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  • 1
    Electronic Resource
    Electronic Resource
    Epidemiology of renal involvement in newly-diagnosed middle-aged and elderly diabetic patients. Cross-sectional data from the population-based study “Diabetes Care in General Practice”, Denmark (1993)
    Springer
    Diabetologia 36 (1993), S. 1007-1016 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic nephropathies ; Type 2 (non-insulin-dependent) diabetes mellitus ; epidemiology ; family practice ; smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report on a study in which 487 Danish general practitioners participated with the purpose of including all newly-diagnosed diabetic patients aged 40 years or more from a well-defined catchment population during a welldefined time period. A, total of 1267 diabetic patients with a median age of 65.3 years were included. Renal involvement was assessed from the albumin/creatinine ratio in a morning urine sample. Albumin/creatinie ratio was 〈2/2〈20/≥20 mg/mmol in 59.8/33.6/6.6% of male and 66.6/28.8/4.6% of female patients. The level of albumin/creatinine ratio increased with age and the observed overall male predominance was almost confined to diabetic patients with an albumin/creatinine ratio of 5 mg/mmol or greater. By taking into account the confounding effect of age and sex, a positive association between smoking and albumin/creatinine ratio was disclosed. Moreover, high systolic blood pressure, hypertriglyceridaemia, hypercholesterolaemia (males only) and high HbA1c, but not body mass index or diastolic blood pressure were identified as correlates of elevated albumin/creatinine ratio. Glucosuria was positively correlated with albumin/creatinine ratio even when the influence of HbA1c, sex and age was taken into account. A positive correlation between serum creatinine and albumin/creatinine ratio was seen in males, but not in females. In addition, renal involvement was associated with the presence of peripheral angiopathy and diabetic retinopathy and with high resting heart rate. The cross-sectional data presented highlight the importance of reducing the overall burden of modifiable risk factors in newly-diagnosed Type 2 diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374492
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  • 2
    Electronic Resource
    Electronic Resource
    Prognostic value of urinary albumin excretion rate and other risk factors in elderly diabetic patients and non-diabetic control subjects surviving the first 5 years after assessment (1993)
    Springer
    Diabetologia 36 (1993), S. 1030-1036 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; mortality ; urinary albumin excretion ; risk factors ; ischaemic heart disease ; hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 1981–1982 urinary albumin excretion rates were determined in 211 diabetic and 216 non-diabetic subjects aged 60–74 years. By April 1992 122 diabetic and 58 non-diabetic probands had died. Dividing the two study populations at an albumin excretion rate of 15 μg/min showed that 69.3% of diabetic subjects with values at or above the limit, and 49.9% of those with values below (log rank testp=0.0082) had died. The corresponding values for non-diabetic subjects were 44.4% and 21.0%, respectively (log rank testp=0.0002). In single factor log rank tests ischaemic heart disease and a low value of HDL were also predictive of death in the diabetic population during a 10–11-year observation period. In the non-diabetic population ischaemic heart disease, hypertension, and a serum creatinine level above the median value were predictive. In further log rank analyses probands dying during the first years, (e.g. the first 2 years) were removed from the calculations. The prognostic value of the above-mentioned factors diminished with time. In a Cox Regression analysis we found that the predictive value of urinary albumin excretion rate to mortality had disappeared when subjects who had died during the first 5 years were removed from the analysis, whereas HDL in the diabetic patients and blood pressure and serum creatinine in non-diabetic subjects were still of significant predictive value. We therefore conclude that urinary albumin excretion rate is a more short-term predictor of mortality than previously thought, in contrast to HDL, hypertension and serum creatinine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374495
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  • 3
    Electronic Resource
    Electronic Resource
    Renal function and insulin sensitivity during simvastatin treatment in Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria (1993)
    Springer
    Diabetologia 36 (1993), S. 1079-1086 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; microalbuminuria ; glomerular filtration rate ; plasma lipoproteins ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of simvastatin (10–20 mg/day) on kidney function, urinary albumin excretion rate and insulin sensitivity was evaluated in 18 Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria and moderate hypercholesterolaemia (total cholesterol ≥5.5 mmol·l−1). In a double-blind, randomized and placebo-controlled design treatment with simvastatin (n=8) for 36 weeks significantly reduced total cholesterol (6.7±0.3 vs 5.1 mmol·l−1 (p〈0.01)), LDL-cholesterol (4.4±0.3 vs 2.9±0.2 mmol·l−1 (p〈0.001)) and apolipoprotein B (1.05±0.04 vs 0.77±0.02 mmol·l−1 (p〈0.01)) levels as compared to placebo (n=10). Both glomerular filtration rate (mean±SEM) (simvastatin: 96.6±8.0 vs 96.0±5.7 ml·min−1·1.73 m−2, placebo: 97.1±6.7 vs 88.8±6.0 ml·min−1·1.73 m−2) (NS) and urinary albumin excretion rate (geometric mean x/÷ antilog SEM) (simvastatin: 18.4x/÷1.3vs 16.2 x/÷1.2 μg·min−1, placebo 33.1 x/÷ 1.3 vs 42.7 x/÷ 1.3 μg·min−1)(NS) were unchanged during the study. A euglycaemic hyperinsulinaemic clamp was performed at baseline and after 18 weeks in seven simvastatin-and nine placebo-treated patients. Isotopically determined basal and insulin-stimulated glucose disposal was similarly reduced before and during therapy in both the simvastatin (2.0±0.1 vs 1.9±0.1 (NS) and 3.1±0.6 vs 3.1±0.7 mg·kg−1·min−1 (NS)) and the placebo group (1.9±0.1 vs 1.8±0.1 (NS) and 4.1±0.6 vs 3.8±0.2 mg·kg−1·min−1 (NS)). No different was observed in glucose storage or glucose and lipid oxidation before and after treatment. Further, the suppression of hepatic glucose production during hyperinsulinaemia was not influenced by simvastatin (−0.7±0.8 vs −0.7±0.5 mg·kg−1·min−1 (NS)). In conclusion, despite marked improvement in the dyslipidaemia simvastatin had no impact on kidney function or urinary albumin excretion rate and did not reduce insulin resistance in these microalbuminuric and moderately hypercholesterolaemic Type 2 diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02374502
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  • 4
    Electronic Resource
    Electronic Resource
    Circadian variation of blood pressure in patients with diabetic nephropathy (1992)
    Springer
    Diabetologia 35 (1992), S. 1074-1079 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; diabetic nephropathy ; ambulatory blood pressure ; circadian ; variation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The association between diurnal blood pressure variation and diabetic nephropathy was assessed in four groups of Type 1 (insulin-dependent) diabetic patients who underwent 24-h ambulatory blood pressure monitoring using an oscillometrie technique. Patients with nephropathy, who had never been treated for hypertension (group D3,n = 13), were individually matched for age, sex and diabetes duration to a group of microalbuminuric patients (D2,n = 26), to normoalbuminuric patients (D1,n = 26) and to healthy control subjects (C,n = 26). Group D3 was also compared to patients with advanced nephropathy receiving treatment for hypertension, mainly a combination of angiotensin converting enzyme inhibitors, metoprolol and diuretics (D4,n = 11). In group D3 24-h diastolic blood pressure (85 ± 8 mm Hg) was comparable to the results obtained in D4 (85 ± 8 mm Hg) but significantly higher than in D2 (78 ± 7 mm Hg), D1 (73 ± 7 mm Hg) and C (73 ± 7 mm Hg,p 〈 0.05, Tukey's test). The night/day ratio of diastolic blood pressure was higher in D3 (86 ± 5 %) and D2 (85 ± 7%) than in C (80 ± 7 %,p 〈 0.02). This ratio was also elevated in group D4 (94 ± 8%) compared to D3 (p 〈 0.05) corresponding to a marked smoothing of the diurnal blood pressure curve. The 24-h heart rate (beats per min) was significantly elevated in D3 (84 ± 8) and D2 (80 ± 10) compared with C (73 ± 11,p 〈 0.05 Tukey's test), suggesting the presence of parasympathetic neuropathy In conclusion the normal circadian variation of blood pressure was moderately disturbed in a group of microalbuminuric patients and patients with less advanced overt nephropathy. Patients with advanced diabetic nephropathy receiving antihypertensive therapy showed a marked reduction of nocturnal blood pressure fall, which can only be identified by the application of ambulatory blood pressure measurements to verify the 24-h effectiveness of blood pressure control.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02221684
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  • 5
    Electronic Resource
    Electronic Resource
    Systolic blood pressure relates to the rate of progression of albuminuria in NIDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 1251-1258 
    Details
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; albuminuria ; blood pressure ; rate of progression ; progressors ; glycaemic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We prospectively followed a cohort of 278 non-insulin-dependent (NIDDM) patients for a 6-year period, intending to estimate the rate of increase of albuminuria and to identify clinical variables that influence this increase. At baseline, normo-albuminuria (N) was seen in 74%, microalbuminuria (M) in 19% and 7% presented with proteinuria (P). A total of 80 patients died; they were older (p〈0.001) and had higher albumin excretion both at baseline and as an average during follow-up (p〈0.01). At baseline, patients with proteinuria had higher blood pressures (systolic and diastolic), whereas there was no difference between patients with normo- and microalbuminuria. Glycaemic control was increasingly poor throughout the three groups. At follow-up, an average relative rate of increase of albuminuria (slope) of 17% per year was seen both for patients with complete 6 years, follow-up (n=135) and patients with at least 4 years follow-up (n=178). Slope correlated significantly with systolic blood pressure (r=0.26 and 0.29) in both groups, diastolic blood pressure only in the 4-year group (r=0.22) and average albuminuria in both (r=0.31 and 0.24). By multiple regression analyses systolic blood pressure and average albuminuria remained with significant influence on slope. Progression was defined as an increase in the category (e. g. normoto microalbuminuria) as well as an increase of more than 20% in albumin excretion, and was seen in 46 patients with at least 4 years' follow-up. Progressors (patients demonstrating progression) had higher systolic blood pressure (165 mm Hg±20 vs 156±17) and poorer glycaemic control (HbA1C: 8.2%±1.5 vs 7.7±1.3) p〈0.05, as well as a higher level of albuminuria at baseline. The present study points to systolic blood pressure and general level of albuminuria as factors determining the rate of progression of albuminuria. However, only a modest fraction of the variation between subjects was explained by these variables.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399799
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  • 6
    Electronic Resource
    Electronic Resource
    Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus? (1994)
    Springer
    Diabetologia 37 (1994), S. 788-796 
    Details
    ISSN: 1432-0428
    Keywords: Key words Autonomic function, diabetes mellitus, 24-h heart rate variability, microalbuminuria, sudden cardiac death, vagal function, autonomic neuropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The appearance of microalbuminuria in diabetic patients predicts development of macroalbuminuria and coronary heart disease. Autonomic dysfunction in ischaemic heart disease is related to an increased incidence of arrhythmic deaths. To assess sympathovagal balance in relation to microalbuminuria we performed 24-h spectral analysis of RR interval oscillations in 37 insulin-dependent diabetic patients. Patients were divided according to urinary albumin excretion as normo-(〈20 µg/min) (n =12), micro-(〉20 and 〈200 µg/min) (n =14) and macro-albuminuria (〉200 µg/min) (n =11). None had symptoms or signs of ischaemic heart disease at clinical examination or during stress testing. Fourteen matched healthy subjects served as controls. Overall RR interval variability was calculated as the 24-h standard deviation. The square root of power of the low-frequency (0.04–0.15 Hz) and high-frequency (0.15–0.40 Hz) component were considered indices of the sympathovagal interaction and vagal function, respectively. Patients with micro and macroalbuminuria had, compared to control subjects, significantly reduced 24-h standard deviation, a much smaller day/night difference in mean RR level and a significantly reduced amplitude of the low frequency and high frequency oscillations, which were even more reduced in macroalbuminuria. The differences in vagal function were also present after correction for mean RR level, and differences in physical training level and smoking. Insulin-dependent diabetic patients who develop microalbuminuria have significantly impaired vagal function and abnormal sympathovagal interaction, which is further deranged in macroalbuminuria. This early autonomic dysfunction may later contribute to a increased risk for sudden cardiac death. [Diabetologia (1994) 37: 788–796]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404336
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  • 7
    Electronic Resource
    Electronic Resource
    Systolic blood pressure relates to the rate of progression of albuminuria in NIDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 1251-1258 
    Details
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; albuminuria ; blood pressure ; rate of progression ; progressors ; glycaemic control.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We prospectively followed a cohort of 278 non-insulin-dependent (NIDDM) patients for a 6-year period, intending to estimate the rate of increase of albuminuria and to identify clinical variables that influence this increase. At baseline, normoalbuminuria (N) was seen in 74 %, microalbuminuria (M) in 19 % and 7 % presented with proteinuria (P). A total of 80 patients died; they were older (p 〈 0.001) and had higher albumin excretion both at baseline and as an average during follow-up (p 〈 0.01). At baseline, patients with proteinuria had higher blood pressures (systolic and diastolic), whereas there was no difference between patients with normo- and microalbuminuria. Glycaemic control was increasingly poor throughout the three groups. At follow-up, an average relative rate of increase of albuminuria (slope) of 17 % per year was seen both for patients with complete 6 years, follow-up (n = 135) and patients with at least 4 years follow-up (n = 178). Slope correlated significantly with systolic blood pressure (r = 0.26 and 0.29) in both groups, diastolic blood pressure only in the 4-year group (r = 0.22) and average albuminuria in both (r = 0.31 and 0.24). By multiple regression analyses systolic blood pressure and average albuminuria remained with significant influence on slope. Progression was defined as an increase in the category (e. g. normo- to microalbuminuria) as well as an increase of more than 20 % in albumin excretion, and was seen in 46 patients with at least 4 years' follow-up. Progressors (patients demonstrating progression) had higher systolic blood pressure (165 mm Hg ± 20 vs 156 ± 17) and poorer glycaemic control (HbA1C: 8.2 % ± 1.5 vs 7.7 ± 1.3) p 〈 0.05, as well as a higher level of albuminuria at baseline. The present study points to systolic blood pressure and general level of albuminuria as factors determining the rate of progression of albuminuria. However, only a modest fraction of the variation between subjects was explained by these variables. [Diabetologia (1994) 37: 1251–1258]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399799
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  • 8
    Electronic Resource
    Electronic Resource
    Early recognition of autonomic dysfunction in microalbuminuria: significance for cardiovascular mortality in diabetes mellitus? (1994)
    Springer
    Diabetologia 37 (1994), S. 788-796 
    Details
    ISSN: 1432-0428
    Keywords: Autonomic function ; diabetes mellitus ; 24-h heart rate variability ; microalbuminuria ; sudden cardiac death ; vagal function ; autonomic neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The appearance of microalbuminuria in diabetic patients predicts development of macroalbuminuria and coronary heart disease. Autonomic dysfunction in ischaemic heart disease is related to an increased incidence of arrhythmic deaths. To assess sympathovagal balance in relation to microalbuminuria we performed 24-h spectral analysis of RR interval oscillations in 37 insulin-dependent diabetic patients. Patients were divided according to urinary albumin excretion as normo-(〈20 Μg/min) (n=12), micro-(〉20 and 〈200 Μg/min) (n=14) and macro-albuminuria (〉200 Μg/min) (n=11). None had symptoms or signs of ischaemic heart disease at clinical examination or during stress testing. Fourteen matched healthy subjects served as controls. Overall RR interval variability was calculated as the 24-h standard deviation. The square root of power of the low-frequency (0.04–0.15 Hz) and high-frequency (0.15–0.40 Hz) component were considered indices of the sympathovagal interaction and vagal function, respectively. Patients with micro and macroalbuminuria had, compared to control subjects, significantly reduced 24-h standard deviation, a much smaller day/night difference in mean RR level and a significantly reduced amplitude of the low frequency and high frequency oscillations, which were even more reduced in macroalbuminuria. The differences in vagal function were also present after correction for mean RR level, and differences in physical training level and smoking. Insulin-dependent diabetic patients who develop microalbuminuria have significantly impaired vagal function and abnormal sympathovagal interaction, which is further deranged in macroalbuminuria. This early autonomic dysfunction may later contribute to a increased risk for sudden cardiac death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404336
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  • 9
    Electronic Resource
    Electronic Resource
    Acute renal effects of angiotensin converting enzyme inhibition in microalbuminuric type 1 diabetic patients (1993)
    Springer
    Acta diabetologica 30 (1993), S. 149-153 
    Details
    ISSN: 1432-5233
    Keywords: Angiotensin converting enzyme inhibition ; Microalbuminuria ; Renal haemodynamics ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The renal effects of intravenous injection of 40 mg enalapril were investigated in 16 normotensive microalbuminuric type 1 (insulin-dependent) diabetic patients. After enalapril the following changes were observed: fractional albumin clearance (Θ Alb) decreased from 9.9 (3.0–23.8) to 8.2 (2.0–18.3)×10−6 (2P〈0.01); filtration fraction (FF) decreased from 0.260 (0.225–0.312) to 0.253 (0.190–0.297) (2P〈0.01); renal plasma flow (RPF) increased from 565 (411–690) to 623 (449–785) (2P〈0.01); and glomerular filtration rate (GFR) remained stable at 149 (128–181) versus 150 (124–185) ml · min−1 (NS). These values were unchanged after placebo (n=8), except for RFP which decreased from 606 (401–701) to 559 (381–677) ml · min−1 (2P〈0.05) and GFR which was reduced from 148 (111–173) to 138 (111–167) (2P〈0.05). A reduction in mean blood pressure from 94 (87–103) to 89 (79–101) mmHg (2P〈0.05) was found in the enalapril group and a minor reduction in the placebo group from 97 (83–106) to 96 (81–104) mmHg (2P〈0.05) was also noted. The relative changes in systolic blood pressure in the enalapril group correlated with changes in Θ Alb (Spearman'sr=0.66, 2P〈0.02) and FF (r=0.53, 2P〈0.05). Acute inhibition of angiotensin converting enzyme does not reduce the pathological hyperfiltration in these patients and a reduction in Θ Alb and FF can not be dissociated from the reduction in blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00572859
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  • 10
    Electronic Resource
    Electronic Resource
    Reduced glomerular filtration rate and cardiovascular damage in diabetes: a key role for abnormal albuminuria (1992)
    Springer
    Acta diabetologica 29 (1992), S. 201-213 
    Details
    ISSN: 1432-5233
    Keywords: Abnormal albuminuria ; ACE-inhibition ; Hypertension ; Microalbuminuria ; Diabetic nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is general agreement that a fall rate in glomerular filtration rate (GFR) is the principal endpoint in diabetics with renal disease, and that abnormal albuminuria (including microalbuminuria) is an important intermediate end-point. The relative roles of blood pressure (BP) elevation and abnormal albuminuria in the prediction and genesis of renal disease are a matter of debate, and are further analysed in this paper. New studies show that neither genetic predisposition to hypertension (parental BP) nor parental abnormal albuminuria can be used to predict renal disease in patients with type 1 (insulin-dependent) diabetes. However, parental predisposition to proteinuria seems to be important to certain types of patients with type 2 (non-insulin-dependent) diabetes. Cross-sectional as well as follow-up studies document that GFR is generally well preserved in microalbuminuria (in both type 1 and type 2 patients), while the transition to clinical proteinuria is associated with a decline in GFR. Thus, prevention of overt proteinuria is important in clinical trials in microalbuminuric patients. In type 1 diabetes clear ultrastructural changes have been documented with microalbuminuria and a good correlation between abnormal albuminuria and structural damage is seen. Structural damage in normo- and microalbuminuric patients correlates poorly with BP. New studies in type 1 diabetes document that microalbuminuria (but not elevated BP) predicts not only clinical diabetic nephropathy but also end-stage renal failure and mortality. In type 2 diabetes microalbuminuria is the strongest predictor of mortality, whereas BP elevation is not a predictor. Several studies now document that antihypertensive treatment, especially with inhibitors of angiotensin converting enzyme, is able to reverse or reduce abnormal albuminuria, even in non-hypertensive type 1 patients, and possibly preserve GFR. Therefore, microalbuminuria may be the main indicator for starting antihypertensive treatment in these patients. With respect to organ damage in the retina, abnormal albuminuria is an important indicator of the risk of severe diabetic retinopathy. BP elevation seems not to be an initiating factor, but rather aggravates established retinopathy. Left ventricular hypertrophy has a stronger correlation with BP elevation than normoalbuminuria, suggesting that left ventricular hypertrophy is at least partially a phenomenon secondary to elevated BP in diabetic patients with abnormal albuminuria. Generally, abnormal albuminuria is a strong indicator of cardiovascular renal damage in diabetic patients and in most organs is a stronger factor than elevated BP.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00573489
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