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Biomedical subjects

H H Parving

Publications and source records attributed to H H Parving.

At least 199 records · Page 11Linked to original sources
PubMed1989

Effect of multiple insulin injections with a pen injector on metabolic control and general well-being in insulin-dependent diabetes mellitus.

The long-term (1) effect of multiple insulin injections in clinical practice was evaluated prospectively in 168 unselected consecutive insulin-dependent diabetic patients, age 31 (10-77) yr, attending a diabetic clinic. All patients received three or more daily injections of short acting insulin using a pen injector (NovoPen) plus one injection of intermediate acting insulin at bedtime. Haemoglobin A1c remained nearly unchanged, baseline: 8.6 (5.7-11.8)%, and after intensified treatment for 12 months: 8.3 (5.7-12.3)%. The frequency of keto-acidosis (0.08 (conventional treatment) versus 0.02 episodes/patient/yr, p less than 0.05) and severe hypoglycaemia (0.69 (conventional treatment) versus 0.38 episodes/patient/yr, p less than 0.005) diminished during intensified treatment. Ninety percent of the patients reported improvement in general well-being and only three percent felt worse. We conclude that multiple insulin injections with a pen injector applied in clinical practice improves general well-being, diminishes the risk of acute metabolic complications, while the overall metabolic control as reflected by haemoglobin A1c remains unaltered.

Adolescent↗
PubMed1989

Morphology of diabetic glomerulopathy and relationship to hypertension.

The mutual relationship between elevated blood pressure and structural changes in the kidney is still an area with more open questions than clear answers. Indirect evidence is available concerning one aspect: When hypertension is present it has a significant impact on the further progression of the structural changes. This evidence is available only in terms of the effect of antihypertensive treatment on the preservation of renal function. Since it has been shown that the demise in renal function in long-term diabetics is closely related to the development of advanced diabetic glomerulopathy, it seems likely that normalization of the blood pressure leads to a slowing of this development. Structural studies to elucidate these interactions are, however, not available. An intriguing question is whether the relationship is interactive also in the other direction. Focusing on the alterations within the glomeruli, the fact is that the glomerulopathy develops over several years before it come to the stage when clinical signs appear. Thus, diabetics with "incipient nephropathy" clearly demonstrate basement membrane (BM) accumulation, showing as increased BM-thickness and increase in mesangial matrix volume. Since this is the most likely point of time for hypertension to develop the necessary condition obtains, that the development of hypertension might be triggered by structural abnormalities in the kidney. The mechanisms of action at this point of time remain speculative. The relationship between structural parameters characterizing diabetic glomerulopathy and the blood pressure level was studied in a series of 14 IDDM patients, representing a span of renal functional impairment. Mean blood pressure in the group was 117 mmHg, with a range from 87-122 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1988

Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy.

STUDY OBJECTIVE: To assess whether long term inhibition of angiotensin converting enzyme with captopril and frusemide or bendrofluazide protects kidney function in diabetic nephropathy. DESIGN: Non-randomised controlled before-after trial of matched hypertensive insulin dependent diabetics with nephropathy treated with captopril and frusemide or bendrofluazide. SETTING: Outpatient diabetic clinic in tertiary referral centre. PATIENTS: Treatment group of 18 hypertensive insulin dependent diabetics with nephropathy (mean age 33), who had not been treated previously. Control group of 13 patients (mean age 32) fulfilling the same entry criteria from a prospective study. INTERVENTIONS: Treatment group was given daily captopril 37.5-100.0 mg and frusemide (mean) 98 mg (10 patients) or bendrofluazide (mean) 4 mg (seven). Treatment was continued for about two and a half years. Controls were not treated. END POINT: Measurement of arterial blood pressure, albuminuria, and glomerular filtration. MEASUREMENTS AND MAIN RESULTS: Baseline values were identical in treated and untreated groups respectively: mean blood pressure 146/93 (SE 3/1) mm Hg v 137/95 (2/1) mm Hg; geometric mean albuminuria 982 (antilog SE 1.2) micrograms/min v 936 (1.2) micrograms/min; and mean glomerular filtration rate 98 (SE 5) ml/min/1.73 m2 v 96 (6) ml/min/1.73 m2. Mean arterial blood pressure fell by 8.7 (1.3) mm Hg with captopril and rose by 6.6 (1.5) mm Hg in controls, (p less than 0.001); Albumin excretion decreased to 390 (1.1) micrograms/min with captopril and rose to 1367 (1.3) micrograms/min in controls (p less than 0.001). The rate of decrease in glomerular filtration rate was lower with captopril (5.8 (0.7) ml/year v 10.0 (1.3) ml/year) (p less than 0.01). Rate of fall in glomerular filtration rate and mean arterial blood pressure were significantly correlated (n = 31, r = 0.37, p less than 0.05). CONCLUSIONS: Captopril is a valuable new drug for treating hypertension in insulin dependent diabetics with nephropathy.

Adult↗
PubMed1988

Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes.

Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years' duration that had started before the age of 41. All eligible patients (n = 982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radioimmunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of less than or equal to 30 mg/24 h (n = 562), microalbuminuria as 31-299 mg/24 h (n = 215), and macroalbuminuria as greater than or equal to 300 mg/24 h (n = 180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1.4%, respectively, in patients with normoalbuminuria, 28% and 5.6% in those with microalbuminuria and 58% and 10.6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%). This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.

Adult↗
PubMed1988

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.

Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mm Hg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 micrograms/min (geometric mean 688 micrograms/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml.min-1. (1.73 m2)-1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open + occluded) was estimated by combined light-and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r = 0.77, p less than 10(-4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r = -0.78, p less than 10(-5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects. Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.

Adult↗
PubMed1988

Effects of acetazolamide on kidney function in type 1 (insulin-dependent) diabetic patients with diabetic nephropathy.

We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a double-blind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection 51Cr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108 +/- 11 vs 82 +/- 9 ml/min, p less than 0.02, diabetic patients: 71 +/- 19 vs 54 +/- 14 ml/min, p less than 0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22 +/- 6 vs 27 +/- 8, NS, diabetic patients: 14 +/- 5 vs 15 +/- 4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one-third (control subjects: 85 +/- 11 vs 56 +/- 7, p less than 0.02, diabetic patients: 55 +/- 17 vs 37 +/- 6, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79 +/- 5 vs 67 +/- 8, p less than 0.02, diabetic patients: 79 +/- 5 vs 72 +/- 6, p less than 0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unchanged. Extracellular fluid volume declined by 10% in both groups (p less than 0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1988

The renin-angiotensin system and kidney function during initial insulin treatment in diabetic man.

Glomerular filtration rate, renal plasma flow, active renin, renin substrate and angiotensin II concentrations were monitored in nine consecutive patients (3 women, 6 men, mean age 31 years) with newly diagnosed, insulin-dependent diabetes. Measurements were performed before and during the initial eight days of intensive insulin treatment. All patients had ketonuria but none had acidosis. Glomerular filtration rate and renal plasma flow were significantly increased at the time of diagnosis as compared with values from normal subjects. A highly significant decline in glomerular filtration rate from 160 +/- 9 (SEM) to 133 +/- 5 ml/min x 1.73 m2 was seen during the initial eight days of treatment (p less than 0.01). Likewise renal plasma flow declined from 601 +/- 33 to 558 +/- 35 ml/min x 1.73 m2 (p less than 0.05). Plasma concentration of renin was within normal range at day 0, and remained unchanged during the eight day study. Also renin substrate concentration was normal and unchanged during the observation period, whereas angiotensin II concentration was low and unchanged. Our study does not support the suggestion that the renin-angiotensin system contributes to the hyperfiltration characteristically found in newly diagnosed insulin-dependent diabetic patients.

Adult↗
PubMed1988

Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy.

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and urinary albumin excretion in incipient diabetic nephropathy (defined as urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) in two out of three sterile ketone-free 24-h urine collections in patients having insulin-dependent diabetes mellitus (IDDM) without hypertension or other kidney disease). The urinary excretion of prostaglandin E2 was significantly elevated in 8 insulin-dependent diabetic patients with incipient nephropathy as compared with 9 normoalbuminuric IDDM patients and 11 healthy controls: 317 (182-1273); 95 (67-225); 132 (54-263) pg/min, respectively (2p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within 2 weeks in 8 females having IDDM with incipient nephropathy. The study design was a randomized double-blind trial with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%) (2p less than 0.01), urinary albumin excretion rate diminished from 207 (63-253) to 87 (49-147) mg/24 h (2p less than 0.01), fractional clearance of albumin declined (70%) (2p less than 0.01). Glomerular filtration rate remained stable (108 (88-133) versus 110 (95-142) ml/min). Blood glucose and blood pressure were comparable during the placebo and indomethacin treatment (12.6 +/- 3 versus 13.4 +/- 5 mmol/l and 122/79 +/- 3/9 versus 122/82 +/- 4/10 mmHg, respectively). Our results suggest that enhanced glomerular synthesis of vasodilating prostaglandins may accelerate microalbuminuria in incipient diabetic nephropathy.

Adult↗
PubMed1987

Effect of antihypertensive treatment on kidney function in diabetic nephropathy.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.

Adult↗
PubMed1987

Effects of indomethacin on kidney function in type 1 (insulin-dependent) diabetic patients with nephropathy.

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albuminuria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253 pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95 pg/min) and 11 non-diabetic women (132 pg/min), respectively (p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized double-blind trial, with the patients receiving either indomethacin (150 mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%, p less than 0.01), glomerular filtration rate diminished from 120 +/- 18 to 106 +/- 17 ml/min/1.73 m2 (p less than 0.05), albuminuria declined from 148 to 69 micrograms/min (median and range) (p less than 0.05) and fractional clearance of albumin diminished 42% (p less than 0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4 +/- 4 versus 14.2 +/- 3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.

Adult↗
PubMed1987

Prevalence and causes of microscopic haematuria in type 1 (insulin-dependent) diabetic patients with persistent proteinuria.

The prevalence and causes of microscopic haematuria were examined in all Type 1 (insulin-dependent) diabetic patients with persistent proteinuria (diabetes duration greater than or equal to 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 greater than or equal to 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 mumol/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.

Adolescent↗
PubMed1987

Strict metabolic control and renal function in the streptozotocin diabetic rat.

Micropuncture studies were made on insulin-treated streptozotocin diabetic rats two weeks after the induction of diabetes and on age-matched control rats. Kidney size, GFR and single nephron GFR were higher in poorly controlled diabetic rats than in normal animals. Single nephron GFR rose as a result of an increase in the hydraulic pressure difference across the glomerular capillary wall caused mainly by a rise in the glomerular capillary pressure due to a diminished ratio of afferent to efferent arteriolar hydraulic resistances. Furthermore, the intratubular pressure was reduced as a result of a decrease in hydraulic resistance in the loop of Henle. Strict metabolic control prevented these changes. In conclusion, the increase in renal function in experimental diabetes is determined by the degree of metabolic control excluding a potential nephrotoxic effect of streptozotocin per se.

Animals↗
PubMed1987

Decreased distensibility of resistance vessels of the skin in type 1 (insulin-dependent) diabetic patients with microangiopathy.

The distensibility of the resistance vessels of the skin at the dorsum of the foot was determined in 11 long-term type 1 (insulin-dependent) diabetic patients with nephropathy and retinopathy, nine short-term type 1 diabetic patients without clinical microangiopathy and in nine healthy non-diabetic subjects. Blood flow was measured by the local 133Xe-xenon washout technique in a vascular bed locally paralysed by the injection of histamine. Blood flow was measured before, during and after a 40 mmHg increase of the vascular transmural pressure, induced by head-up tilt. The mean increase in blood flow during head-up tilt was only 24% in diabetic subjects with and 48% in diabetic patients without clinical microangiopathy, compared with 79% in normal non-diabetic subjects (P less than 0.0005 and P less than 0.05, respectively). An inverse correlation between microvascular distensibility and degree of hyalinosis of the terminal arterioles in biopsies from the skin was demonstrated (r = - 0.57, P less than 0.001). Our results suggest that terminal arteriolar hyalinosis reduces the microvascular distensibility and probably increases the minimal vascular resistance, thereby impeding hyperaemic responses.

Adult↗
PubMed1987

Increased minimal vascular resistance and arteriolar hyalinosis in skin on the leg in insulin-dependent diabetic patients.

Minimal vascular resistance (MVR) was determined in a paralysed cutaneous vascular bed at the dorsum of the foot in diabetic patients. Twelve long-term insulin-dependent diabetic (IDDM) patients with and nine short-term IDDM patients without nephropathy and retinopathy and eight control subjects were investigated. The vascular bed was paralysed by local injection of histamine. Skin perfusion pressure was varied by applying graded external counter pressure over the investigated area. Skin blood flow was measured by the local 99mTc wash-out technique before, during and after three to five step-wise increases of external counter pressure. The MVR was calculated from the reciprocal of the slope of the relationship between blood flow and applied pressure. The MVR was significantly increased in diabetic patients with (mean: 9.3 mmHg ml-1.100 g.min) and without nephropathy and retinopathy (8.5 mmHg ml-1.100 g.min) compared with non-diabetic subjects (5.2 mmHg ml-1.100 g.min) (p less than 0.001 and p less than 0.005, respectively). Diabetic microangiopathy (increased hyalinosis of the basement membranes in the terminal arterioles) was found in skin biopsies in nine of the 12 long-term IDDM patients and in four of the nine short-term IDDM patients, but not in the control subjects. Multiple regression analysis demonstrated a highly significant direct association between MVR and degree of diabetic microangiopathy in the same skin area (p less than 0.0002). A less significant direct association between MVR and arm diastolic blood pressure (p less than 0.05) and blood glucose concentration (p less than 0.05) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Arteriolar hyalinosis does not interfere with the local veno-arteriolar reflex regulation of subcutaneous blood flow in insulin-dependent diabetic patients.

The function of the local nervous veno-arteriolar reflex regulation of blood flow in subcutaneous tissue of the lower leg was studied in diabetic patients. The material comprised 11 long-term insulin-dependent diabetic (IDDM) patients with retinopathy and nephropathy and eight short-term IDDM patients without retinopathy or nephropathy and 11 non-diabetic subjects. The diabetic patients had no or a slight to moderate degree of peripheral autonomic and sensoric neuropathy. Blood flow was measured by the local 133Xe wash-out technique. Blood flow was determined before, during and after an approximately 40 mmHg increase in venous transmural pressure, induced by lowering the lower leg 50 cm below heart level. During lowering of the leg, the subcutaneous blood flow decreased to the same level in long-term IDDM patients (mean: 46%), short-term IDDM patients (53%) and control subjects (53%). There was no association between the relative local blood flow during lowering and the degree of terminal arteriolar hyalinosis studied in skin biopsies from the same tissue area. Our results suggest that terminal arteriolar hyalinosis does not interfere with the local sympathetic-mediated veno-arteriolar reflex regulation of blood flow. Moreover, the vasoconstriction mediated by the veno-arteriolar reflex probably occurs in the larger arterioles (greater than 50-100 micron) or small arteries.

Adult↗