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  • 1
    Digitale Medien
    Digitale Medien
    A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro-and normoalbuminuria (1995)
    Springer
    Diabetologia 38 (1995), S. 1320-1327 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Key words Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00401765
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  • 2
    Digitale Medien
    Digitale Medien
    High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria (1997)
    Springer
    Diabetologia 40 (1997), S. 1191-1196 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Keywords Insulin-dependent diabetes mellitus ; proteinuria ; insulin resistance ; hyperlipidaemia ; cardiovascular disease.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER 〉 45 μg/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER 〈 20 μg/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20 % for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 ± 10 vs 70 ± 14 years; p 〈 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8 %; odds ratio 3.96, 95 % CI 1.3 to 12.2; p 〈 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14 % p 〈 0.01) and hyperlipidaemia (49 vs 26 % p 〈 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1–107) vs 15.6 (0.2–98) mg/dl; p 〈 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) Kitt index: 3.7 (0.7–6.2) vs 4.8 (0.7–6.7)% per min; p 〈 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy. [Diabetologia (1997) 40: 1191–1196]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250050806
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  • 3
    Digitale Medien
    Digitale Medien
    A quantitative ultrastructural study of juxtaglomerular arterioles in IDDM patients with micro- and normoalbuminuria (1995)
    Springer
    Diabetologia 38 (1995), S. 1320-1327 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Diabetic nephropathy ; diabetic glomerulopathy ; arteriolar hyalinosis ; juxtaglomerular arterioles ; extracellular matrix ; microalbuminuria ; stereology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00401765
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  • 4
    Digitale Medien
    Digitale Medien
    Premature cell ageing and evolution of diabetic nephropathy (1997)
    Springer
    Diabetologia 40 (1997), S. 244-246 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Keywords Cell ageing ; nephropathy ; glycaemic control ; fibroblasts ; glomerular filtration rate.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The rate of development and progression of renal disease varies greatly in insulin-dependent diabetic (IDDM) patients. The cellular and molecular reasons for this difference are largely unknown but could be related to early cell differentiation, a phenomenon recently reported in IDDM patients with nephropathy. In this study we compared cell differentiation and cell volume between IDDM patients with and without nephropathy and investigated the cell ageing characteristics in relation to the rate of evolution of renal disease in the IDDM patients with diabetic nephropathy. Cell volume was larger and the percentage of post-mitotic fibrocytes was higher in skin fibroblasts derived from IDDM patients with diabetic nephropathy compared to those from IDDM patients without kidney disease (mean ± SD in arbitrary units 817.3 ± 25.7 vs 760 ± 32.8; p = 0.005; and mean ± SD % 33.6 ± 11.8 vs 20.8 ± 10; p = 0.02 respectively). Analysis of the interaction of the time to proteinuria (TTP) and the rate of change of glomerular filtration rate (GFR) with glycaemic control, arterial blood pressure and cell volume and the state of cell differentiation showed that glycated haemoglobin and the percentage of post-mitotic fibrocytes were negatively correlated to TTP (r = – 0.68; p = 0.008; r = – 0.52; p = 0.05 respectively) and positively associated with the rate of change of GFR (r = 0.76; p = 0.03; r = 0.56; p = 0.037 respectively). Cell volume was negatively correlated to TTP (r = – 0.53; p = 0.05). Diastolic blood pressure was also related to the rate of GFR change (r = 0.56; p = 0.039). In a multiple linear regression analysis glycated haemoglobin maintained its significant independent relationship with TTP at the 1 % level, while the strength of the association between the percentage of post-mitotic cells and cell volume was reduced to the 11 and 9 % level, respectively. Cultured skin fibroblasts from IDDM patients with nephropathy show signs of early differentiation. Glycaemic control is a key factor in the rate of onset of proteinuria and different rates of cell ageing appear to contribute to the rate of development and progression of diabetic nephropathy. Their interaction may be responsible for the severity of renal involvement in susceptible IDDM patients. [Diabetologia (1997) 40: 244–246]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250050670
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  • 5
    Digitale Medien
    Digitale Medien
    Glomerular epithelial foot processes and filtration slits in IDDM patients (1995)
    Springer
    Diabetologia 38 (1995), S. 1197-1204 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Key words Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00422369
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  • 6
    Digitale Medien
    Digitale Medien
    Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM (1996)
    Springer
    Diabetologia 39 (1996), S. 60-69 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Cytokines ; T helper subsets ; interleukin-2 ; interferon-γ ; interleukin-1 ; tumour necrosis factor ; prediabetes ; identical twins
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-γ), T helper 2 (interleukin-4 and inter-leukin-10) lymphocytes and macrophages (tumour necrosis factor-α, interleukin-1 α and interleukin-1 Β) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-γ, tumour necrosis factor-α and interleukin-1 α than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p〈0.05 for all). Compared with control subjects, patients with long-standing IDDM and those with NIDDM had higher interleukin-2 and tumour necrosis factor-α levels (p〈0.01 for all). Interleukin-4 and interleukin-10 were detectable in sera of patients with Graves' disease only, while interleukin-1 Β was not detectable in the serum of any control or test subject. To investigate whether high cytokine levels precede the onset of IDDM, we studied 28 non-diabetic identical co-twins of patients with IDDM, followed-up prospectively for up to 6 years after the diagnosis of the index. Levels of tumour necrosis factor-α and interleukin-1 α were elevated above the normal range more frequently in the eight twins who developed diabetes than in those 20 who did not (p〈0.005). Analysis of T helper 1 and T helper 2 profiles of the twin groups did not reveal a clear difference between prediabetic twins and twins remaining non-diabetic. These results support the notion that T helper 1 lymphocytes may play a role in the development of IDDM. This is associated with release of macrophage-derived cytokines, which is also a feature of the prediabetic period. The lack of evidence of a dominant T helper 1 profile of cytokine release before diabetes onset suggests that additional events, activating this arm of the cellular immune response, are required in the immediate prediabetic period.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00400414
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  • 7
    Digitale Medien
    Digitale Medien
    Blood pressure, retinopathy and urinary albumin excretion in IDDM: the EURODIAB IDDM Complications Study (1995)
    Springer
    Diabetologia 38 (1995), S. 599-603 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Key words Insulin-dependent-diabetes mellitus ; diabetic nephropathy ; diabetic retinopathy ; blood pressure ; albumin excretion rate.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250050325
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  • 8
    Digitale Medien
    Digitale Medien
    Blood pressure, retinopathy and urinary albumin excretion in IDDM: the EURODIAB IDDM Complications Study (1995)
    Springer
    Diabetologia 38 (1995), S. 599-603 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Insulin-dependent-diabetes mellitus ; diabetic nephropathy ; diabetic retinopathy ; blood pressure ; albumin excretion rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00400730
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  • 9
    Digitale Medien
    Digitale Medien
    Microalbuminuria as a marker of silent myocardial ischaemia in IDDM patients (1996)
    Springer
    Diabetologia 39 (1996), S. 854-856 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Keywords Insulin-dependent diabetes mellitus ; cardiovascular disease ; microalbuminuria ; autonomic neuropathy.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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]
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001250050520
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  • 10
    Digitale Medien
    Digitale Medien
    Glomerular epithelial foot processes and filtration slits in IDDM patients (1995)
    Springer
    Diabetologia 38 (1995), S. 1197-1204 
    Details
    ISSN: 1432-0428
    Schlagwort(e): Albuminuria ; diabetic glomerulopathy ; diabetic nephropathy ; filtration slits ; glomerular epithelial cells ; stereology
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00422369
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