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  • 1
    ISSN: 1432-0428
    Keywords: Autoregulation ; diabetic microangiopathy ; subcutaneous blood flow ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Autoregulation of blood flow in subcutaneous tissue was studied at the level of the lateral malleolus in eight long-term Type 1 (insulin-dependent) diabetic patients with clinical microangiopathy, eight short-term Type 1 diabetic patients without clinical microangiopathy and seven healthy control subjects. Blood flow was measured by the local 133Xenon washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevating to a maximum of 70 mmHg by head-up tilt; in the latter position venous pressure was kept constant and low by activation of the leg muscle vein pump (heel raising). Mean arterial blood pressure was thus varied between 60 and 160 mmHg. In normal and short-term diabetic subjects blood flow remained within 10% of control values during the changes in arterial blood pressure. In six of the eight Type 1 diabetic patients with clinical microangiopathy, autoregulation of blood flow was impaired, blood flow changing ap proximately 20% per 10 mmHg change in arterial blood pressure; the slope of the autoregulation curves was significantly higher compared with the two control groups (p〈0.02). Resting mean arterial blood pressure was significantly elevated in long-term diabetic patients (median: 107 mmHg) compared with short-term diabetic (median: 85 mmHg) and control subjects (median: 91 mmHg) (p〈0.01 and p〈0.02, respectively). No correlation was, however, demonstrated between resting mean arterial blood pressure and the degree of disturbed autoregulation, but a relationship was demonstrated between the degree of disturbed autoregulation and the amount of periodic acid Schiff positive material in the terminal arteriolar walls of the investigated area (p〈0.05).
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  • 2
    ISSN: 1432-0428
    Keywords: Diabetic nephropathy ; glomerular filtration rate ; hypertension ; proteinuria ; insulin-dependent diabetes ; serum creatinine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (〉 0.5 g/day) secondary to diabetic nephropathy. Twelve of the 14 patients had normal serum creatinine levels. None of the patients received antihypertensive treatment. During the mean observation period of 26 months (range 23 to 33 months) GFR decreased from 107 to 87 ml/min/1.73 m2 (p〈 0.001), serum creatinine remained unchanged: 107 and 112/gmmol/l (NS), proteinuria increased from 1.8 to 3.3 g/day (p〈0.001) and arterial blood pressure rose from 132/88 to 153/101 mmHg (p〈0.001). Glomerular filtration rate decreased linearly with time (slope=−0.75, r=0.99, p〈0.001) by a mean of 0.75 ml/min/month (range 0.1 to 1.5 ml/ min/month). The decrease in GFR did not correlate with sex, age at onset, duration of diabetes, arterial blood pressure, proteinuria, insulin requirement, postprandial blood glucose or the initial GFR, but numbers were small. The decline in GFR in each individual was constant, but varied considerably between patients. Increase in arterial blood pressure to a hypertensive level is an early feature of diabetic nephropathy in young insulin-dependent diabetics.
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  • 3
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 4
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes ; blood glucose concentration ; glomerular filtration rate ; renal plasma flow ; albumin, β-2-microglobulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of intravenous glucose infusion on glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) and on urinary excretion of albumin and β-2-microglobulin were studied in ten normal subjects and seven metabolically well-controlled insulin-dependent diabetics. Following glucose infusion in normal subjects (n = 10) blood glucose increased from 4.7±0.1 to 10.9±0.4 mmol/1 (SEM) (p ⩽ 0.01). Glomerular filtration rate increased from 116±2 to 123±3ml/min x 1.73 m2 (p ⩽ 0,01), while no change in renal plasma flow was seen 552±11 versus 553±18 ml/min × 1.73 m2. Volume expansion with intravenous saline infusion in six of the normal subjects induced no changes in blood glucose or kidney function. In seven strictly controlled insulin-dependent diabetics, blood glucose values were raised from 4.6±0.4 to 16.0±0.6 mmol/1 and clamped by means of an ‘artificial beta cell’. Glomerular filtration rate increased in all patients, from 133 ±5 to 140±6 ml/min × 1.73 m2 (p ⩽ 0.02), as did renal plasma flow from 576±26 to 623±38 ml/ min × 1.73 m2 (p ⩽ 0.02). Urinary albumin excretion remained unchanged in both normal subjects and diabetics. β-2-microglobulin excretion rate increased significantly in the diabetics following glucose infusion, while no significant change was seen in the normal subjects. Our results show that hyperglycaemia per se contributes to the increased glomerular filtration rate and renal plasma flow in insulin-dependent diabetes.
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  • 5
    ISSN: 1432-0428
    Keywords: Streptozotocin ; diabetes ; rat ; micropuncture ; renal plasma flow ; glomerular filtration ; hydraulic pressure ; ultrafiltration coefficient
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Renal function was examined with micropuncture methods in the insulin-treated streptozotocin-diabetic rat. Kidney glomerular filtration rate was significantly higher in the diabetic rats (1.21 ml/min) than in the control group (0.84 ml/min) Nephron glomerular filtration rate increased in proportion to the rise in kidney glomerular filtration rate (diabetic rats: 37.0 nl/min; control rats: 27.9 nl/min). Likewise renal plasma flow was significantly higher in the diabetic rats (4.1 ml/min) than in the control group (3.0 ml/min). Glomerular capillary pressure was identical in both groups (56.0 and 56.0 mmHg, respectively). The proximal intratubular pressure was significantly reduced in the diabetic rats (10.4 mmHg; control value: 12.5 mmHg). The effective glomerular ultrafiltration coefficient was slightly but not significantly higher in the diabetic rats (0.027 nl s-1mmHg-1) than in the control group (0.023 nl s-1mmHg-1). Kidney weight was significantly higher in the diabetic rats (1.15 g; control rats: 0.96 g) while body weight was similar in both groups (diabetic rats: 232 g; control rats: 238 g). Calculations indicate that the increases in transglomerular hydraulic pressure, renal plasma flow and ultrafiltration co-efficient of the glomerular membrane contribute about equally to the rise in glomerular filtration rate. The increases in the values of the determinants of glomerular filtration rate may be the result of renal hypertrophy. These studies suggest that this model provides a useful method for investigating kidney function in diabetes, which may have relevance for our understanding of the kidney abnormalities in human diabetes.
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  • 6
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; diabetic microangiopathy ; skeletal muscle ; blood flow measurement ; 133Xe washout ; maximal ischaemic exercise ; papaverine ; atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study was undertaken to determine whether the distensibility of a passive vascular bed is reduced in Type 1 (insulin-dependent) diabetic patients with microangiopathy. The change in blood flow induced by 45° head-up tilting was studied in two systems: (a) following maximal ischaemic exercise and (b) in a vascular bed locally paralysed by the injection of papaverine. Five normal subjects, six patients with long-standing Type 1 diabetes and six non-diabetic patients with severe atherosclerosis affecting the legs were studied. Blood flow was measured in the anterior tibial muscle by the isotope washout technique. The median increase in blood flow produced by tilting was greater in normal subjects than in diabetic subjects in both the locally-relaxed bed (58% and 14% respectively) and after maximal ischaemic exercise (45% and 4% respectivley). In the atherosclerotic subjects, the increase in blood flow in the locally relaxed bed was 77%. The results are consistent with the hypothesis that the reduced distensibility seen in the diabetic subjects was related to the presence of microvascular disease and that the behaviour of a vascular bed relaxed by the local injection of papaverine might be an appropriate model to study this condition.
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  • 7
    ISSN: 1432-0428
    Keywords: Autoregulation, blood flow ; 133Xe washout ; postural change ; diabetic microangiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Autoregulation of blood flow was studied in skeletal muscle and subcutaneous tissue in seven Type 1 (insulindependent) diabetic patients (median age: 36 years) with nephropathy and retinopathy and in eight normal subjects of the same age. Blood flow was measured by the local 133Xe washout technique. Reduction in arterial perfusion pressure was produced by elevating the limb 20 and 40 cm above heart level. Blood flow remained within 10% of control values when the limb was elevated in normal subjects. In five of the seven diabetic subjects blood flow fell significantly in both tissues when the limb was elevated 40 cm indicating impaired autoregulation. The results suggest that intrinsic vascular (arteriolar) mechanisms (myogenic and/or metabolic) underlying the normal autoregulatory response are defective in some diabetic patients with microangiopathy.
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  • 8
    ISSN: 1432-0428
    Keywords: Autoregulation ; arterial blood pressure ; glomerular filtration ; diabetic nephropathy ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of acute lowering of arterial blood pressure upon kidney function in nephropathy was studied in 13 patients with long-term Type 1 (insulin-dependent) diabetes. Ten normal subjects (six normotensive and four hypertensive) and five short-term Type 1 diabetic patients without nephropathy served as controls. Renal function was assessed by glomerular filtration rate (single bolus 51Cr-EDTA technique) and urinary albumin excretion rate (radial immunodiffusion). The study was performed twice within 2 weeks, with the subjects receiving an intravenous injection of either clonidine (225 μg) or saline (0.154 mmol/l). The arterial blood pressure was similar in the diabetic patients with nephropathy (mean 136±11 mmHg) and in the non-diabetic control subjects 88±5 (mean 140±25 mmHg). The clonidine injection induced sim- 92±15 ilar reductions in mean arterial blood pressure in all three groups (16–18 mmHg). While glomerular filtration rate and urinary albumin excretion rate remained unchanged in both control groups after clonidine injection, glomerular filtration rate dimished from 78 to 71 ml/min per 1.73 m2 (p〈0.01), and urinary albumin excretion declined from 1707 to 938 μg/min (p〈0.01) in the patients with diabetic nephropathy. Our results suggest that an intrinsic vascular (arteriolar) mechanism underlying the normal autoregulation of glomerular filtration rate, i. e. the relative constancy of glomerular filtration rate that occurs in response to rather wide variations in perfusion pressure, is defective in diabetic nephropathy.
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  • 9
    ISSN: 1432-0428
    Keywords: Autoregulation ; arterial blood pressure ; glomerular filtration ; incipient diabetic nephropathy ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus 51Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 μg) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79±13/8 to 104/68±9/7 mmHg (p 〈 0.01), urinary albumin excretion rate from 68 (31–369) to 46 (6–200) μg/min (median and range) (p〈0.01), and fractional clearance of albumin in all patients (median 29%) (p 〈 0.01). Glomerular filtration rate was 110±11 before and 106±13 ml/min/1.73 m2 after clonidine injection. The blood glucose concentration was 15±4mmol/l before and 14±5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.
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  • 10
    ISSN: 1432-0428
    Keywords: Microscopic haematuria ; persistent proteinuria ; diabetic glomerulosclerosis ; non-diabetic glomerulopathy ; Type 1 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The prevalence and causes of microscopic haematuria were examined in all Type 1 (insulin-dependent) diabetic patients with persistent proteinuria (diabetes duration ⩾5 years) attending the outpatient clinic at Hvidöre Hospital during 1985. One hundred eighty-four patients (69F/115M) out of 1024 Type 1 patients had persistent proteinuria (18%). Microscopic haematuria was defined as ⩾3 erythrocytes per high power field in two or more sterile urine samples. Twenty-three Type 1 patients with persistent proteinuria (7F/16M, aged 35.4±13 years) had microscopic haematuria (12.5%). No significant changes were found between the group with and without microscopic haematuria: blood pressure 148/89±22/11 versus 145/91±20/11 mmHg, duration of diabetes when persistent albuminuria occurred 17±8 versus 20±10 years, serum creatinine 99±24 versus 98±31 μmol/l, simplex retinopathy 61 versus 54%, proliferative retinopathy 39 versus 42%, and no signs of retinopathy 0 versus 4%. Kidney biopsy was performed in 13 out of the 23 patients with microscopic haematuria. Diabetic glomerulosclerosis was present in all 13 patients, but 9 patients had a non-diabetic renal disease superimposed (mesangioproliferative glomerulonephritis (n=5), membranous glomerulonephritis (n=3) and sarcoidosis (n=1). Microscopic haematuria is a rare finding, frequently reflecting superimposed non-diabetic glomerulopathies, in Type 1 diabetic patients with diabetic nephropathy and well preserved kidney function.
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