enzyme linked immunoadsorbent assay for determining retinol-binding protein in urine and serum is described. Commercially available reagents are used. The standard curve ranges from 1.2-24 micrograms/l, recovery of retinol-binding protein added to urine was 99-102% (n = 10) and dilution of urine was linear. The within-assay coefficient of variation ranged from 1.2-3.1% and the day-to-day coefficient of variation from 9.2-10.5% depending on concentration. The correlation with urinary retinol-binding protein determined by radioimmunoassay was good (n = 90, r = 0.95). In vitro experiments show that retinol-binding protein is stable in urine with pH 5.2.
Diabetes Res 1989 Feb
PMID:Micro-ELISA for the quantitation of human urinary and serum retinol-binding protein. 274 13

Serum concentrations of vitamins A and E and retinol-binding protein (RBP) were measured in 25 late adolescent and young adult patients with insulin-dependent diabetes mellitus. Their serum vitamin A levels were significantly lower than those of nondiabetic control subjects of comparable age. The serum concentrations of RBP were also significantly lower in the diabetic patients. The serum levels of vitamin A in the diabetic patients as well as in the control subjects showed a significant linear regression with serum concentrations of RBP. Unlike vitamin A, serum concentrations of vitamin E were not significantly different between the two groups of subjects. These findings suggest that the reduced serum vitamin A levels in the diabetic patients reflect reduced mobilization of vitamin A from the liver.
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PMID:Serum vitamin A and retinol-binding protein in patients with insulin-dependent diabetes mellitus. 275 19

Urinary excretion of the retinol-binding protein (RBP) was studied in 36 insulin-dependent diabetics with serum creatinine concentrations within the normal range and no microalbuminuria. The excretion was significantly (p less than 0.05) higher in the diabetics as compared to a group of apparently healthy persons. The diabetes control indices HbA1 and serum fructosamine showed no correlation to the rate of urinary RBP excretion. The present data support the idea that tubular dysfunction may be an early symptom of diabetic nephropathy.
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PMID:Increased urinary excretion of the retinol-binding protein in insulin-dependent diabetes mellitus in the absence of microalbuminuria. 343 68


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