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Query: UMLS:C0011849 (diabetes)
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The predictive value of tubular proteinuria and/or enzyme excretion for the development of microalbuminuria in patients with diabetes mellitus was investigated over a period of 7.5 years in 64 children and adolescents without microalbuminuria at baseline. An abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) preceded the increase of albumin excretion in all 8 patients (12.5%) developing microalbuminuria during this period (positive/negative predictive value 0.2 and 1.0, respectively). Also both, the actual as well as the long-term glycemic control (HbAlc) up to the onset of abnormal NAG excretion were predictive for the development of microalbuminuria. Fifty percent of those patients with both an elevated NAG excretion and an HbAlc > or = 9% developed micro-albuminuria within the next 5 years. Therefore, periodic monitoring of urinary NAG excretion should be incorporated into the follow-up of patients with type 1 diabetes mellitus.
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PMID:Predictive value of tubular markers for the development of microalbuminuria in adolescents with diabetes. 967 93

Rosiglitazone (BRL 49653), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist and potent insulin action-enhancing agent, was given in the diet (50 micromol/kg of diet) to male Zucker rats ages 6-7 weeks for 9 months (prevention group). In this treatment mode, rosiglitazone prolonged the time to onset of proteinuria from 3 to 6 months and markedly reduced the rate of its subsequent progression. Progression was also retarded when treatment was commenced (intervention group) after proteinuria had become established (4 months; ages 24-25 weeks). In either treatment mode, rosiglitazone normalized urinary N-acetyl-beta-D-glucosaminidase activity, a marker for renal proximal tubular damage, and ameliorated the rise in systolic blood pressure that occurred coincidentally with the development of proteinuria in Zucker fatty control rats. The renal protective action of rosiglitazone was verified morphologically. Thus in the prevention group there was an absence of the various indexes of chronic nephropathy that were prominent in the Zucker fatty control group, namely, glomerulosclerosis, dilated tubules containing proteinaceous casts, a loss of functional microvilli on the tubular epithelium, and varying degrees of chronic interstitial nephritis. An intermediate pathology was observed in the intervention group. Also, pancreatic islet hyperplasia, ultrastructural evidence of beta-cell work hypertrophy, and derangement of alpha-cell distribution within the islet were prominent features of Zucker fatty control rats, but these adaptive changes were ameliorated (intervention group) or prevented (prevention group) by rosiglitazone treatment. These data demonstrate that treatment of Zucker fatty rats with rosiglitazone produced substantial protection over a prolonged period against the development and progression of renal injury and the adaptive changes to pancreatic islet morphology caused by sustained hyperinsulinemia.
Diabetes 1998 Aug
PMID:Peroxisome proliferator-activated receptor-gamma agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats. 970 35

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a new genetic model of non-insulin-dependent diabetes mellitus (NIDDM). We investigated whether treatment with an angiotensin II (ANGII) subtype-1 receptor antagonist delays the onset of NIDDM and attenuates diabetic nephropathy in the OLETF rat. OLETF rats fed a regular chow were treated with ANGII subtype-1 receptor antagonists (E4177 or TA606) for 22 weeks. Hemodynamic changes, glucose metabolism, and the effects on diabetic nephropathy were examined. Systolic blood pressure increased in OLETF rats in an age-dependent manner. OLETF rats exhibited increases in plasma concentrations of glucose and insulin and developed glucosuria at the age of 28 weeks. The changes in glucose metabolism were associated with proteinuria and an increase in urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG). Morphologic investigation revealed nodular lesions in glomeruli in the OLETF rats. The ANGII receptor antagonist treatment abolished the blood pressure elevation. However, the treatment did not affect plasma glucose and insulin levels and did not significantly reduce glucosuria. Nodular lesions in glomeruli were not improved by the treatment. However, the receptor antagonists significantly reduced proteinuria and urinary NAG excretion. Multivariate analyses revealed that proteinuria was determined by systolic blood pressure, lipid metabolism, and glucose levels in plasma. ANGII subtype-1 antagonism does not improve glucose metabolism in the OLETF rat model of NIDDM, which has abnormalities in the glucose-uptake system. Blood pressure elevation and part of the proteinuria associated with NIDDM depends on the renin-angiotensin system rather than glucose metabolisms per se.
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PMID:Angiotensin II subtype-1 receptor antagonists improve hemodynamic and renal changes without affecting glucose metabolisms in genetic rat model of non-insulin-dependent diabetes mellitus. 1007 80

We studied the relationship between the urinary microtransferrin (TRF) and early glomerular damage in diabetes mellitus. 61 patients with non-insulin-dependent diabetes mellitus and 40 healthy subjects were measured for urinary TRF with rate immunonephelometry assay. The Urinary TRF concentrations were found to be greatly elevated in patients with diabetes compared with those in the health subjects (P < 0.001). The increase of TRF was closely related to age and duration of diabetes mellitus, blood glucose, hypertension, retinopathy, and it was initial parameter to predict diabetic nephropathy. There was a significant correlation among urinary TRF concentration, microalbumin, and N-acetyl-beta-D-glucosaminidase. The urinary excretion of TRF was more elevated than that of microalbumin. It is suggested that excretion of TRF in urine is a more sensitive index of the glomerular dysfunction in diabetes mellitus.
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PMID:[Clinical significance of microtransferrinuria in diabetic patients]. 1037 8

The erythrocyte membrane in 71 patients with type 2 diabetes mellitus was assessed for glycohydrolase activity: N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha- and beta-D-galactosidase, alpha- and beta-D-glucosidase, alpha-D-mannosidase, and alpha-L-fucosidase. Only beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase showed markedly elevated levels with respect to the controls regardless of the presence of complications. Among the examined patients, those with good metabolic control (not yet submitted to any therapy) showed the same enzyme levels as the reference subjects, while the levels in patients with unsatisfactory metabolic control (treated with oral hypoglycemic and/or insulin) significantly differed from the control levels. For alpha-D-glucosidase and beta-glucosidase, a correlation with glycemia and the parameters of metabolic control was also evidenced. Alterations of beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase were also ascertained in the plasma of the same diabetic patients according to the literature; each enzyme correlated with the other, either in plasma or in the erythrocyte membrane. This study shows a correlation between plasma and erythrocyte membrane levels for these three enzymes. The strict parallelism of the glycohydrolases in the two different compartments provides a profile of these enzymes in the pathology of diabetes.
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PMID:Alterations in the activity of several glycohydrolases in red blood cell membrane from type 2 diabetes mellitus patients. 1042 Dec 18

The measurement of urinary enzymes in patients with diabetes mellitus has become a useful additional test for the early detection of nephropathy. Controversy persists concerning methods of measurement since during early stages of insulin-dependent diabetes mellitus children develop the so-called hyperfiltration syndrome. This study was performed to determine whether elevated levels of excreted creatinine influence the determination of the enzyme N-acetyl-beta-D-glucosaminidase (NAG). Reference values for NAG in single-spot urines (units NAG/mmol creatinine) and in 24-h collections (units NAG/l urine) were established in two different groups of 105 and 111 healthy children. NAG was then measured in single-spot urines (as NAG/mmol creatinine) and in collection urines of 30 diabetic children within the same 24-h period and compared with the reference population. These results were compared with hemoglobin (Hb)A1(a-c) and fructosamine values as well as creatinine clearance of the diabetic patients. There was a direct correlation between the NAG levels in single-spot and 24-h urine collections of diabetic patients. However, the NAG/creatinine ratio in the single-spot urines did not correlate with the HbA1(a-c) or fructosamine level. When 24 h collections (expressed as NAG/l) were used, the results correlated well with HbA1(a-c) and fructosamine. There was an inverse correlation between the creatinine clearance and the NAG/creatinine ratio, i.e., a high creatinine clearance correlated with a low NAG/creatinine ratio. This was not the case for 24 h collections (expressed as units/l). Hence, in children with insulin-dependent diabetes mellitus 24-h urine collections should be used for urinanalysis. Parameters should not be related to creatinine, since the ratio of urinary protein and creatinine is unreliable because of the high urinary creatinine during the hyperfiltration state.
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PMID:Influence of hyperfiltration on the measurement of urinary N-acetyl-beta-D-glucosaminidase. 1045 82

An early manifestation of diabetic nephropathy, increased excretion of albumin, is now generally believed to be sufficiently specific, particularly in subjects with diabetes mellitus, to predict the subsequent development of clinically overt diabetic nephropathy. However, certain other proteins besides albumin may also be excreted in abnormal amounts during this early phase of diabetic nephropathy. We evaluated the diagnostic utility of urinary immunoglobulin G (IgG) in patients with diabetic nephropathy by comparing the findings with the clinical stage and renal biopsy specimen. Using 24-hour urine samples, IgG was measured by an enzyme-linked immunosorbent assay. In addition, urine samples were assayed for albumin, transferrin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Serum IgG concentration and HbA1c were also evaluated. A total of 197 patients with non-insulin-dependent diabetes mellitus were enrolled in this study. Subjects were grouped according to the rate of urinary albumin excretion (clinical stage). Fifty of these cases were also divided into four groups according to the severity of diffuse glomerular lesions using Gellman's criteria. The urinary excretion of IgG was significantly increased in diabetic patients as compared with the healthy controls. Among diabetic patients, IgG level showed a significant increase with respect to the clinical stage of nephropathy and the progress of glomerular diffuse lesions. In the stage of normoalbuminuria, the urinary excretion of IgG showed a significant increase in parallel with the progress of glomerular diffuse lesions, whereas there was no relationship between the urinary excretion of albumin and the progress of glomerular diffuse lesions. While the excretion of IgG correlated with that of albumin and transferrin, there was no correlation between the excretion of IgG and the other laboratory indices evaluated. These findings indicate that measurement of urinary IgG may be more useful than albuminuria in detecting the early stage of diabetic nephropathy.
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PMID:[Diagnostic significance of urinary immunoglobulin G in diabetic nephropathy]. 1065 27

N-acetyl-beta-D-glucosaminidase (NAG) is released from lysosomes, but the clinical significance of its serum activity in the pathogenesis of coronary artery disease has not been well understood. We measured serum NAG activity by a colorimetric method in consecutive 168 patients suspected of having coronary artery disease who underwent diagnostic coronary angiography. In addition, we evaluated the relationship between the activity and severity of coronary artery disease, as well as various coronary risk factors. Serum NAG activity was higher in the multi-vessel disease group than in the no stenotic lesion group (9.2+/-2.3 vs. 7.8+/-1.8 U/l, P<0.01) and in the single-vessel disease group (vs. 8.2+/-2.2 U/l, P<0.05). In all patients, Gensini score was closely correlated with the serum NAG activity (r = 0.39, P<0.001). Multiple regression analysis showed that serum NAG activity was correlated with plasma insulin level (r = 0.49, P<0.01), but not correlated with other coronary risk factors. In 126 patients without apparent diabetes mellitus, serum NAG was also correlated with plasma insulin level (r = 0.37, P<0.01) and additionally with insulin resistanc determined by homeostasis model assessment (r = 0.47, P<0.01). Our results suggested that serum NAG activity correlates with the severity of coronary artery disease in relation to plasma insulin level and insulin resistance, and thus can be an indicator of coronary artery disease based upon abnormalities of glucose metabolism.
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PMID:Serum N-acetyl-beta-D-gulucosaminidase activity increases in association with insulin resistance in patients with coronary artery disease. 1070 22

The study investigated the prevalence of incipient renal dysfunction in two cohorts with identical duration of type I diabetes but with childhood or adult onset of the disease. The pattern of glomerular (albumin, alb) and tubular (alpha(1)-microglobulin, alpha(1)-m, and N-acetyl-beta-D-glucosaminidase, NAG) urinary protein excretion was studied in 97 patients with diabetes onset before the age of 16 years and in 53 patients with manifestation of the disease after this age. Diabetes duration was comparable in both groups [9.0 years (1.5-40.0) versus 9.0 (1.0-34.0), p 30 microg/g creatinine), patients with diabetes onset in childhood showed significantly higher excretion of NAG compared to those with diabetes onset after the age of 16. The excretion of both tubular markers (alpha(1)-m and NAG) correlated significantly with HbA(1c)-values in both groups. In multiple regression analysis, tubular proteinuria (alpha(1)-m) and diabetes duration correlated significantly to microabuminuria (multiple R = 0.60, p < 0.001). These data suggest that there is no difference concerning the prevalence of incipient diabetic glomerulopathy between patients with an early or a late onset of diabetes. However, a more frequent impairment of tubular function was found in young patients with diabetes onset in childhood, which might be due to a non-optimal glycemic control in this population.
J Diabetes Complications
PMID:The prevalence of incipient tubular dysfunction, but not of glomerular dysfunction, is increased in patients with diabetes onset in childhood. 1076 10

The effect of hyperglycemia and insulin deficiency on the plasma level of lysosomal glycohydrolases, namely N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase, and alpha-D-glucosidase, was investigated. Two patient groups were assessed: (1) 28 children with type 1 diabetes at onset (fasting blood glucose, 444+/-154 mg/100 mL; hemoglobin A1c, 11.9%+/-2.4%; symptom duration, 15.9+/-8 days; and absence of complications), (2) 14 adult subjects undergoing an intravenous glucose tolerance test (IVGTT), consisting of 8 non-obese subjects (body mass index, 26+/-0.04 kg/m2; fasting blood glucose, 82+/-13 mg/100 mL; blood insulin, 6+/-0.04 mU/L) and 6 obese subjects (fasting blood glucose, 97+/-3.5 mg/100 mL; blood insulin, 27+/-6 mU/L, with normal oral glucose tolerance test). Enzyme activity was determined with the fluorimetric method. The mean level of all evaluated enzymes was significantly increased in patients with type 1 diabetes at diagnosis compared with normal controls. Increased enzyme levels were also detected in the group of adults undergoing an IVGTT in whom hyperglycemia was accompanied by insulin resistance (ie, obese subjects). Glycohydrolase abnormalities appear to be related to insulin deficiency rather than hyperglycemia. Lysosomal apparatus abnormalities seem to be an inherent feature of diabetes that is present at disease onset. The possible role of insulin in the regulation of plasma glycohydrolase levels is discussed.
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PMID:Plasma glycohydrolase levels in patients with type 1 diabetes at onset and in subjects undergoing an intravenous glucose tolerance test. 1107 28


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