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Biomedical subjects

T Deckert

Publications and source records attributed to T Deckert.

At least 37 records · Page 2Linked to original sources
PubMed1994

Endothelial function and serum lipids in the course of developing microalbuminuria in insulin-dependent diabetes mellitus.

Changed endothelial function and dyslipidemia are features of insulin-dependent diabetes mellitus complicated with clinical nephropathy. The time relationship between the appearance of these abnormalities is however not well known. We have therefore studied the coincidence of microalbuminuria, endothelial dysfunction and dyslipidemia during a 10 year prospective study of 209 insulin-dependent diabetic patients with normal urinary albumin excretion. Twenty-three patients developed progressing microalbuminuria defined as a median urinary albumin excretion > 30 mg/24-h in two consecutive years and a progression rate in albuminuria higher than 5% per year. Thirty patients who remained normoalbuminuric throughout the observation period were randomly selected to obtain a control group with comparable degree of glycaemic control. The mean level of von Willebrand factor before onset of microalbuminuria tended to be higher in patients developing microalbuminuria than in the control group (NS), but there was no increase in von Willebrand factor in the patients who developed microalbuminuria. Total cholesterol did not change, but a significant decrease in high density lipoprotein cholesterol was observed in patients who developed microalbuminuria. In conclusion, the study demonstrated coincidence of microalbuminuria and decreasing high density lipoprotein cholesterol, but no coincidence between onset of microalbuminuria and endothelial dysfunction assessed by von Willebrand factor.

Adolescent↗
PubMed1993

[Microalbuminuria--a valuable diagnostic parameter].

The concept of microalbuminuria is reviewed. Measuring the urinary albumin excretion rate and testing for microalbuminuria is well established in the control and treatment of patients with insulin-dependent diabetes mellitus. Microalbuminuria predicts nephropathy and early cardiovascular death. In the presence of microalbuminuria, frequent examinations are warranted for early detection of retinopathy, hypertension and for optimizing the glycaemic control. In patients with non-insulin dependent diabetes, the independent value of microalbuminuria as a cardiovascular risk factor is not yet clarified. The urinary albumin excretion rate should be measured at diagnosis, because the indications are that presence of microalbuminuria reinforces the urge to intervene against other well-documented cardiovascular risk-factors (hypertension, dyslipidemia, tobacco and obesity). In the non-diabetic population there is accumulating evidence that an elevated urinary albumin excretion rate is associated with early cardiovascular morbidity and mortality. Large scale cross-sectional and prospective studies are needed in order to further clarify the role of microalbuminuria as an independent risk factor in the background population.

Albuminuria↗
PubMed1993

Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria.

Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30-100 mg/24 h in group D2; 101-300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 mumol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of beta 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 A fractions in the range 26-64 A) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p < 0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 A dextran (p < 0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy.

Adult↗
PubMed1993

Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats.

Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6-10 mmol/l or 10-20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10-15% following short- and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p = 0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p = 0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r = -0.60, p < 0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.

Albuminuria↗
PubMed1993

Plasma disappearance of glycated and non-glycated albumin in type 1 (insulin-dependent) diabetes mellitus: evidence for charge dependent alterations of the plasma to lymph pathway.

The fractional plasma escape rates of glycated and non-glycated albumin have earlier been measured in groups of Type 1 (insulin-dependent) diabetic patients and control subjects. The escape of non-glycated albumin was similar in control subjects and normoalbuminuric patients, but elevated in patients with micro or macroalbuminuria. In all groups the escape rate of glycated albumin was lower than that of non-glycated albumin. Glycation increases the anionic charge of albumin. To assay for charge-dependent alterations of transport a selectivity index (non-glycated albumin/glycated albumin transport ratio) was determined from the disappearance data. The index was high in control subjects (1.021 +/- 0.0057 (SEM)). This reflects a mean difference between the two escape rates of 2.1% per hour (for comparison the mean of the fractional escape rate of non-glycated albumin of the normal control subjects was 4.7% per hour). The index was numerically even higher in normoalbuminuric patients (1.031 +/- 0.0047 (SEM)), but reached significantly lower levels in patients with microalbuminuria (1.013 +/- 0.0030 (SEM), p < 0.02). Patients with clinical nephropathy had very low levels indicating loss of selectivity (1.002 +/- 0.0068 (SEM), p < 0.001). This pattern accords well with measurements of renal clearance selectivity indices, suggesting a general, progressive deterioration of anionic perivascular barrier components in diabetic microangiopathy. The structural target for these changes is likely to be the glycosaminoglycans of the glomerular basal membrane and the interstitial matrix.

Albuminuria↗
PubMed1993

Glucosaminyl N-deacetylase in cultured fibroblasts; comparison of patients with and without diabetic nephropathy, and identification of a possible mechanism for diabetes-induced N-deacetylase inhibition.

Impaired heparan sulphate biosynthesis through diabetes-induced inhibition of glucosaminyl N-deacetylase may have a central role in the development of diabetic nephropathy, and genetic differences in the vulnerability of the N-deacetylase could influence the risk of developing nephropathy. We studied N-deacetylase activity in fibroblast cultures from Type 1 (insulin-dependent) diabetic patients with (n = 14) or without (n = 13) diabetic nephropathy, together with non-diabetic control subjects (n = 7). No difference in N-deacetylase activity was found (p = 0.13), and no inhibition of N-deacetylase was found in cultures grown at 25 mmol/l glucose. N-deacetylase activity was inversely correlated to growth rate (r = -0.59, p = 0.0008), and in patients with nephropathy a negative correlation between HbA1C and fibroblast N-deacetylase activity (r = -0.72, p = 0.012) was found. Cell-cycle analysis revealed an increased fraction of S-phase cells in patients with nephropathy (28%(21-52%)) compared to healthy control subjects (17% (9-24%)), p = 0.0008, but not between patients with and without nephropathy (latter group 26%(11-43%)), p = 0.43. Forskolin, an activator of protein kinase A, specifically decreased N-deacetylase activity, whereas activation of protein kinase C produced a combined reduction in N-deacetylase activity and total protein synthesis. In conclusion, no constitutive defects in N-deacetylase activity were found in fibroblasts from these patients. Further studies should consider possible associations between fibroblast characteristics and pre-biopsy environmental parameters related to cellular memory phenomena. Finally, activation of protein kinase A provides a potential general pathway for regulating N-deacetylase activity.

Adult↗
PubMed1992

Urinary excretion of retinol-binding protein in type 1 (insulin-dependent) diabetic patients with microalbuminuria and clinical diabetic nephropathy.

The urinary excretion of retinol-binding protein (RBP) was studied in 101 insulin-dependent diabetic patients allocated to three groups according to 24-h urinary albumin excretion rate (UAE) (median of three urine collections): group 1 (n = 45), normal UAE less than 30 mg/24 h; group 2 (n = 27), microalbuminuria (UAE 30-300 mg/24 h); and group 3 (n = 29), clinical diabetic nephropathy (UAE greater than 300 mg/24 h). We used 23 healthy subjects as controls. Fractional clearance of RBP (FC-RBP) and its 24-h urinary excretion rate (URBP) were higher in each diabetic group than in healthy subjects, the highest values being found in group 3. Groups 1 and 2 did not differ in URBP and FC-RBP. There was a correlation between FC-RBP and haemoglobin A1c in both the total diabetic cohort (P less than 0.001) and in diabetic patients in groups 1 and 2 with a glomerular filtration rate of more than 90 ml/min (P less than 0.05). No correlation was found between FC-RBP and UAE and/or duration of diabetes in any of the diabetic groups. We conclude that the increased urinary excretion of RBP, indicating proximal tubular dysfunction, is already present in normoalbuminuric insulin-dependent diabetic patients and correlates with metabolic control. Further deterioration in proximal tubular function was not observed in microalbuminuric patients, but is a late event in clinical diabetic nephropathy.

Adult↗
PubMed1992

Is diabetic nephropathy an inherited complication?

For yet unidentified reasons less than 50% of patients with insulin-dependent mellitus develop diabetic nephropathy. Genetic factors have been suggested as risk markers for development of nephropathy in diabetes. To further evaluate this hypothesis we studied the prevalence of nephropathy in diabetic siblings of diabetic patients with and without nephropathy. From a representative sample of 619 patients with insulin-dependent diabetes, we identified 20 patients with and 29 patients without nephropathy having diabetic siblings. Diabetic nephropathy (defined as urinary albumin excretion greater than 300 mg/24 hr) was found in 7 out of 21 siblings to patients with nephropathy and 3 out of 30 siblings to normoalbuminuric patients (P less than 0.04). No significant differences between the two groups of siblings with respect to age, diabetes duration, sex distribution, blood pressure or glycosylated hemoglobin A1c-levels were found. A significant correlation within sib-pair of glycosylated hemoglobin A1c was found (r = 0.47; P less than 0.001). We conclude that familial clustering of diabetic nephropathy does occur. This clustering may either be due to genetic inheritance or to sib-similarities due to shared environment, as indicated by the correlation of glycosylated hemoglobin A1c within sib-pairs.

Albuminuria↗
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

Transcapillary filtration of plasma protein in long-term type 1 (insulin dependent) diabetic patients.

To study the pathophysiologic mechanism leading to increased transcapillar sieving of albumin in patients with diabetic nephropathy, subcutaneous interstitial concentrations of albumin, transferrin, total IgG and IgG-4 was measured in 30 long-term type 1 diabetic patients using the skin suction blister method. Eight normal subjects served as controls. The patients were divided in groups according to their urinary albumin excretion: normal (n = 11), micro-albuminuria (n = 9), and clinical nephropathy (n = 10). Results were expressed as the blister to serum concentration ratio (Cb:Cs) of each macromolecule. Normoalbuminuric patients had lower Cb:CsIgG ratio than healthy controls (0.28 +/- 0.04 vs. 0.35 +/- 0.09, p = 0.03). The lowest Cb:CsIgG ratio (0.23 +/- 0.07) was found in patients with clinical nephropathy. The same trend could be demonstrated in the other Cb:Cs ratios, but differences there were not significant. No differences related to capillary charge- or size-selectivity could be demonstrated between the groups. The results might reflect an increase of intracapillary hydrostatic pressure or increased capillary hydraulic permeability in the diabetic state per se, augmented during the development of microvascular complications.

Adult↗
PubMed1992

Diabetic retinopathy, nephropathy and neuropathy. Generalized vascular damage in insulin-dependent diabetic patients.

The most serious complication of diabetes mellitus is clinical nephropathy. The development of persistent proteinuria (urinary excretion of more than 300 mg albumin/24 hours) implies an extremely high risk of early death. Renal failure is the most frequent cause of death but the mortality of cardiovascular diseases is also increased. Besides the link between albuminuria (nephropathy) and atherosclerosis in coronary arteries, albuminuria is also a predictor of microangiopathy in other organs than the kidneys. The annual incidence of proliferative retinopathy in early nephropathy is 10-15% compared to only 1% in patients without nephropathy. Also signs of cardiomyopathy have been demonstrated in early nephropathy. Further we have described markers of universal endothelial damage in these patients, and we hypothesize that albuminuria not only is a predictor of renal disease but also of widespread vascular disease. Long-term improvement of metabolic control by use of insulin infusion pumps and early antihypertensive treatment seem to stop the further progression of early diabetic nephropathy and to significantly improve the prognosis of clinical nephropathy.

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

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

Possible genetic defects in regulation of glycosaminoglycans in patients with diabetic nephropathy.

The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of [2H] glucosamine and [35S] sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of [3H] glucosamine into HA, CS + DS, and HS and [35S] sulfate into CS + DS and HS were not significantly different between the three groups. However, the fractional incorporation of [3H]glucosamine into HS was significantly reduced in diabetic patients with nephropathy compared with control subjects. This was the case not only when related to the total amount of GAGs (P = 0.014) but also when related to HA (P = 0.014). No significant difference was seen between control subjects and normoalbuminuric diabetic patients. The degree of N-sulfation of HS was not significantly different between the experimental groups. The results suggest that patients with diabetic nephropathy may suffer from deficiencies of coordinate regulation in the biosynthesis of GAG in fibroblasts, which may lead to a reduced density of HS in the extracellular matrix. If these changes reflect alterations in the biosynthesis of GAG from endothelial, myomedial, and mesangial cells, this observation may be relevant for the pathogenesis of severe diabetic complications.

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↗