Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive hypertensive insulin-dependent diabetes patients with nephropathy (mean age, 33 years) who had not been treated previously were all treated with captopril in combination with frusemide or bendrofluazide. The four patients who were refractory to this regimen also received nifedipine. Treatment was continued for a median of 8.9 years (range, 6.3 to 9.8, years). Renal function was assessed every 6 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and albuminuria by radioimmunoassay. Baseline values (+/- SE) were mean arterial blood pressure 146/93 +/- 3/1 mm Hg, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P < 0.01) and albuminuria (392 +/- 1.4 microns/min; P < 0.01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P < 0.01), hemoglobin A1c (r = 0.69, P < 0.01), and serum total cholesterol concentration (r = 0.51, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin-converting enzyme inhibition in diabetic nephropathy: ten years' experience. 761 Dec 76

Abnormalities in extracellular matrix degradation may play a pathogenetic role in diabetic nephropathy. Cultured renal mesangial cells are known to synthesize increased amounts of matrix proteins when incubated in high glucose media (e.g., 30 mmol/l). However, the effect of glucose loading on degradative enzymes is unknown. Primary cultures of rat mesangial cells were grown until confluent in the presence of fetal calf serum (FCS) and insulin (0.67 U/ml). Cells were then cultured for 7 days in plastic wells in either 10 or 30 mmol/l glucose media containing neither FCS nor insulin. Collagenase activity in media were determined by zymography and quantitative spectrofluorometry. Cathepsin B and D activities in cell extracts were measured by spectrofluorometry (using the fluorescent substrate Z-Arg-Arg-7-amido-4-methylcoumarin) and 125I-labeled hemoglobin digestion, respectively. Gelatin-degrading activity of live mesangial cells was also determined. mRNA levels for collagenase IV, cathepsin B, and cathepsin D were determined by Northern analysis. A major band of collagenase activity with a molecular size of 72 kDa was observed in all mesangial cell media. Exposure of cells to high glucose media resulted in significant reductions in collagenase and cathepsin B activities as well as impairment in gelatin-degrading activity. Collagenase IV and cathepsin B and D mRNA levels were also decreased by glucose loading. To exclude the possibility that glucose loading was injurious to cells, 3H-leucine uptake (as a measure of protein synthesis) and membrane alkaline phosphatase activity (as a biochemical marker of viability) were not affected by the high glucose condition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased degradative enzymes in mesangial cells cultured in high glucose media. 762 99

Increased erythrocyte sodium-lithium countertransport activity has been implicated in the pathogenesis of diabetic nephropathy. However, its relationship to other cation membrane transport systems in incipient nephropathy is not yet clear. The present study was thus performed to: (1) explore associations between sodium-lithium countertransport and changes in the activity of other cation transport pathways and (2) to compare the sodium transport activities with clinical characteristics of insulin-dependent diabetic patients with and without evidence of incipient diabetic nephropathy. We measured erythrocyte sodium-lithium countertransport, passive sodium/potassium flux (at 1 degree C), adenine nucleotide content in intact erythrocytes and sodium/potassium-, magnesium- and calcium-dependent ATPase activity in erythrocyte membrane preparations from 34 insulin-dependent diabetic patients without microalbuminuria, 8 diabetic patients with microalbuminuria, and 8 age-matched healthy control subjects. Sodium-lithium countertransport was elevated in diabetic patients with normo- and microalbuminuria compared with control subjects [268 +/- 99 and 299(277-465), respectively, vs. 166 +/- 65 mumol/(1 cells x h)] and was positively correlated (r = 0.36, P < 0.05) with the albumin excretion rate. However, the activity of erythrocyte membrane ATPases was significantly decreased compared with control subjects. The ATP and ADP content was found to be significantly higher (P < 0.001) in erythrocytes from diabetic patients compared with control subjects (1,196 +/- 276 vs. 833 +/- 253 mumol/l cells and 353 +/- 97 vs. 255 +/- 64 mumol/l cells, respectively). The extent of erythrocyte potassium leakage correlated with hemoglobin A1c (r = 0.39, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythrocyte sodium-lithium countertransport, adenosine triphosphatase activity and sodium-potassium fluxes in insulin-dependent diabetes. 766 4

Plasma glucose, glycated hemoglobin lc (HbAlc), urinary albumin excretion rate (AER) and urinary N-acetyl-glucosaminidase (NAG): creatinine ratio were studied in 100 normotensive diabetic patients with no evidence of overt renal disease and in 45 controls, to find out whether the glycaemic control and incipient nephropathy may influence the urinary excretion of NAG. Twenty-three of the diabetics had microalbuminuria (group II). Group I comprised the 77 diabetics without microalbuminuria. The groups I and II of diabetics were divided into two according to plasma glucose were greater o smaller to 140 mg/dl. The group I of diabetics had greater NAG: creatinine ratio than controls, too (0.41 +/- 0.24 and 0.16 +/- 0.08 mu/mmol creatinine, p < 0.0005); in this group urinary NAG was found to positively correlate with plasma glucose and creatinine (p < 0.0005, r = 0.45). Multiple regression analysis was performed in the whole of diabetics and significant association were identified between urinary NAG excretion and plasma glucose, AER and plasma creatinine (p < 0.0005, r = 0.42). The diabetics with plasma glucose lower to 140 mg/dl had more important correlation NAG: creatinine ratio-AER (p < 0.0001, r = 0.70). It is concluded that measurement of urinary NAG may be of value in the detection of diabetic nephropathy at a potentially reversible stage if the plasma glucose is take into account.
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PMID:[Influence of glycemic blood glucose control and incipient diabetic nephropathy on the urinary excretion of N-acetyl-glucosaminidase (NAG) in diabetes mellitus]. 766 72

Monoclonal antibodies were raised against urine proteins from diabetic patients. An antibody, YO-2, stained three protein bands with apparent molecular weights of 66, 49, and 36 kDa. These bands were not reactive with an anti-human albumin antibody. The urine levels of YO-2-reactive antigen in the normal control were 0.97 +/- 0.37 U/g-Cr (units per gram of urine creatinine) (mean +/- SD). Those of the normo-, micro-, and macroalbuminuric diabetic patients, respectively, were 1.38 +/- 1.36, 2.87 +/- 2.07, and 3.92 +/- 3.33 U/g-Cr. They were significantly higher in the micro- and macroalbuminuric patients. The urine levels of YO-2-reactive antigen had no significant correlation with the urine albumin levels and hemoglobin A1c. We concluded that; a) monoclonal antibody YO-2 recognized a non-albumin urine antigen increasingly excreted in diabetic patients with nephropathy, b) recent glycemic control of diabetes would not significantly affect the urinary excretion rate of YO-2-reactive antigen, and c) the excretion rate and probably the mechanism of YO-2-reactive protein differed from those of albumin. The urine levels of YO-2-reactive antigen could be a clinical marker of diabetic nephropathy.
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PMID:Increased urinary excretion of non-albumin antigen detected with YO-2, a novel monoclonal antibody, in diabetic patients. 767 46

Relationship of the lipoprotein(a) [Lp(a)] concentration as a risk factor independent of other factors with the severity of diabetic retinopathy were evaluated by multiple regression analysis. The subjects were 158 patients with non-insulin-dependent diabetes mellitus (NIDDM). Multiple regression analysis was carried with the severity of diabetic retinopathy as the dependent variable and 13 independent variables, namely the Lp(a) concentration, sex, age, body mass index, duration of diabetes, ischemic heart disease, fasting plasma glucose, glycosylated hemoglobin A1c, total cholesterol, triglyceride, high-density lipoprotein cholesterol, anti-diabetic treatments, and diabetic nephropathy. The analysis was performed separately in all subjects, males only, and females only. The standard partial regression coefficient of Lp(a) was significant (0.293, p < 0.01), and the multiple correlation coefficient was 0.611 in the males. However, the standard partial correlation coefficient of Lp(a) was not significant in all patients and in females only. The rank of contribution of Lp(a) to retinopathy was the third in males, following triglyceride and nephropathy and followed by anti-diabetic treatments. These results suggest that Lp(a) might be an independent risk factor for diabetic retinopathy in male patients with NIDDM.
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PMID:Lipoprotein(a) as an independent risk factor for diabetic retinopathy in male patients in non-insulin-dependent diabetes mellitus. 781 85

Patients with diabetes mellitus are more frequently hypertensive than age-matched non-diabetic subjects. They are confronted with a markedly increased risk of coronary vascular disease, of progressive nephropathy and renal end-stage diseases. The most common type of hypertension in type I and type II diabetics is essential hypertension, probably as a consequence of insulin resistance and hyperinsulinemia. Hyperglycemia and hypertension are both significantly involved in the progression of diabetic nephropathy. Hence, the modern therapeutic concept consists of optimal blood glucose control and strict blood pressure control. Progression of the nephropathy may be halted in most of the cases by adhering to set limits in mean arterial blood pressure, glycated hemoglobin and urinary albumin excretion rate. Furthermore, a significant decrease in cardiovascular mortality may be achieved. In case the blood pressure targets cannot be met by non-drug therapies and life-style modifications, antihypertensive drug therapy has to be initiated. The selection of antihypertensives should be based on the concomitant diabetes mellitus with its additional cardiovascular risk factors hyperlipidemia and hyperinsulinemia. In general, preference should be given to so-called metabolic neutral substances such as ACE inhibitors or calcium antagonists or to alpha-blockers which may have positive metabolic effects. Meanwhile, data from several prospective studies claim that ACE inhibitors and calcium antagonists exert nephroprotective effects beyond their beneficial blood pressure lowering effects, thereby preventing the progression of diabetic nephropathy. However, these drugs should not be uncritically used and we should be aware of their potential adverse effects. The differential therapy of hypertension in diabetes mellitus requires mature consideration before initiation of therapy, an individualized concept of therapy, and careful monitoring during treatment.
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PMID:[Hypertension, microalbuminuria and insulin resistance in diabetes mellitus]. 784 97

The clinical diagnosis of diabetes is often prompted by symptoms such as increased thirst and urine volume, and weight loss. High levels of glucosuria are usually present. A single blood glucose estimation of diagnostic value indicated > or = 200 mg/dl at random, or > or = 140 mg/dl at fasting in specimens of venous plasma. Only if blood glucose values lie in the uncertain range (i.e., between the level that establish or exclude diabetes) need an oral glucose tolerance test (OGTT) be considered in order to establish the diagnosis status. Diagnostic interpretation of the 75 g OGTT responses is performed by the criteria of the expert committee of the Japan Diabetic Society. Glycated hemoglobin (HbA1c, HbA1) is widely used as a cumulative estimate of the mean blood glucose concentration over the preceding one approximately two months. Reference ranges of HbA1c are 4 approximately 6%. Labile glycohemoglobin often influences the estimate. Fructosamine and glycated albumin are also used as means of evaluating the degree of control. These data reveal the mean blood glucose concentration over the preceding 2 weeks. 1.5-Anhydroglucitol in blood is measured as a means of diagnosis and control evaluation of diabetes. Microalbuminuria is widely measured for early detection of diabetic nephropathy. Recently other microproteinuria such as urinary transferrin and IgG are assayed for the same purpose. There are highly significant correlations between microalbuminuria and urinary transferrin or IgG.
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PMID:[Clinical laboratory tests in diabetes mellitus]. 793 14

The study included 108 IDDM patients (59 males, 49 females, aged 15-59 years) from the Bucharest Diabetic Centre which participated in the EURODIAB multicentric study. They were divided into three groups according to the duration of diabetes (less than 7 years; 8 to 14 years; more than 15 years) and we have made a comparison between the importance of some risk factors, as elevated blood pressures, age, elevated levels of the total plasma cholesterol, and glycosylated hemoglobin (HbA1C) on the progression of the microalbuminuria in these groups. Excluding the patients in the renal failure stage of the diabetic nephropathy or with other chronic diseases, our results confirm the data in the literature referring to the important role of the elevated diastolic blood pressure and elevated levels of the total plasma cholesterol in the rapid progression of the renal injury, especially after more than 8 years of IDDM evolution. We also found, between the long-term diabetics (over 15 years of evolution) a large proportion which appears to be genetically protected against the diabetic nephropathy. This point confirms some data from the literature (the Steno hypothesis). The HbA1C levels appears to lower with the duration of the diabetes and they are not correlated with the degree of the renal injury. These findings appear to be in contradiction with the data from the literature.
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PMID:Risk factors and risk determinants for the evolution of the diabetic nephropathy in IDDM: a case control study of 108 IDDM patients in the Bucharest Center of Diabetes. 814 76

Antihypertensive therapy reduces the rate at which glomerular filtration rate (GFR) declines (delta GFR) in diabetic nephropathy; however, the optimal blood pressure is unknown. The quantitative relationship between treated blood pressure and delta GFR was analyzed retrospectively in 59 patients with established diabetic nephropathy and treated hypertension using weighted univariate and weighted multivariate regression. The GFR was calculated using the Cockcroft and Gault formula. More rapid GFR loss correlated most strongly with higher diastolic blood pressures (r = 0.70; P < 0.0001); for each millimeter of mercury of diastolic blood pressure, the GFR decreased by 0.69 mL/min/yr. This relationship remained present if those individuals with diastolic pressures greater than 90 mm Hg were eliminated from the study (r = 0.50; P < 0.001). The correlation for systolic blood pressure was weaker (r = 0.30; P < 0.05) and explained completely by covariance between systolic and diastolic blood pressures. The correlation for mean blood pressure (r = 0.59; P < 0.0001) fell between the correlations for diastolic and systolic blood pressures. Proteinuria, serum albumin concentration, and serum cholesterol concentration also correlated with delta GFR. In multivariate analysis, neither these indices of disease severity nor the initial GFR explained the correlation between delta GFR and diastolic blood pressure. Age, sex, race, type of diabetes, and percentage of glycosylated hemoglobin did not correlate with delta GFR.
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PMID:The quantitative relationship between treated blood pressure and progression of diabetic renal disease. 825 25


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