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Biomedical subjects

H H Parving

Publications and source records attributed to H H Parving.

At least 163 records · Page 9Linked to original sources
PubMed1993

Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

The effect of long-term, aggressive, antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin-dependent diabetic patients (mean age, 30 years). Renal function was assessed every 4 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and by albuminuria (radial immunodiffusion). During the median pretreatment period of 2.4 years (range, 1.9 to 5.5 years), the GFR decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 9.7-year (range, 2.8 to 10.4 year) period of antihypertensive treatment with metoprolol, hydralazine, and furosemide, the arterial blood pressure decreased from 143/96 mm Hg to 130/84 mm Hg and albuminuria decreased from 1,038 micrograms/min to 547 micrograms/min. The rate of decline in GFR decreased from 10.7 mL/min/yr (range, 5.3 to 17.5 mL/min/yr) before treatment to 2.5 mL/min/yr (range, 0.5 to 4.8 mL/min/yr) during treatment. The rate of decline in GFR is significantly smaller during the last 6 years compared with the first 3 years in patients who received long-term antihypertensive treatment (> or = 9 years). One patient died from acute myocardial infarction (GFR, 46 mL/min/1.73 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

Adult↗
PubMed1993

Impact of arterial blood pressure and albuminuria on the progression of diabetic nephropathy in IDDM patients.

To evaluate the impact of systemic blood pressure and albuminuria on the progression of diabetic nephropathy, we followed 41 IDDM patients with persistent albuminuria (> 300 mg/24 h) by measuring glomerular filtration rate (51Cr-EDTA technique), blood pressure, and albuminuria. None of the patients were taking drugs other than insulin. Arterial blood pressure, albuminuria, and blood glucose were measured four to eight times/yr, whereas glomerular filtration rate was determined twice yearly. During the median investigation period of 36 (15-66) mo, glomerular filtration rate decreased from 102 +/- 23 to 83 +/- 27 ml.min-1 x 1.73 m-2 (P < 0.001), albuminuria increased from 633 to 1435 micrograms/min (P < 0.001), and blood pressure rose from 133/85 +/- 10/9 to 149/93 +/- 8/11 mmHg (P < 0.001). Univariate analysis revealed a significant correlation between the rates of decline in glomerular filtration rate and diastolic blood pressure (r = 0.52, P < 0.01) and glomerular filtration rate and albuminuria (r = 0.34, P < 0.02). But stepwise multiple linear regression analysis only showed a significant correlation between the rate of decline in glomerular filtration rate and diastolic blood pressure (P < 0.01). In patients with diastolic blood pressure below the mean value of 89 mmHg, stepwise multiple regression analysis showed that albuminuria and not blood pressure was correlated significantly with rate of decline in glomerular filtration rate. Patients were stratified by average value of diastolic blood pressure measured during the investigation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Plasma lipoproteins and renal function during simvastatin treatment in diabetic nephropathy.

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 greater than or equal to 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/l (p less than 0.01), LDL-cholesterol 4.25 vs 2.57 mmol/l (p less than 0.01) and apolipoprotein B 1.37 vs 1.06 mmol/l (p less than 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 (x/divided by antilog SE) is indicated) was 458 (x/divided by 1.58) vs 393 (x/divided by 1.61) and 481 (x/divided by 1.62) vs 368 (x/divided by 1.78 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)

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

Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients.

A prospective study of the prevalence and causes of persistent albuminuria (greater than 300 mg/24 hr) was conducted in non-insulin-dependent diabetic (NIDDM) patients, age less than 66 years, attending a diabetic clinic during 1987. All eligible patients (N = 370) were asked to collect at least one 24-hour urine sample for albumin analysis. Urine collection was obtained in 224 males and 139 females (98%). Fifty patients (7 women) suffered from persistent albuminuria (13.8%). The prevalence of albuminuria was significantly higher in males (19%) than in females (5%). A kidney biopsy was performed in 35 patients (70%). The kidney biopsies revealed diffuse and/or nodular diabetic glomerulosclerosis in 27 patients (77%), while the remaining eight patients (23%) had a variety of non-diabetic glomerulopathies, such as minimal lesion and mesangioproliferative glomerulonephritis. Diabetic retinopathy was present in 15 of 27 patients (56%) with diabetic glomerulosclerosis, while none of the eight patients with a non-diabetic glomerulopathy had retinopathy. Our cross sectional study has revealed a high prevalence of albuminuria and of non-diabetic glomerulopathy as a cause of this complication in NIDDM patients. Presence of diabetic retinopathy strongly suggests that a diabetic glomerulopathy is the cause of albuminuria. Albuminuric non-insulin-dependent diabetic patients without retinopathy require further evaluation, that is, kidney biopsy.

Aged↗
PubMed1992

Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus.

Roughly 40% of all diabetics, whether insulin dependent or not, develop persistent albuminuria, a decline in their glomerular filtration rate, and elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the single most important cause of end-stage renal disease in the Western world, accounting for over one-quarter of all end-stage renal disease. Systemic/glomerular hypertension plays a role in the initiation and progression of diabetic glomerulopathy. Angiotensin-converting enzyme (ACE) inhibitors are superior to conventional antihypertensive drugs in preventing the development of glomerular lesions in insulin-treated streptozotocin diabetic rats. Lowering of glomerular hypertension may be the crucial factor involved. Human studies suggest that ACE inhibitors postpone the progression to clinical overt diabetic nephropathy in normotensive diabetic patients with persistent microalbuminuria. ACE inhibitors combined with a diuretic reduce albuminuria and postpone renal insufficiency in hypertensive diabetics with overt nephropathy. No treatment modality other than antihypertensive treatment has yet been proven to be effective in protecting renal function in diabetic nephropathy. All previous reports dealing with the natural history of diabetic nephropathy have demonstrated a cumulative death rate between 50 and 77% 10 years after the onset of proteinuria. Effective antihypertensive treatment has reduced the cumulative death rate to 15-20% 10 years after the onset of nephropathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy.

Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1, 128 (x/ divided by 3.5) U l-1 and 126 (x/ divided by 3.7) U l-1 (geometric mean (x/ divided by antilog SD)) in group 1, 2, 3 and 4, respectively. 1 U l-1 apo(a) approximates 0.7 mg l-1 Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE: To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN: Open randomised controlled study of four years' duration. SETTING: Outpatient diabetic clinic in tertiary referral centre. PATIENTS: 44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS: The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES: Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS: Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS: The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.

Adolescent↗
PubMed1991

Lack of familial predisposition to cardiovascular disease in type 1 (insulin-dependent) diabetic patients with nephropathy.

A familial predisposition has been proposed as a major determinant of the increased morbidity and mortality from cardiovascular disease demonstrated in Type 1 (insulin-dependent) diabetic patients with nephropathy. We assessed this concept by studying 91 parents of Type 1 diabetic patients with nephropathy and 94 parents of aged-matched Type 1 diabetic patients with normoalbuminuria. The two groups of parents were of a similar age (58 +/- 8 vs 58 +/- 7 years). The prevalence (%) of death and cardiovascular diseases (World Health Organisation questionnaire) was 10 (4-18)% and 12 (6-21)% in parents of nephropathic patients compared to 8 (3-16)% and 13 (6-23)% in parents of normoalbuminuric Type 1 diabetic patients. The frequency of risk factors for cardiovascular disease were about the same in both groups of parents. Microalbuminuria was found in 5% and 11%, hypercholesterolaemia (greater than 6.5 mmol/l) in 25% and 26% and smokers constituted 40% and 34% of parents of patients with and without proteinuria, respectively. A familial predisposition to cardiovascular disease cannot explain the increased morbidity and mortality from cardiovascular disease in young patients with diabetic nephropathy.

Adult↗
PubMed1991

Effect of insulin on renal sodium handling in hyperinsulinaemic type 2 (non-insulin-dependent) diabetic patients with peripheral insulin resistance.

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.min-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 less than 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.m-2, p less than 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 less than 0.01) and in control subjects (1.7 +/- 0.3 vs 0.8 +/- 0.3 ml.min-1.1.73 m-2, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy.

Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we measured the maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR: 51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria, and in 18 sex-, age-, and body mass index-matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Diabetes per se seems to enhance Na+/Li+ countertransport activity.

Antiporters↗
PubMed1991

Blood-retina barrier permeability in diabetes during acute ACE-inhibition.

We assessed the acute effect of ACE-inhibition (captopril) on blood-retina barrier (BRB) permeability in 10 hypertensive insulin-dependent diabetic patients with background retinopathy in a double-masked placebo controlled cross-over study. All patients underwent ophthalmological examination, fundus photography, fluorescein angiography, vitreous fluorometry, and continuous blood pressure recording within 3 h of the drug/placebo administration. The decrease in mean arterial blood pressure, from placebo treatment 149/92 +/- 17/7 to captopril treatment 132/83 +/- 14/7 mmHg (mean +/- SD), P less than 0.01 was not accompanied by a significant decrease in BRB permeability, which was 2.51 (1.24-9.15) with placebo and 3.02 (1.25-13.93).10(-7) cm/s during captopril treatment (geometric mean and-range), NS. Our study suggests that abnormal leakage through the BRB in hypertensive insulin-dependent diabetic patients with background retinopathy is caused predominantly by structural changes in the retinal vessels whereas hydrostatic forces play a minor role.

Adult↗
PubMed1991

Impact of blood pressure and antihypertensive treatment on incipient and overt nephropathy, retinopathy, and endothelial permeability in diabetes mellitus.

Diabetic nephropathy is the main cause of the increased morbidity and mortality in insulin-dependent diabetes mellitus (IDDM) patients. Elevated blood pressure accelerates and effective blood pressure reduction with beta-blockers and/or angiotensin-converting enzyme (ACE) inhibitors delays the progression of nephropathy and reduces albuminuria. All previous reports dealing with the natural history of diabetic nephropathy demonstrated a cumulative death rate between 50 and 77% 10 yr after onset of nephropathy. Effective antihypertensive treatment reduced the cumulative death rate to 15-20% 10 yr after onset of nephropathy. Recent randomized control studies indicate that ACE inhibition may delay and even prevent the development of diabetic nephropathy in normotensive IDDM patients with persistent microalbuminuria. Several cross-sectional and prospective studies suggest an association between elevated blood pressure and the development and progression of diabetic retinopathy. Furthermore, carotid insufficiency or other causes of unilaterally or bilaterally reduced retinal blood flow (pressure) diminish the development of diabetic retinopathy. Diabetic retinopathy is characterized by abnormal leakage of fluorescein through the blood-retinal barrier, an abnormality that can be reversed during antihypertensive treatment. It is well documented that elevated blood pressure, poor metabolic control, and diabetic microangiopathy independently enhance the endothelial leakage of plasma proteins in diabetes mellitus. A link between capillary hypertension, increased extravasation of plasma proteins, and the development and progression of diabetic microangiopathy has been suggested. Blood pressure reduction diminishes the extravasation of plasma proteins. The above results strongly support the case for early and effective treatment of arterial blood pressure elevation in diabetes.

Antihypertensive Agents↗
PubMed1991

Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus.

In normoalbuminuric patients with insulin-dependent diabetes mellitus, plasma atrial natriuretic factor (ANF), cyclic GMP and active renin and the renal clearances of [99Tcm]-diethylenetriaminepentaacetic acid (DTPA) lithium and sodium were studied on a hyperglycaemia day and a euglycaemia day. Baseline euglycaemia was achieved by an overnight variable insulin infusion, which during study days was fixed at the rate necessary to maintain euglycaemia in the morning. After a baseline euglycaemic clearance period of 90 min, measurements were repeated in a new 90-min period beginning 150 min later. On the hyperglycaemia day i.v. infusion of 20% glucose was started at the end of the euglycaemic baseline period, increasing blood glucose (5.3 +/- 1.3 vs 12.1 +/- 1.2 mmol l-1, p less than 0.01). On the euglycaemia day blood glucose declined (5.1 +/- 1.0 vs 4.2 +/- 1.0 mmol l-1, p less than 0.02). Glomerular filtration rate (GFR) was unchanged by acute hyperglycaemia (127 +/- 16 vs 129 +/- 24 ml min-1, NS), but nearly normalized during maintained euglycaemia on the euglycaemia day (124 +/- 17 vs 105 +/- 16 ml min-1, p less than 0.01). When comparing the hyperglycaemic study period with the similarly timed period on the euglycaemia day, GFR was elevated by hyperglycaemia (129 +/- 24 vs 105 +/- 16 ml min-1, p less than 0.01), while the renal clearances of lithium and sodium were similar. Consequently, the calculated absolute proximal reabsorption rate of sodium and water was elevated during hyperglycaemia. Hyperglycaemia reduced the slight decline in plasma concentrations of ANF and cyclic GMP observed on the euglycaemia day. Active renin, glucagon and plasma osmolality were unchanged. In conclusion, marked changes in glomerular filtration rate are induced by changes in blood glucose concentration, but the effect is delayed and thus not directly related to renal tubular transport of glucose. Hyperglycaemia does not affect renal clearances of lithium and sodium, while proximal tubular reabsorption is markedly stimulated. These changes are not related to changes in ANF, renin, glucagon or plasma osmolality.

Adult↗
PubMed1990

Increased blood pressure and erythrocyte sodium/lithium countertransport activity are not inherited in diabetic nephropathy.

Genetic predisposition to essential hypertension, represented by maximal erythrocyte sodium/lithium countertransport activity, has been suggested as a marker for the risk of developing clinical nephropathy in Type 1 (insulin-dependent) diabetes mellitus. To evaluate this hypothesis we measured arterial blood pressure and maximal sodium/lithium countertransport activity of erythrocytes in 80 parents of 49 Type 1 diabetic patients with clinical nephropathy, 78 parents of 49 normoalbuminuric patients and 17 age-matched non-diabetic individuals. The two diabetic groups were carefully matched. In the two groups of parents blood pressure and cell sodium/lithium countertransport activity showed no significant differences (137/83 vs 133/81 mm Hg and 0.33 vs 0.32 mmol/(1 cells x h) respectively). The proportion of parents who had died or received antihypertensive drugs was similar in the two groups. The patients with Type 1 diabetes had significantly higher sodium/lithium countertransport compared to the 39 non-diabetic control subjects independently of the presence or absence of nephropathy (p less than 0.002). However, patients with nephropathy tended to have higher sodium/lithium countertransport activity than normoalbuminuric patients (0.48 vs 0.41 mmol/(1 cells x h), p = 0.06). We conclude that genetic predispositions to essential hypertension and increased maximal erythrocyte sodium/lithium countertransport activity do not appear to be risk markers for the development of clinical nephropathy in Type 1 diabetic patients.

Antiporters↗