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  • 1
    ISSN: 1432-0428
    Keywords: IDDM ; diabetic nephropathy ; microalbuminuria ; proteinuria ; lipid metabolism ; small dense LDL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To answer the question whether the elevation of LDL-cholesterol in IDDM patients with incipient and established diabetic nephropathy is accompanied by changes in LDL size or composition, we studied distribution of LDL particles in 57 normoalbuminuric [AER 7 (1–19) μg/min, median and range], in 46 microalbuminuric [AER 50 (20–192) μg/min] and in 33 proteinuric [AER 422 (233–1756) μg/min] IDDM patients as well as in 49 non-diabetic control subjects with normoalbuminuria. The three diabetic groups were matched for duration of diabetes and glycaemic control. The mean particle diameter of the major LDL peak was determined by nondenaturing gradient gel electrophoresis. Composition and density distribution of LDL were determined in the subgroups of each patient group by density gradient ultracentrifugation. Normoalbuminuric IDDM patients had larger LDL particles than non-diabetic control subjects (260 Å vs 254 Å, p〈0.05). LDL particle diameter was inversely correlated with serum triglycerides in all groups (p〈0.05 for normoalbuminuric and p〈0.001 for other groups). Triglyceride content of LDL was higher in three IDDM groups compared to control group (p〈0.05). The elevation of LDL mass in microalbuminuric and proteinuric IDDM groups compared to normoalbuminuric IDDM group (p〈0.05 for both) was mainly due to the increment of light LDL (density 1.0212–1.0343 g/ml). There were no significant changes in the density distribution or composition of LDL between the three diabetic groups. In conclusion the increase of LDL mass without major compositional changes suggests that the elevation of LDL in incipient and established diabetic nephropathy is primarily due to the increased number of LDL particles. The prevalence of atherogenic small dense LDL particles in IDDM patients with microalbuminuria and proteinuria is closely dependent on plasma triglyceride concentration.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate ( 〈 15 μg/min) and 16 with microalbuminuria (15–200 μg/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p = 0.27). The tissue was sectioned systematically, 1-μm thick sections for light microscopy at 10-μm intervals, and thin sections for electron microscopy taken at 60-μm intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500 × ), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p = 0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p = 0.0004) and matrix-T , expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) μm vs 1.44 (0.30) μm (p = 0.004), and 1.62 (0.28) μm vs 1.03 (0.34) (p = 0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T . In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy. [Diabetologia (1995) 38: 1320–1327]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hyalinization of juxtaglomerular arterioles is prominent in advanced diabetic nephropathy and may have important functional consequences. We studied the early stages of diabetic renal disease using kidney biopsy material from insulin-dependent diabetic patients, 8 with normal albumin excretion rate (〈15 Μ/min) and 16 with microalbuminuria (15–200 Μg/min). Ten living non-diabetic kidney donors served as a control group. Median duration of diabetes was 9.5 years (range 5–31) in patients with normoalbuminuria, and 12 years (7–22) in patients with microalbuminuria (p=0.27). The tissue was sectioned systematically, 1-Μm thick sections for light microscopy at 10-Μm intervals, and thin sections for electron microscopy taken at 60-Μm intervals. The arterioles were identified as afferent or efferent, and total profiles were photographed (magnification 7500×), providing a systematic independent sample for measurements using standard stereological methods. Patients with microalbuminuria had significantly increased arteriole parameters compared with the control group: for afferent and efferent arterioles the volume fraction of matrix/media, means and (coefficient of variation, CV), was 0.47 (0.16) vs 0.33 (0.19) (p=0.0009), and 0.62 (0.14) vs 0.45 (0.23) (p=0.0004) and matrix-T, expressing amount of matrix per unit arteriolar surface, 2.38 (0.38) Μm vs 1.44 (0.30) Μm (p=0.004), and 1.62 (0.28) Μm vs 1.03 (0.34) (p=0.0009). Patients with normoalbuminuria showed no significant differences from the control group, and had lower values than microalbuminuric patients for all parameters except the afferent matrix-T. In the normoalbuminuric group a correlation was found between parameters for afferent arterioles and those for glomerular structure. In conclusion there is arteriolar accumulation of extracellular material in the early phase of diabetic nephropathy, concomitant with early glomerulopathy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Key words Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p 〈 0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p 〈 0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p 〈 0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r = 0.65, p 〈 0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients. [Diabetologia (1995) 38: 1197–1204]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent-diabetes mellitus ; diabetic nephropathy ; diabetic retinopathy ; blood pressure ; albumin excretion rate.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46 %) and without (54 %) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal ( 〈 20 μg/min) below median diastolic pressure (75 mm Hg) and increased steeply (p 〈 0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk. [Diabetologia (1995) 38: 599–603]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Insulin-dependent-diabetes mellitus ; diabetic nephropathy ; diabetic retinopathy ; blood pressure ; albumin excretion rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (〈20 Μg/min) below median diastolic pressure (75 mm Hg) and increased steeply (p〈0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus ; cardiovascular disease ; microalbuminuria ; autonomic neuropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-dependent diabetic (IDDM) subjects with microalbuminuria have an increased long-term risk of overt cardiovascular disease; however, the early exposure to cardiovascular risk factors may increase their predisposition to current silent myocardial ischaemia. The frequency of silent myocardial ischaemia detected by stress echocardiography and electrocardiography was significantly greater in 32 asymptomatic IDDM patients with microalbuminuria compared to 32 normoalbuminuric IDDM patients (25 % [n = 8] vs 6.3 % [n = 2]; p = 0.03, odds ratio [95 % CI] 6.3 [1.2, 37.8]). Elective coronary artery bypass grafting was required in 1 patient with microalbuminuria and silent myocardial disease. Microalbuminuria and poorer autonomic function were independently associated with silent myocardial ischaemia in multivariate analysis (p = 0.03 and p = 0.02, respectively). Screening for silent myocardial ischaemia using these non-invasive tests may be warranted in microalbuminuric IDDM which patients could be of considerable clinical importance. [Diabetologia (1996) 39: 854–856]
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetic nephropathy is associated with functional changes in the glomerular filtration barrier but the structural counterpart remains unknown. Width of glomerular epithelial cell foot processes and of filtration slits were determined by morphometric methods in 11 non-diabetic kidney donors and in 28 diabetic patients with albumin excretion rates ranging from normal to proteinuria. Foot process width was estimated from the ratio of tuft surface density to length density of slits. At high magnification independently sampled, perpendicularly cut slits were classified. Foot process width on peripheral basement membrane was increased in microalbuminuric compared to normoalbuminuric diabetic patients (p〈0.05) but showed no significant correlation with the level of albumin excretion when patients with increased barrier permeability were considered. Width of filtration slits in normo- and microalbuminuric diabetic patients exceeded that in non-diabetic control subjects (p〈0.05). Filtration slits were narrower in patients with overt proteinuria than in patients with microalbuminuria (p〈0.05) and correlated with glomerular filtration rate in all of the diabetic patients (r=0.65, p〈0.005). The results show that insulin-dependent diabetic patients with nephropathy present changes of epithelial cells and filtration slits, demonstrable already in the stage of microalbuminuria. The mechanism of albumin leakage is not achieved by these measures. The dimension of filtration slits may play a contributing role in the level of glomerular filtration rate in diabetic patients.
    Type of Medium: Electronic Resource
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