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  • 1
    Electronic Resource
    Electronic Resource
    Prevalence of micro- and macroalbuminuria, arterial hypertension, retinopathy and large vessel disease in European Type 2 (non-insulin-dependent) diabetic patients (1991)
    Springer
    Diabetologia 34 (1991), S. 655-661 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; microalbuminuria ; macroalbuminuria ; arterial hypertension ; retinopathy ; macroangiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence of micro- and macroalbuminuria was determined in Type 2 (non-insulin-dependent) diabetic patients, less than 76 years of age, attending a diabetic clinic during 1987. All eligible patients (n=557) were asked to collect a 24-h urine sample for quantitative albumin analysis. Urine collections were obtained in 296 males and 253 females (96%). Normoalbuminuria were defined as urinary albumin excretion≤30 mg/24 h (n=323), microalbuminuria as 31–299 mg/24 h (n=151), and macroalbuminuria as ≥300 mg/ 24 h (n=75). The prevalence of macroalbuminuria was significantly higher in males (20%) than in females (6%), while the prevalence of microalbuminuria was almost identical in males (26%) and females (29%). The prevalence of arterial hypertension increased with increased albuminuria, being 48%, 68%, and 85% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of proliferative retinopathy rose with increasing albuminuria, being 2%, 5% and 12% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. Prevalence of coronary heart disease, based on Minnesota coded electrocardiograms, was more frequent in patients with macroalbuminuria (46%) compared to patients with microalbuminuria (26%) and patients with normoalbuminuria (22%). Foot ulcers were more frequent in micro- and macroalbuminuric patients, being 13% and 25%, respectively, compared to 5% in patients with normoalbuminuria. This cross-sectional study has revealed a high prevalence of microalbuminuria (27%) and macroalbuminuria (14%) in Type 2 diabetic patients. Patients with raised urinary albumin excretion are characterized by obesity, elevated haemoglobin Alc, increased frequency of arterial hypertension, proliferative retinopathy, coronary heart disease and foot ulcers. Thus, these findings suggest that urinary excretion of albumin should be monitored routinely in patients with Type 2 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400995
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  • 2
    Electronic Resource
    Electronic Resource
    The course of kidney function in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy (1993)
    Springer
    Diabetologia 36 (1993), S. 1071-1078 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; diabetic nephropathy ; kidney function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We evaluated the impact of some putative progression promoters on kidney function in albuminuric Type 2 (non-insulin-dependent) diabetic patients with biopsyproven diabetic glomerulosclerosis. Twenty-six patients (1 female) with a mean age of 52 (standard error 2) years and a known mean duration of diabetes of 9 (1) years were followed-up prospectively for a mean of 5.2 (range 1.0–7.0) years. Twenty-one patients received antihypertensive treatment. During the observation period the glomerular filtration rate decreased from 83 (24–146) to 58 (2–145) ml·min−1·1.73 m−2 (mean (range)) (p〈0.001). The mean rate of decline in glomerular filtration rate was 5.7 (−3.5 to 22.0) ml/min per year. Albuminuria increased from 1.2 (0.3–7.2) to 2.3 (0.4–8.0) g/24 h (geometric mean (range)) (p〈0.001). Arterial blood pressure remained unchanged: 162/93 (SE 4/3) and 161/89 (4/2) mm Hg. Univariate analysis showed the rate of decline in glomerular filtration rate to correlate with systolic blood pressure (r=0.71,p〈0.001), mean blood pressure (r=0.56,p〈0.005), albuminuria (r=0.58,p〈0.005) and the initial glomerular filtration rate (r=−0.49,p〈0.02). The rate of decline in glomerular filtration rate did not correlate significantly with dietary protein intake, total cholesterol, high-density lipoprotein cholesterol or HbA1c. Three patients died from uraemia and four patients died from cardiovascular disease. Two patients required renal replacement therapy at the end of the observation period. Our prospective observational study revealed that one-fifth of the patients developed end-stage renal failure during the 5-year observation period. The decline in glomerular filtration rate varied considerably between patients. Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy. Elevated systolic blood pressure accelerates the progression of diabetic nephropathy in Type 2 diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374501
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  • 3
    Electronic Resource
    Electronic Resource
    Glomerular size- and charge selectivity in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy (1994)
    Springer
    Diabetologia 37 (1994), S. 195-201 
    Details
    ISSN: 1432-0428
    Keywords: Key words Type 2 (non-insulin-dependent) diabetes mellitus, diabetic nephropathy, IgG, IgG4, IgG/albumin selectivity index, IgG/IgG4 selectivity index.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In an attempt to evaluate the mechanisms of proteinuria in diabetic kidney disease, we measured the renal clearances of albumin, total IgG, and IgG4 in 20 male Type 2 (non-insulin-dependent) diabetic patients with diabetic glomerulosclerosis (biopsy proven), in 10 male Type 2 diabetic patients without nephropathy (urinary albumin excretion rate ≤ 30 mg/24 h), and in 10 healthy male subjects. The fractional clearance of albumin was increased in patients with nephropathy: 659 (42–4355) · 10–6 (median (range)), compared to 2.6 (0.2–14.2) · 10–6 in patients without nephropathy, and 2.3 (0.4–4.2) · 10–6 in healthy subjects. The fractional clearance of total IgG (neutral) and of IgG4 (anionic) was 40–50 times higher in patients with nephropathy compared to the two other groups. The IgG/IgG4 selectivity index was not significantly different in the three groups, being: 1.12 (0.06–5.65), 1.16 (0.45–3.72) and 1.35 (0.65–3.34) in patients with nephropathy, patients without nephropathy, and healthy subjects, respectively. The IgG/albumin selectivity index was decreased in patients with nephropathy: 0.27 (0.01–1.26) compared to 1.29 (0.07–2.67) (p〈0.05) and 1.23 (0.76–7.84) (p〈0.001) in patients without nephropathy and healthy subjects, respectively. No significant change in IgG/albumin selectivity index was observed between patients without nephropathy and healthy subjects. The systolic blood pressure was elevated in the patients with nephropathy: 164±21 mm Hg (mean ± SD) compared to patients without nephropathy: 145±20 mm Hg (p〈0.05) and to healthy subjects: 133±19 mm Hg (p〈0.005). The diastolic blood pressure was higher in patients with and without nephropathy: 92±7 vs 90±10 mm Hg compared to 79±8 mm Hg (p〈0.005) in healthy subjects. Our cross-sectional study suggests that impaired barrier size selectivity, probably due to an increase in large pore area (“shunt pathway”) in the glomerular capillary wall and systemic hypertension are the major pathogenic mechanisms of proteinuria in Type 2 diabetic patients with diabetic nephropathy. [Diabetologia (1994) 37: 195–201]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050093
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of insulin on renal sodium handling in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetic patients with peripheral insulin resistance (1991)
    Springer
    Diabetologia 34 (1991), S. 275-281 
    Details
    ISSN: 1432-0428
    Keywords: Glomerular filtration rate ; lithium clearance ; sodium excretion ; potassium excretion ; isoglycaemic clamp ; insulin infusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sodium retaining effect of insulin was studied in ten Type 2 (non-insulin-dependent) diabetic patients (mean age 56 (43–73) years, mean body mass index 29.5 (24.2–33.7) kg/m2) and eight age-matched control subjects (mean age 57 (43–68) years, mean body mass index 23.4 (20.8–26.6) kg/m2). The renal clearances of 99mTc-DTPA, lithium, sodium and potassium were measured over a basal period of 90 min. Then insulin was infused at a rate of 40 mU·mirr−1·m−2. After an equilibration period of 90 min, the clearance measurements were repeated during a new 90 min period. Blood glucose was clamped at the basal level (diabetic patients: 9.9±3.5, control subjects: 5.3±0.5 mmol/l) by a variable glucose infusion. Basal plasma insulin concentration was elevated in the diabetic patients (0.12±0.05 vs 0.05±0.02 pmol/ml, p〈0.01). Insulin infusion resulted in comparable absolute increments in plasma insulin concentrations in the diabetic group and in the control group (0.44±0.13 vs 0.36±0.07 pmol/ml, NS). The metabolic clearance rate of glucose during the last 30 min of insulin infusion was lower in the diabetic patients (155±62 vs 320±69 ml·min−1·m2, p〈0.01), reflecting peripheral insulin resistance. The decline in sodium clearance during insulin infusion was similar in diabetic subjects (1.8±1.1 vs 0.7±0.4 ml·min−1·1.73 m−2, p〈 0.01) and in control subjects (1.7±0.3 vs 0.8±0.3 ml · min−1 · 1.73 m−2, p〈0.01). The glomerular filtration rate and lithium clearance was unchanged, consequently calculated distal tubular fractional sodium reabsorption increased (diabetic patients: 92.9±4.1 vs 97.1±1.5, p〈0.01, control subjects: 93.1±1.1 vs 96.5±0.6%, p〈 0.01). Estimated extracellular fluid volume was 10% higher in the diabetic subjects (16.3±2.1 vs 14.8±2.01·1.73 m−2, NS). In conclusion, the sodium retaining effect of insulin is preserved in Type 2 diabetic patients with peripheral insulin resistance. Insulin may contribute to sodium and fluid retention and thus to the increased frequency of hypertension in hyperinsulinaemic Type 2 diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405088
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  • 5
    Electronic Resource
    Electronic Resource
    Apolipoprotein(a) and cardiovascular disease in Type 2 (non-insulin-dependent) diabetic patients with and without diabetic nephropathy (1993)
    Springer
    Diabetologia 36 (1993), S. 438-444 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; diabetic nephropathy ; apolipoprotein(a) ; cardiovascular disease ; lipid metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The relative mortality from cardiovascular disease is on average increased five-fold in Type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy compared to non-diabetic subjects. We assessed the possible contribution of dyslipidaemia in general and elevated serum apolipoprotein(a) (apo(a)) in particular. Type 2 diabetic patients with normo-, micro- and macroalbuminuria were compared with healthy subjects. Each group consisted of 37 subjects matched for age, sex and diabetes duration. Serum creatinine in the nephropathy group was 105 (54–740) Μmol/l. The prevalence of ischaemic heart disease (resting ECG, Minnesota, Rating Scale) was 57, 35, 19 and 2% in macro-, micro- and normoalbuminuric diabetic patients and healthy subjects, respectively. The prevalence of ischaemic heart disease was higher in all diabetic groups as compared to healthy subjects (p〈0.05), and higher in macroalbuminuric as compared to normoalbuminuric diabetic patients (p〈0.01). There was no significant difference between apo(a) in the four groups: 161 (10–1370), 191 (10–2080), 147 (10–942), 102 (10–1440) U/l (median (range)) in macro-, micro- and normoalbuminuric groups and healthy subjects. Serum total-cholesterol, HDL-cholesterol and LDL-cholesterol were not significantly different when comparing healthy subjects and each diabetic group. Apolipoprotein A-I was lower (p〈0.05) in all diabetic groups as compared to healthy subjects (nephropathy vs healthy subjects): 1.50±0.25 vs 1.69±0.32 g/l (mean ± SD). Triglyceride was higher (p〈0.05) in patients with nephropathy and microalbuminuria as compared to healthy subjects (nephropathy vs healthy subjects): 2.01 (0.66–14.7) vs 1.09 (0.41–2.75) mmol/l (median (range)). Apolipoprotein B was higher (p〈0.02) in patients with nephropathy as compared to the other three groups (nephropathy vs healthy subjects): 1.54±0.47 vs 1.33±0.30 g/l. In conclusion, our case-control study has confirmed that Type 2 diabetic patients with increased urinary albumin excretion frequently suffer from dyslipidaemia and cardiovascular disease. However, our study revealed no significant elevation in serum concentration of apo(a) in patients with diabetic nephropathy, but numbers were small.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402281
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  • 6
    Electronic Resource
    Electronic Resource
    Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy (1992)
    Springer
    Diabetologia 35 (1992), S. 447-451 
    Details
    ISSN: 1432-0428
    Keywords: Plasma lipoproteins ; albuminuria ; diabetic nephropathy ; glomerular filtration rate ; Type 1 (insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to assess the effect of simvastatin on plasma lipoproteins and renal function in hypercholesterolaemic Type 1 (insulin-dependent) diabetic patients with diabetic nephropathy. Twenty-six hypercholesterolaemic (total cholesterol ≽ 5.5 mmol/l) Type 1 diabetic patients with nephropathy were enrolled in a double-blind randomized placebo-controlled study for 12 weeks. The active treatment group (n -14) received simvastatin (10–20 mg/day) for 12 weeks while the remaining 12 patients received treatment with placebo. The results during simvastatin treatment (baseline vs 12 weeks): total cholesterol 6.6 vs 4.8 mmol/1 (p 〈 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p 〈 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p 〈 0.01). HDL-cholesterol, and apolipoprotein A-I remained unchanged. Total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A–I, apolipoprotein B remained unchanged during placebo treatment. Albuminuria measured during the simvastatin and the placebo treatment (baseline vs 12 weeks) (the data are logarithmically transformed before analysis because of their positively skewed transformation; geometric mean (×/÷ antilog SE) is indicated) was 458 (×/÷ 1.58) vs 393 (×/÷ 1.61) and 481 (×/÷ 1.62) vs 368 (×/÷ 1.78 μg/min (NS). Glomerular filtration rate during simvastatin and placebo treatment (baseline vs 12 weeks) was 64 vs 63 and 72 vs 74 ml·min−1·1.73 m−2, respectively. Two patients receiving simvastatin treatment were withdrawn, one due to gastrointestinal side effects and one due to myalgia. In conclusion, our short-term study in Type 1 diabetic patients with diabetic nephropathy did not reveal any beneficial effect on albuminuria despite a striking lipid-lowering effect of simvastatin in diabetic nephropathy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02342442
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  • 7
    Electronic Resource
    Electronic Resource
    Glomerular structure and function in proteinuric Type 2 (non-insulin-dependent) diabetic patients (1993)
    Springer
    Diabetologia 36 (1993), S. 1064-1070 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; diabetic nephropathy ; diabetic glomerulopathy ; basement membrane ; mesangium ; mesangial matrix ; glomerular hypertrophy ; glomerular occlusion ; stereology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glomerular ultrastructure was examined in a series of 20 Type 2 (non-insulin-dependent) diabetic patients with proteinuria. Reference was made to data previously obtained in non-diabetic kidney donors and in Type 1 (insulindependent) diabetic patients with similar degrees of proteinuria. The Type 2 diabetic patients demonstrated the changes which characterize the diabetic glomerulopathy seen in Type 1 diabetic patients: basement membrane thickening, and increase in the mesangium and mesangial matrix expressed as fraction of the glomerular volume. Among the Type 2 diabetic patients there was more variation then among the Type 1 diabetic patients, as this group included subjects with normal parameters. The group means and coefficients of variation (=SD/mean) of the glomerulopathy parameters combined in the glomerulopathy index=basement membrane thickness/10+Vv(matrix/glom)·100 were 81 (0.30) and 92 (0.15) in the two diabetic groups, clearly different from the non-diabetic index, 42 (0.16). All Type 2 diabetic patients who also had retinopathy had a glomerulopathy index above the normal range. Similar changes in glomerular composition were seen in the two diabetic groups: with increasing glomerulopathy the volume of matrix dominated over the peripheral basement membrane, and a shift in the ratio of interfaces was seen: mesangial surface towards capillary lumen increased relative to the urinary surface, and peripheral capillary surface comprised less of the total capillary surface. Data indicated marked glomerular hypertrophy, which correlated with the mesangial volume fraction, thus encompassing preserved filtration surface per glomerulus. An inverse correlation obtained between the index of glomerulopathy and current glomerular filtration rate, as well as the ensuing rate of decline in glomerular filtration rate, as well as the ensuing rate of decline in glomerular filtration rate: (index (glomerulopathy) vs rate of decline in glomerular filtration rater=0.84,p〈0.0001). No correlation was found between glomerular volume and the ensuing rate of decline in glomerular filtration rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374500
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  • 8
    Electronic Resource
    Electronic Resource
    Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy (1996)
    Springer
    Diabetologia 39 (1996), S. 1590-1597 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Non-insulin-dependent diabetes mellitus ; diabetic microangiopathy ; diabetic nephropathy ; capillary permeability ; endothelium ; haemodynamics ; cardiovascular disease.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The Steno hypothesis suggests that albuminuria reflects widespread vascular damage (proliferative retinopathy and severe macroangiopathy) due to a generalized vascular (endothelial) dysfunction. We assessed this concept in NIDDM (non-insulin-dependent diabetic) patients with (13 female/39 male, age 60 ± 7 years, group 1) and without (12 female/41 male, age 61 ± 7 years, group 2) diabetic nephropathy compared to matched non-diabetic subjects (7 female/15 male, age 58 ± 8 years, group 3). A 12-lead ECG was recorded and coded blindly using the Minnesota Rating Scale; the World Health Organization cardiovascular questionnaire was used to assess past and present evidence of myocardial infarction, angina pectoris, stroke, and peripheral vascular disease (digital systolic blood pressure determination). The degree of diabetic retinopathy was scored from fundus photography. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), plasma concentrations of prorenin (radioimmunoassay) and serum concentrations of von Willebrand factor (enzyme-linked immunoadsorbent assay). Prevalence of ischaemic heart disease (ECG reading) (49/20/5)% and peripheral vascular disease as indicated by reduced systolic blood pressure on big toe (69/30/14)% was significantly higher in group 1 vs group 2 (p 〈 0.01) and in group 2 vs group 3 (p 〈 0.01), respectively. The prevalence and severity of retinopathy was higher in group 1 vs 2 (p 〈 0.01). Transcapillary escape rate of albumin (%/h) was elevated in group 1 and 2 as compared to control subjects: 7.9 (4.3–13.7); 7.4 (3.7–16.4) vs 6.0 (3.4–8.7), (p 〈 0.005), respectively. Plasma prorenin activity (IU/ml) was raised in group 1 and group 2 as compared to group 3: 272 (59–2405); 192 (18–813), and 85 (28–246), p 〈 0.001, respectively. Serum von Willebrand factor (IU/ml)was elevated in group 1 as compared to group 2 and 3: 2.07 (0.83–4.34); 1.60 (0.30–2.99) and 1.50 (1.00–2.38), p 〈 0.001, respectively. Our study demonstrated that NIDDM patients with and without albuminuria had increased transcapillary escape of albumin and raised prorenin activity, whereas only those with albuminuria had increased von Willebrand factor. Patients with NIDDM may have abnormal endothelial function in the absence of albuminuria. [Diabetologia (1996) 39: 1590–1597]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050619
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