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)

In this prospective study of 11.9 years duration (range 9 to 14), we examined the progression of albuminuria prior to and after the onset of microalbuminuria [albumin excretion rate (AER): 20 to 200 micrograms/minute]. Glycated hemoglobin (HbA1), AER and blood pressure were measured every six months. Twenty-two (13 type I, 9 type II) patients were identified in whom AER increased progressively (progressors). These patients were compared with 22 others matched for age, duration and type of diabetes in whom AER did not change significantly during the study period (non-progressors). In the progressors, the rate of increase in AER correlated with mean HbA1 for the study period in patients with type I (r = 0.68, P < 0.01) and type II diabetes (r = 0.71, P < 0.05). Furthermore, AER began increasing well before the conventional 20 micrograms/minute threshold of microalbuminuria had been reached and within the first five years of diagnosis of type I diabetes. We conclude that in predisposed diabetic patients, long-term glycemic control is correlated with the rate of development of early renal abnormalities. Repeated measurements of AER from the time of diagnosis may be useful in the early detection of patients who will develop microalbuminuria and ultimately overt diabetic nephropathy.
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PMID:Long-term glycemic control and the rate of progression of early diabetic kidney disease. 825 61

In a prospective follow-up of 30 patients with type 1 diabetes and nephropathy, serum cholesterol, triglycerides, apolipoprotein Al and B, and lipoprotein(a) were determined to study their relationship to the rate of decline in glomerular filtration rate. The patients had proteinuria and advanced nephropathy with a mean +/- SD glomerular filtration rate of 39 mL/min/1.73 m2. The decline in glomerular filtration rate was determined during 2.5 +/- 0.5 years. High serum cholesterol, triglycerides, and apolipoprotein B were correlated to a more rapid deterioration in kidney function. The rate of decline in glomerular filtration rate was 1.0 +/- 2.5 mL/min/yr in the 10 patients with the lowest cholesterol level, compared with 4.5 +/- 3.2 mL/min/yr in the patients with the highest serum cholesterol (P = 0.015). The combined effect of the measured lipids, blood pressure, type of antihypertensive treatment, protein intake, proteinuria, and hemoglobin A1C on the rate of decline in glomerular filtration rate was assessed by multiple regression analysis. The measured factors together had a high explanatory power for the rate of decline in glomerular filtration rate. In this model, 73% of the variation in decline in glomerular filtration rate was explained by the measured variables (multiple r2 = 0.73). Low cholesterol and treatment with an angiotensin-converting enzyme inhibitor were the strongest predictors of a favorable renal prognosis. This suggests that hypercholesterolemia is an important risk factor for diabetic nephropathy.
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PMID:Cholesterol: a renal risk factor in diabetic nephropathy? 832 83

We attempted to reevaluate the clinical significance of two parameters, 1,5-anhydroglucitol (AG) and type IV collagen, which are widely available in the fields of clinical activity. 1) 1,5 AG 1,5 AG was measured as a marker of glycemic control for diabetic patients by means of a column-enzymatic test (Nippon Kayaku Co., Ltd). Serum 1, 5 AG levels in diabetic patients (3.0 +/- 5.8 micrograms/ml, mean +/- SD) were significantly lower than in normal subjects (22.4 +/- 6.9 micrograms/ml). 75 g OGTT was performed on 428 subjects with urinary glucose detected on previous medical examination. According to the selectivity index (sensitivity value x specificity value) and the receiver operating characteristic curve (ROC) for diabetes, glycosylated hemoglobin (HbA1c) was slightly superior to 1,5 AG and fructosamine for diabetes screening. Furthermore, unexpectedly high levels of 1, 5 AG were obtained from the plasma of diabetic patients with this kit, when the patients were given a drip infusion containing maltose. We found that the maltose contained in the assay system interfered with measurement of 1, 5 AG. Nevertheless, 1, 5 AG measurements are thought to be useful in the diagnosis and screening of diabetes mellitus because of its wideranging fluctuations under relatively good glycemic control, as suggested by Yamanouchi, et al. 2) type IV collagen The type IV collagen peptide is known as a useful marker of progressive liver diseases and early stages of diabetic nephropathy. Type IV collagen was measured by one step sandwich enzyme immunoassay (EIA) using monoclonal antibodies (Panaassay IV CL; Fuji Chem. Ind., Ltd).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical markers in endocrine-metabolic diseases]. 835 14

Color Doppler imaging was used to investigate the changes in Pourcelot index (RI), which is an index for vascular resistance calculated from the blood flow velocity of the ophthalmic artery, related to the complications of diabetes mellitus (diabetic retinopathy, diabetic nephropathy) and systemic background (duration of diabetes mellitus, value of hemoglobin A1C (HbA1c)) in 46 diabetic patients and in 20 normal subjects. RI was significantly higher in diabetic patients than in normal subjects (p < 0.05). RI increased in patients without retinopathy (p < 0.05), in patients with background retinopathy (p < 0.05), and in patients with preproliferative or proliferative retinopathy (p < 0.05), but it did not change in patients after panretinal photocoagulation, compared with the normal subjects. In diabetic patients, RI was higher (p < 0.05) in patients with nephropathy than in those without nephropathy. The time from onset of diabetes mellitus and the value of HbA1c had no correlation with RI. Our results indicate that choroidal circulation was changed in diabetic patients compared with normal subjects and that the changes were related to diabetic nephropathy.
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PMID:[Analysis of blood flow velocity in the ophthalmic artery by color Doppler imaging. 2. Studies on diabetic eyes]. 836 85

The effect of dilazep, an adenosine potentiator and platelet aggregation inhibitor, on experimental diabetic nephropathy was investigated in spontaneous diabetic Chinese hamster. Prediabetic animals, 8 weeks of age, were divided into two groups. In one group, 5 mg/kg dilazep was injected i.p. once a day. In the other group, saline of the same amount was injected. Age- and sex-matched animals from a nondiabetic subline were used as controls. No difference was observed in body weight, mean blood pressure, fasting plasma glucose and glycated hemoglobin level between diabetic animals with and without dilazep administration throughout the entire period of experiment. Urinary protein excretions in untreated diabetic animals increased significantly compared to those of nondiabetic controls at 8 weeks (17.5 +/- 3.5 vs 2.0 +/- 0.1 mg/day), and at 24 weeks (25.3 +/- 5.1 vs 2.7 +/- 0.1 mg/day) of experiment. In diabetic animals with dilazep treatment, urinary protein excretions (4.1 +/- 0.7 at 8 weeks and 13.1 +/- 2.9 mg/day at 24 weeks of experiment) were significantly suppressed compared to those in untreated diabetic animals. Significant thickening of glomerular basement membrane (GBM) was observed in diabetic animals both with and without dilazep administration at 24 weeks of experiment compared to that in nondiabetic controls. The number of anionic sites in GBM, stained by polyethyleneimine, was reduced in untreated diabetic animals, but was not different in dilazep treated animals compared to that in nondiabetic controls. It was concluded that dilazep administration suppressed urinary protein excretion in diabetic Chinese hamster possibly through the preservation of charge barrier of the glomerulus.
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PMID:The effect of dilazep on urinary protein excretion in spontaneous diabetic Chinese hamster. 841 70

Hypertension is significantly involved in the progression of diabetic nephropathy and in the development of end stage renal disease in both type I and type II diabetes mellitus. We have investigated whether long-term monotherapy with a calcium antagonist, nitrendipine, prevents the development of overt diabetic nephropathy in type I and type II diabetic patients with mild to moderate hypertension and persistent microalbuminuria (ie, incipient nephropathy). After a 4-week run-in and washout period, respectively, 25 patients met the inclusion criteria. Twenty-two patients (six with type I and 16 with type II diabetes) completed the 12-month study. Twelve months of treatment with nitrendipine resulted in a significant reduction in systolic blood pressure in patients with type I (157.5 +/- 8.1 mm Hg v 135.8 +/- 4.2 mm Hg, P < 0.05) and type II (163.1 +/- 4.3 mm Hg v 135.9 +/- 3.6 mm Hg, P < 0.001) diabetes. A significant reduction also was seen in diastolic blood pressure (91.7 +/- 1.7 mm Hg v 79.2 +/- 3.5 mm Hg in type I diabetic patients, P < 0.01; 94.7 +/- 1.4 mm Hg v 78.1 +/- 1.5 mm Hg in type II diabetic patients, P < 0.001). A significant reduction in albuminuria was associated with the blood pressure reduction in both type I (57.8 +/- 11.9 mg/24 hr v 24.9 +/- 5.9 mg/24 hr, -57%) and type II (134.6 +/- 20.7 mg/24 hr v 70.3 +/- 16.8 mg/24 hr, -48%) diabetic patients. The mean glomerular filtration rate increased by 21% (112 +/- 12 mL/min v 135 +/- 14 mL/min) and by 23% (106 +/- 12 mL/min v 130 +/- 14 mL/min) in type I and type II diabetic patients, respectively. No significant changes were found in renal plasma flow rates or in serum concentrations of beta 2-microglobulin. With the exception of a significant (P < 0.05) reduction in hemoglobin A1 concentration in type II diabetic patients after 3 months of treatment with nitrendipine, fasting blood glucose, hemoglobin A1, residual beta-cell function (C-peptide levels), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index remained essentially unchanged during follow-up. These findings suggest that 12 months of monotherapy with the dihydropyridine-type calcium antagonist nitrendipine reduced albuminuria and increased the lowered glomerular filtration rate without adverse effects on glucose and lipid control.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nephroprotective effects of nitrendipine in hypertensive type I and type II diabetic patients. 850 36

Transgenic mice expressing growth hormone genes have been shown to have kidney lesions resembling those found in human diabetic patients. However, transgenic mice expressing a growth hormone antagonist gene have normal kidneys. In this study, streptozotocin was used to induce diabetes in growth hormone or growth hormone antagonist transgenic mice and total glycated hemoglobin levels were determined. We found streptozotocin treatment resulted in a significant increase in glycated hemoglobin levels in these animals. Despite comparable levels of glycemia and glycated hemoglobin, severe glomerulosclerosis was found in diabetic and nondiabetic growth hormone transgenic mice; moderate glomerulosclerosis was seen in diabetic nontransgenic mice; and normal glomeruli were seen in diabetic and non-diabetic growth hormone antagonist transgenic mice as well as non-diabetic nontransgenic littermates. These results suggest that growth hormone is playing a role in diabetic nephropathy, and elevated levels of growth hormone can directly affect the kidneys independent of the levels of glucose and glycated hemoglobin.
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PMID:A growth hormone antagonist protects mice against streptozotocin induced glomerulosclerosis even in the presence of elevated levels of glucose and glycated hemoglobin. 889 92

Tight metabolic control as assessed by estimation of glycated hemoglobin or albumin seems to be the main prophylactic factor in the prevention of most diabetic complications. By regular monitoring of the kidney size, GFR, and urinary albumin excretion, detection of early (reversible) diabetic nephropathy is possible. By appropriate dietary (protein restriction) and pharmacological (ACEI, antihypertensive drugs) treatment development of overt diabetic nephropathy may be prevented or markedly slowed.
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PMID:Biochemical monitoring of diabetic patients. 890 15

Glomerular hyperfiltration has been proposed as an independent risk factor for the development of diabetic nephropathy in patients with IDDM. In a case-controlled prospective study of IDDM patients without albuminuria, serial glomerular filtration rate (GFR) measurements were performed over an observation period of 10 years. A group of 25 IDDM patients (20 men, 5 women; initial age, 29 [17-49] years) with glomerular hyperfiltration (GFR >135 ml x min(-1) x 1.73 m(-2)) were matched for age, sex, and duration of diabetes with 25 IDDM patients (20 men, 5 women; initial age, 30 [17-48] years) with glomerular normofiltration (GFR 83-135 ml x min(-1) x 1.73 m(-2)). GFR, urinary albumin excretion rate (AER), blood pressure, and glycated hemoglobin were measured at baseline and at 5, 8, and 10 years. The two groups had similar entry levels of blood pressure, AER, and glycated hemoglobin. Metabolic control was similar in the two groups during follow-up. The final GFR remained higher in the group with hyperfiltration (122 [109-135] vs. 103 [95-111] ml x min(-1) x 1.73 m(-2); P = 0.02) despite a nonsignificantly faster rate of fall of GFR compared with that of the control group (2.54 [1.20-3.88] vs. 1.50 [1.01-1.99] ml x min(-1) x year(-1); P = 0.14). A similar number of patients in each group progressed to either microalbuminuria or macroalbuminuria (n = 4 vs. n = 3) or developed hypertension (blood pressure, >160/95 mmHg; n = 3 vs. n = 4). End-of-study AER was, however, higher in the group with hyperfiltration (geometric mean [95% CI]: 18.9 [11.3-31.6] vs. 11.0 [8.1-15.0]; P = 0.05), and baseline glomerular hyperfiltration was an independent determinant of end-of-study blood pressure (P = 0.04). The strongest predictors of end-of-study AER and blood pressure were their baseline values (P < 0.04 and P < 0.01, respectively). In conclusion, levels of AER and blood pressure are the main risk factors for renal outcome, while glomerular hyperfiltration appears to play a lesser role.
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PMID:Glomerular hyperfiltration in the prediction of nephropathy in IDDM: a 10-year follow-up study. 892 58

An insertion/deletion (I/D) of the human angiotensin converting enzyme (ACE) gene is a major determinant of circulating ACE levels. Recent studies suggest that the ACE I/D polymorphism may influence the risk of developing nephropathy in patients with insulin dependent diabetes mellitus (IDDM), although the mechanism responsible for the effect is unknown. Since an early increase in glomerular filtration rate (GFR) may also be a risk factor for the development of diabetic nephropathy, we sought to determine if the ACE I/D polymorphism influenced renal hemodynamic function in patients with IDDM. Genomic DNA was obtained from 39 normotensive male and female patients with uncomplicated IDDM (mean duration 3.4 years; range 1 to 6 years), and from 20 non diabetic control subjects. The ACE I/D polymorphism was determined using the polymerase chain reaction. Subjects were divided into three groups based on their ACE genotype. Values for GFR, renal plasma flow (ERPF), filtration fraction, and renal vascular resistance were determined in both groups using classic inulin and paraaminohippurate clearance techniques. Blood glucose was maintained between 4 to 6 mmol/liter in the patients with IDDM using a modified euglycemic clamp technique. Mean values for GFR were significantly greater in patients homozygous for the I allele (143 +/- 7 ml/min/1.73 m2) compared to patients homozygous for the D allele (121 +/- 3 ml/min/1.73 m2, P < 0.01), while the mean GFR values for the heterozygous patients were intermediate. ERPF was also significantly greater in patients homozygous for the I allele (850 +/- 103 ml/min/1.73 m2) compared to patients homozygous for the D allele (672 +/- 31 ml/min/1.73 m2, P < 0.04), while there were no differences in the values for mean arterial pressure, glycosylated hemoglobin, or albumin excretion rates amongst the groups. There was no dominant effect of the ACE gene I/D polymorphism in the control group. These results suggest that: (1) the ACE gene I/D polymorphism influences glomerular filtration and renal plasma flow rates in patients with early uncomplicated IDDM; and (2) differences in renal hemodynamic function do not appear to explain the protection against the development of diabetic nephropathy offered by the I allele.
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PMID:Angiotensin converting enzyme gene polymorphism and renal hemodynamic function in early diabetes. 899 25


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