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Biomedical subjects

B Feldt-Rasmussen

Publications and source records attributed to B Feldt-Rasmussen.

At least 73 records · Page 4Linked to original sources
PubMed1993

A comparison of spirapril and isradipine in patients with diabetic nephropathy and hypertension.

The effects of spirapril and isradipine on blood pressure, urinary albumin excretion and sodium-volume homeostasis in hypertensive insulin-dependent diabetic patients with nephropathy were assessed. Fifteen Type 1 diabetic patients aged 28-53 years with a diabetes duration of 19-37 years were studied. All had hypertension and diabetic nephropathy with a urinary albumin excretion of more than 300 mg/24 h. After a single blind placebo treatment period of 4 weeks the patients were randomly assigned to treatment with the calcium antagonist isradipine SRO 5 mg once daily or the ACE inhibitor spirapril 6 mg once daily for 6 months in a double-blind design. Isradipine lowered ambulatory systolic blood pressure from 152 +/- 12 to 141 +/- 11 mmHg (p < 0.05) and ambulatory diastolic pressure from 91 +/- 9 to 86 +/- 8 mmHg (p < 0.05). The blood pressure lowering effect of spirapril was similar: 156 +/- 13 vs 143 +/- 11 mmHg (p < 0.01) and 90 +/- 4 vs 84 +/- 4 mmHg (p < 0.05). The fractional albumin clearance was unchanged on isradipine but decreased after 6 months treatment with spirapril with on average 20% (p < 0.05). Total body exchangeable sodium decreased on spirapril treatment: 2994 +/- 296 vs 2636 +/- 194 meq/1.73 m2 (p < 0.05) and extracellular volume tended to do so (p = 0.12). On isradipine treatment these parameters remained unchanged. In conclusion both isradipine and spirapril lowered blood pressure in patients with diabetic nephropathy. Only the ACE inhibitor had demonstrable beneficial effects on urinary albumin excretion rate and the sodium-volume expansion seen in these patients.

Adult↗
PubMed1992

Microalbuminuria. Implications for micro- and macrovascular disease.

Microalbuminuria is diagnosed when the UAER is greater than 20 but less than 200 micrograms/min. The prevalence of microalbuminuria among diabetic patients is 15-20%. Persistent microalbuminuria in diabetic patients is a risk marker not only of renal disease, but also of proliferative retinopathy and cardiovascular morbidity and mortality. Even among nondiabetic individuals, those with microalbuminuria tend to have an increased cardiovascular morbidity. The established cardiovascular risk factors, such as smoking, elevated plasma cholesterol, fibrinogen, and hypertension, are seen more frequently in diabetic patients with persistent microalbuminuria than in normoalbuminuric diabetic patients of similar age, sex, and diabetes duration. However, these risk factors cannot by themselves explain the cardiovascular overmortality in these patients. In addition, insulin resistance or genetic disposition to hypertension or cardiovascular disease fails to be the missing link. Accumulating evidence suggests a common pathogenetic mechanism for microalbuminuria and premature atherosclerosis (i.e., qualitative alterations of the extracellular matrix, including decreased density and sulfation of HS-PG). Decreased density of HS in the glomeruli may lead to albuminuria and mesangial proliferation. In the intima of large vessel walls, decreased density and/or sulfation of HS may enhance several of the processes involved in premature atherosclerosis. Diabetes affects the composition and structure of the extracellular matrix in many ways and leads to decreased density and sulfation of HS-PG by several mechanisms. Genetic differences in the sulfation of HS and/or genetic defects in the coordinated biosynthesis of HS-PG might contribute to decreased concentration and sulfation of HS-PG in susceptible individuals. It is hoped that susceptibility genes can be identified soon, thereby making prevention of severe late diabetic complications more successful.

Albuminuria↗
PubMed1992

Effects of isradipine in Type 1 (insulin-dependent) diabetic patients with albuminuria and normal blood pressure.

The effects of the calcium channel blocker, isradipine, on BP, urinary albumin excretion, plasma lipoproteins and natriuresis in albuminuric Type 1 (insulin-dependent) diabetic patients were assessed. Fifteen Type 1 diabetic patients aged 22-52 years were studied. All had elevated urinary albumin excretion (more than 30 mg/24h) based on several 24 h urine collections, and BP was normal (below 140/90 mmHg). After a placebo treatment period of eight weeks the patients were randomly assigned to two groups for a double-blind crossover study. Each patient received either 2.5 mg isradipine twice daily or placebo for eight weeks. Then, after 4 weeks (the wash-out period), each patient received the drug he or she had not taken before for another 8 weeks. Systolic blood pressure was lowered by 8 mmHg from 127 (114-139) mmHg (P less than 0.01) and diastolic by 5 mmHg from 81 (70-87) mmHg (P less than 0.03) during isradipine treatment. The 24 h urinary sodium excretion increased and no signs of volume expansion were observed during treatment with isradipine. Urinary albumin excretion and total body exchangeable sodium remained unchanged. During isradipine treatment the plasma concentrations of VLDL cholesterol and triglyceride decreased significantly (P less than 0.01) and the level of HDL cholesterol increased, but not significantly (P = 0.08). In conclusion, treatment of Type 1 diabetic patients, at risk of progressive clinical nephropathy, with the calcium channel blocker, isradipine, had beneficial effects on plasma lipoprotein levels and resulted in a reduction in BP. We did not find any effect of isradipine on urinary albumin excretion.

Albuminuria↗
PubMed1991

Effect of improved metabolic control on loss of kidney function in type 1 (insulin-dependent) diabetic patients: an update of the Steno studies.

We re-examined 69 of the 70 patients entering the two independent Steno Studies of effects of improved metabolic control on progression of late diabetic complications. They were analysed according to an intent to treat after follow-up for 8 years (Steno Study 1) and 5 years (Steno Study 2). The glycaemic control had improved in the insulin infusion group compared with the conventional treatment group (mean HbA1c) by 2.0 +/- 0.6% vs 0.7 +/- 1.2 in Steno Study 1 and by 1.8 +/- 1.2% vs 0.4 +/- 1.3 (p less than 0.01) in Steno Study 2. In the insulin infusion groups three patients had died during episodes of ketoacidosis. These were not caused by malfunction of the insulin infusion pumps. In the conventional treatment groups, three patients suffered five cardiovascular events causing two deaths. From the sixth month of Steno Study 1 the annual change of the glomerular filtration rate was -3.7 (-5.4 to -2.0) ml.min-1.1.73 m-2 vs -1.0 (-2.1 to -0.1) (conventional vs insulin infusion group, mean (95% confidence interval, p less than 0.01]. The change in urinary albumin excretion was associated with the glycaemic control (n = 69, r = 0.49, p less than 0.0002). No progression was observed among 32 patients with low range microalbuminuria (30 to 99 mg/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effects of insulin on renal haemodynamics and sodium handling in normal subjects.

Diabetic patients treated with insulin injected subcutaneously are characterized by peripheral hyperinsulinaemia and an increased mass of total body exchangeable sodium. We hypothesized that this may cause, at least in part, the glomerular hyperfiltration seen in the diabetic state. Six normal subjects were studied on 2 days in random order. Day A: Basal state for 40 min, hyperinsulinaemic euglycaemic clamp for 1 h (insulin infusion rate 2 mU kg-1 min-1 and 50% glucose infusion) and hyperinsulinaemic euglycaemic clamp combined with volume expansion (2 1 isotonic sodium chloride) for 2 h. Day B: as day A, but without insulin and glucose infusion. During combined volume expansion and hyperinsulinaemia an increase in glomerular filtration rate (GFR) (128 +/- 6 vs 117 +/- 8 ml min-1 1.73 m-2, p less than 0.01) and lithium clearance (CLi) (50 +/- 4 vs 33 +/- 5 ml min-1 1.73 m-2, p less than 0.01) was observed compared with basal conditions. GFR and CLi were unchanged during day B. Insulin infusion reduced renal sodium excretion. Absolute proximal tubular reabsorption was unchanged on both days. Insulin infusion without volume expansion caused a decrease of 24% in the fractional distal sodium excretion. Superimposed volume expansion and the concomitant increase in GFR and CLi was accompanied by a subsequent enhanced fractional distal sodium excretion of 27%. The changes in plasma concentrations of aldosterone, renin, angiotensin II, atrial natriuretic peptide and catecholamines did not explain the differences in GFR. An increase in GFR of 10%, comparable with that observed in diabetic patients, was induced by combined hyperinsulinaemia and volume expansion in euglycaemic normal subjects. The enhanced GFR is probably a compensatory response to the sodium retention induced by the action of insulin on the distal tubules.

Adult↗
PubMed1991

Is hypertension a major independent risk factor for retinopathy in type 1 diabetes?

Hypertension is an established risk factor for retinopathy. Whether it is an independent risk factor or acts only by association with nephropathy is not known. Therefore, we studied 273 Type 1 diabetic patients. They were divided into four groups. Group 1 (n = 55) were normotensive and normoalbuminuric, group 2 (n = 51) had hypertension but were normoalbuminuric, group 3 (n = 33) had nephropathy but were normotensive, and group 4 (n = 134) had nephropathy and hypertension. Hypertensive patients with normoalbuminuria (blood pressure 146 +/- 19 (+/-SD)/87 +/- 12 mmHg) had the same prevalence of retinopathy as normoalbuminuric normotensive patients (123 +/- 12/75 +/- 5 mmHg). Hypertensive nephropathic patients (blood pressure 147 +/- 18/87 +/- 8 mmHg) had more retinopathy than hypertensive normoalbuminuric patients despite similar blood pressure (normal retina/advanced retinopathy: 3%/73% vs 46%/17%, p less than 0.001). Nephropathic normotensive patients had worse retinal changes than hypertensive normoalbuminuric patients (19%/49%, p less than 0.001) but fewer than the nephropathic hypertensive patients p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Natural history of diabetic complications: early detection and progression.

Until recently Type 1 diabetes has been characterized by a considerable degree of mortality, mainly associated with the development of diabetic nephropathy. Diabetic nephropathy is characterized by persistent proteinuria, decreasing glomerular filtration rate (GFR), increasing blood pressure, and morphological changes. Proteinuria represents a late stage in a prolonged process, which begins at the onset of Type 1 diabetes, when urinary albumin excretion is at the lower end of its normal range (less than 10 mg 24-h-1). However, in those patients who will later develop persistent proteinuria, urinary albumin excretion increases exponentially at about 20% per year. These patients also tend to have rising blood pressure and falling GFR, higher rates of proliferative retinopathy and coronary heart disease, and elevated levels of cardiovascular risk factors. As intervention is possible in all these areas, identification of such patients is required and especially as the imposition of strict metabolic control may postpone or arrest progression to overt nephropathy. Where patients deteriorate despite such control the institution of early antihypertensive therapy and the effective management of end stage renal disease will bring further improvements in the prognosis of diabetic nephropathy.

Adult↗
PubMed1991

Impaired left-ventricular function in insulin-dependent diabetic patients with increased urinary albumin excretion.

Cardiac function was studied in 30 patients with insulin-dependent diabetes mellitus. Three groups, matched for age and diabetes duration, were defined as: group I (n = 10), normal urinary albumin excretion less than 30 mg 24 h-1; group II (n = 10), incipient diabetic nephropathy (urinary albumin excretion in the range of 30-300 mg 24 h-1); and group III (n = 10), clinical diabetic nephropathy (urinary albumin excretion greater than 300 mg 24 h-1). Ten non-diabetic subjects matched for sex and age served as controls. The left-ventricular end-diastolic volume measured by radionuclide cardiography was, at rest and during exercise, lower in group II and III compared with controls (p less than 0.05), while intermediate values were found in group I. The cardiac output was similar in the control group and group I; it was reduced, but not significantly so (p = 0.10), in group III and was significantly lower in group II (p less than 0.05). Stroke volume was also lower in group II and III than in controls (p less than 0.05), but not so in group I. These differences could not be explained by differences in metabolic control, blood pressure, blood volume status, degree of autonomic neuropathy or frequency of coronary heart disease. Our results might suggest that insulin-dependent diabetic patients with slightly but persistently elevated urinary albumin excretion have reduced diastolic compliance of the left-ventricle leading to impaired cardiac performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion: effect of long-term improved metabolic control.

Forty-seven patients with type 1 (insulin-dependent) diabetes mellitus and 14 normal subjects had renal volume determined by an ultrasonic technique. Renal volume of 299 +/- 49 ml/1.73 m2 (mean +/- SD) in type 1 diabetic patients with normal urinary albumin excretion exceeded that in the normal subjects (245 +/- 53 ml/1.73 m2, p less than 0.05). Compared with diabetic patients with normal urinary albumin excretion, renal volume was significantly higher in patients with microalbuminuria (372 +/- 24 ml/1.73 m2, p less than 0.05) and patients with clinical nephropathy (352 +/- 48 ml/1.73 m2, p less than 0.05). In a multiple linear regression with HbA1c, urinary albumin excretion, age, diabetes duration and mean blood pressure as independent variables, variations in HbA1c could account for 33% of the variations in kidney volume (n = 47, r = 0.57, p less than 0.01). The other variables played no role. When only patients without clinical nephropathy were included, HbA1c and kidney volume remained significantly correlated (n = 34, r = 0.60, p less than 0.01). In those patients a strong correlation between kidney volume and function, i.e. the glomerular filtration rate was found (n = 34, r = 0.70, p less than 0.01); metabolic control and function were also correlated (n = 34, r = 0.62, p less than 0.01). The urinary albumin excretion accounted for only 6% of the variation of the kidney volume (NS). In nine patients with microalbuminuria the kidney volume could be reduced during 2 years of improved metabolic control by means of insulin infusion pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Prevalence of hypertension in type 1 (insulin-dependent) diabetes mellitus.

The prevalence of hypertension in a representative sample (n = 10202) of the Danish general population aged 16-59 years was assessed to 4.4% based on three blood pressure readings. In Type 1 (insulin-dependent) diabetic patients of similar age (n = 1703) the prevalence was determined in a similar way to 14.7% (p less than 0.00001). The excess prevalence in Type 1 diabetic patients was due to hypertension in patients with incipient and clinical nephropathy as the prevalence of hypertension among diabetic patients with normal urinary albumin excretion (essential hypertension) was 3.9%, similar to that observed in the general population. The patients with Type 1 diabetes and essential hypertension had higher systolic (146 +/- 19 vs 133 +/- 18 mm Hg, p less than 0.00001) and diastolic blood pressure (87 +/- 12 vs 79 +/- 7 mm Hg, p less than 0.00001), but less changes in the eye background than patients with incipient nephropathy (urinary albumin excretion 30-300 mg/24 h) (p less than 0.03), indicating that the two groups were also different with respect to other microangiopathic lesions. Patients with essential hypertension were defined as having a normal urinary albumin excretion before and during antihypertensive treatment (if any). They were followed-up for a 58 (6-234) month period. We confirmed that hypertension is more common among Type 1 diabetic patients than in the general population and found the prevalence of essential hypertension similar in Type 1 diabetic patients to the non-diabetic population. This supports our hypothesis that hypertension is very unlikely to be the cause of diabetic nephropathy.

Adolescent↗
PubMed1990

Nephrotoxicity of cyclosporin A in patients with newly diagnosed type 1 diabetes mellitus.

Renal function was studied in 18 patients with Type 1 diabetes mellitus. All were participating in the Canadian-European randomized placebo-controlled cyclosporin trial in newly diagnosed Type 1 diabetic patients, nine being randomized to placebo, and nine to cyclosporin A. During treatment for 12 to 18 months, cyclosporin A caused significant reductions in the glomerular filtration rate (before drug withdrawal, cyclosporin 97 +/- 18 vs placebo 125 +/- 16 ml min-1 1.73-m-2, p less than 0.05), renal plasma flow (454 +/- 83 vs 536 +/- 70 ml min-1 1.73-m-2, p less than 0.05), and lithium clearance (17 +/- 3 vs 28 +/- 5 ml min-1 1.73-m-2, p less than 0.05). The fractional proximal reabsorption was increased (0.82 +/- 0.03 vs 0.78 +/- 0.03, p less than 0.05), and the fractional distal sodium reabsorption reduced (0.88 +/- 0.03 vs 0.94 +/- 0.02, p less than 0.05). These results are in accordance with the hypothesis that the nephrotoxic effect of cyclosporin A results from a preferential constriction of afferent glomerular vessels. One year after withdrawal of the drug, all variables were similar in the two groups, except for blood glucose control which was worse in the cyclosporin A treated group. When corrected for differences in blood glucose control it appeared that in three out of nine patients glomerular filtration rate had not completely returned to the reference range of the placebo group. We conclude that the nephrotoxic side-effects of cyclosporin A treatment for 1 year are reversible. There are, however, signs of minor and perhaps chronic renal injury.

Adult↗
PubMed1989

Features of endothelial dysfunction in early diabetic nephropathy.

The release of tissue plasminogen activator (tPA) by vascular endothelial cells during exercise was studied in forty men with insulin-dependent diabetes. Three groups, matched for age and diabetes duration, were defined as: group I (n = 19), normal urinary albumin excretion (less than 30 mg/24 h); group II (n = 11), incipient diabetic nephropathy (30-300 mg albumin excreted per 24 h); and group III (n = 10), clinical diabetic nephropathy (more than 300 mg albumin excreted per 24 h). Nine non-diabetic men served as controls. The rise in tPA antigen with exercise was similar in the controls and group I but significantly smaller in groups II and III (p less than 0.01). The albumin transcapillary escape rate was significantly higher in groups II and III than in group I and normal controls (p less than 0.01). The basal plasma level of von Willebrand factor was higher in groups III (p less than 0.01) and II (difference not significant, p = 0.06) than in group I and normal controls. These findings suggest that insulin-dependent diabetic patients with only slightly raised urinary albumin excretion have general endothelial cell dysfunction or damage. It is not yet clear whether these changes are important in the pathogenesis of thrombosis and atherosclerosis in these patients.

Adolescent↗
PubMed1989

Albuminuria reflects widespread vascular damage. The Steno hypothesis.

Albuminuria in Type 1 (insulin-dependent) diabetes is not only an indication of renal disease, but a new, independent risk-marker of proliferative retinopathy and macroangiopathy. The coincidence of generalised vascular dysfunction and albuminuria, advanced mesangial expansion, proliferative retinopathy, and severe macroangiopathy suggests a common cause of albuminuria and the severe renal and extrarenal complications associated with it. Enzymes involved in the metabolism of anionic components of the extracellular matrix (e.g. heparan sulphate proteoglycan) vulnerable to hyperglycaemia, seem to constitute the primary cause of albuminuria and the associated complications. Genetic polymorphism of such enzymes is possibly the main reason for variation in susceptibility.

Albuminuria↗
PubMed1989

Normal urinary albumin excretion in recently diagnosed type 1 diabetic patients.

The urinary excretion of albumin and retinol binding protein were measured in 51 recently diagnosed Type 1 diabetic patients and 48 control subjects, matched for age and sex. The diabetic patients, admitted consecutively to the Steno Memorial Hospital, were all studied 3 to 6 months after the onset of diabetes. Urinary albumin excretion (median and 95% confidence interval) was similar in the diabetic patients and normal control subjects (8 (6-11) vs 8 (6-11) mg 24-h-1, NS). Four diabetic patients had urinary albumin excretion in the microalbuminuric range of 30-300 mg 24-h-1. There was no significant difference between the two groups in urinary excretion of retinol binding protein. The distribution among the individuals of both urinary proteins was positively skewed and similar in the two groups. In conclusion, no significant differences in the urinary excretion of albumin and retinol binding protein were found between recently diagnosed Type 1 diabetic patients and normal subjects.

Adult↗
PubMed1989

The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients.

The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal tubular flow. This suggests that on-going cimetidine treatment must be taken into account when graft function is evaluated by the CCr alone.

Absorption↗