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Biomedical subjects

H Orskov

Publications and source records attributed to H Orskov.

At least 181 records · Page 10Linked to original sources
PubMed1988

Subcutaneous degradation of biosynthetic human growth hormone in growth hormone deficient patients.

The aim of the present study was to look further into the question of local degradation of sc injected human GH in GH deficient patients. A comparison was made of serum GH levels after constant iv and sc infusion of the same amount of GH (33 ng.kg-1.min-1) in the same 9 GH deficient patients. A 3-h lag period was interposed between the iv and the sc infusion. Iv infusion was continued for 3 h. All 9 subjects subsequently received sc infusion for 19 h and five of them continued for additionally 24 h. The mean steady state serum GH level in the nine patients was 23.1 +/- 5.1 micrograms/l after iv and 6.8 +/- micrograms/l after sc administration (P less than 0.01). Extension of the sc infusion period in 4 of the subjects did not significantly alter the serum GH level (P less than 0.15), implying that a steady state was reached. The GH in the infusion system was stable throughout a 24-h period. We therefore conclude that sc injected GH is degraded locally to a substantial extent.

Adolescent↗
PubMed1988

Low-dose intravenous glucagon has no effect on myocardial contractility in normal man. An echocardiographic study.

In order to investigate the pathophysiological background for the increased cardiac performance described in short-term insulin-dependent diabetes, we infused glucagon intravenously in 8 healthy men at a dose of 5 ng/kg/min for 1 h and at a dose of 10 ng/kg/min for a further hour. Heart rate and blood pressure were measured and myocardial contractility assessed by echocardiography as the fractional shortening of the left ventricle and as the mean circumferential shortening velocity before the glucagon infusion (first base-line level), after the first glucagon infusion period, after the second glucagon infusion period and at 1 h after stopping the glucagon infusion (second base-line level). Plasma levels of glucagon were 79 +/- 15 ng/l, 123 +/- 76 ng/l, 381 +/- 179 ng/l and 77 +/- 22 ng/l, respectively. Heart rate decreased significantly during the first (8%, p less than 0.05) and second (6%, p less than 0.01) glucagon infusion period compared to the mean of the first and the second base-line value. Mean arterial blood pressure, fractional shortening of the left ventricle and mean circumferential shortening velocity were unchanged. We conclude that increments in plasma concentrations of glucagon to levels seen in poorly controlled diabetes does not change myocardial contractility in normal man.

Adult↗
PubMed1988

Increased myocardial contractility during intravenous insulin infusion in type 1 (insulin-dependent) diabetic patients: an echocardiographic study.

On two occasions eight insulin-dependent diabetic patients were connected to an artificial beta-cell, and insulin was administered by continuous intravenous infusion at a rate of 2 mU/kg/min, producing a moderate hyperinsulinaemia (mean 116 microU/ml). At random, blood glucose was kept constant by concomitant glucose infusion, or allowed to decrease to a mean value of 5.3 mmol/l. M-mode echocardiography was performed before, at 90 and at 180 min of insulin infusion. Following the euglycaemic insulin infusion periods, the fractional shortening of the left ventricle increased from 38.2% to 41.0 and 40.2%, respectively (p less than 0.02). The diastolic diameter (pre-load) and end-systolic meridional wall stress (after-load) remained constant in this experiment. In contrast, no change in fractional shortening could be demonstrated during falling blood glucose, possibly because pre-load was altered to a significant degree during this experimental condition. In conclusion, concomitant infusion of insulin and glucose, producing an euglycaemic hyperinsulinaemia, is followed by increased myocardial contractility.

Adult↗
PubMed1988

Increased myocardial contractility following growth hormone administration in normal man. An echocardiographic study.

Cardiac function was studied by echocardiography in 11 normal subjects before subcutaneous growth hormone administration (first control), after one week of subcutaneous growth hormone administration and at one week after stopping subcutaneous growth hormone administration (second control). Plasma growth hormone was 1.4 ng/ml and 4.5 ng/ml, respectively, at the first two examinations. Compared to the first and second control situations heart rate increased by 9% (p less than 0.1) and 15% (p less than 0.01), fractional shortening of the left ventricle by 8% (p less than 0.02) and 9% (p less than 0.01), and mean circumferential shortening velocity by 10% (p less than 0.05) and 14% (p less than 0.01) respectively. Mean arterial blood pressure was unchanged. Thus, in normal man an increase in plasma growth hormone up to levels comparable to those seen in type 1 diabetics during conditions of poor metabolic control seems to be followed by enhancement in myocardial contractility. Therefore we suggest that growth hormone might contribute to the increase of myocardial contractility earlier described in type 1 diabetic patients with no clinical signs of microvascular disease.

Adult↗
PubMed1988

Influence of hyperglycemia on glucose uptake and hepatic glucose production in non-dialyzed uremic patients.

To determine whether the deranged glucose metabolism in uremia, in addition to insulin resistance can be attributed also to reduced glucose-induced glucose uptake, a two-step sequential hyperglycemic clamp (plasma glucose: 120 and 300 mg/dl) was performed in 6 non-dialyzed uremic and 8 healthy subjects. A constant infusion of somatostatin (300 micrograms/h) and soluble insulin (0.2 mU/kg/min) resulted in peripheral serum insulin slightly higher than basal in both uremics (16 +/- 3 and 22 +/- 3 microU/ml; step 1 and 2, respectively) and controls (20 +/- 2 and 22 +/- 1 microU/ml). The glucose-induced glucose uptake (3-3H-glucose) assessed as the difference between step 2 and 1 glucose disposal at the final 30 min of each step was markedly reduced in uremics (3.2 +/- 0.5 mg/kg/min) compared to healthy subjects (5.7 +/- 0.8 mg/kg/min; p less than 0.03). However, the percentage increment in glucose uptake from step 1 to step 2 hyperglycemia was comparable in the two groups (134 +/- 27 and 148 +/- 17%). Modest hyperglycemia (120 mg/dl) and slightly raised insulinemia resulted in comparable suppression of the endogenous (hepatic) glucose production (EGP) in healthy (1.6 +/- 0.2 mg/kg/min) and uremic subjects (1.5 +/- 0.3 mg/kg/min). In controls, pronounced hyperglycemia (300 mg/dl) further reduced EGP (0.6 +/- 0.3 mg/kg/min; p less than 0.01) while EGP in uremics on the contrary tended to rise (2.0 +/- 0.4 mg/kg/min; p = 0.09), thus indicating an abnormal reaction of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Continuous subcutaneous pump infusion of somatostatin analogue SMS 201-995 versus subcutaneous injection schedule in acromegalic patients.

Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201-995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995.

Acromegaly↗
PubMed1987

Greater in vivo than in vitro pulsatility of insulin secretion with synchronized insulin and somatostatin secretory pulses.

To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations.

Animals↗
PubMed1987

CSF somatostatin in multiple sclerosis: reversible loss of diurnal oscillation in relapses.

CSF and venous blood were sampled hourly during 24 hours in 6 control subjects and in 12 patients with MS, 5 of whom were in stable phase and 7 in relapse. CSF somatostatin immunoreactivity was 166 +/- 5.3 (SFM) pg/ml in controls at noon and rose around midnight to 208 +/- 3.8 pg/ml, then decreased to basal levels at about 5 hours and exhibited another small peak 3 hours later. Almost identical patterns were found in patients with MS during stable phase. During relapse, CSF somatostatin was reduced to 99 +/- 9.2 pg/ml and showed no variation from this value. CSF albumin was similar in the three groups and exhibited no fluctuations. Diurnal patterns of serum growth hormone were similar and unrelated to the oscillations in CSF somatostatin, indicating that hypothalamic release was insignificant in the overall production and in variations. The observation that the CNS releases somatostatin at lower levels during relapse in MS and that these do not oscillate may suggest that the constant low contents represent passive spillover from somatostatin-containing neurons, while the undulating levels above them are representative of active, yet unknown neurophysiologic (eg, neurotransmitter) functions which become reversibly extinct in relapse.

Adult↗
PubMed1987

Diurnal plasma profiles of metabolite and hormone concentration in insulin-dependent diabetic patients during conventional insulin treatment and continuous subcutaneous insulin infusion. A controlled study.

In addition to hyperglycaemia, derangement of metabolic and hormonal control may play an important role in the development of microvascular complications in diabetes. Little, however, is known about the impact of insulin pump treatment on metabolic and hormonal parameters. In a 6-month prospective randomized study in insulin-dependent diabetics we therefore investigated the effects of continuous subcutaneous insulin infusion by pump (10 patients) and conventional insulin treatment (10 patients) on the 24-h profiles of blood glucose, glycerol, lactate, 3-hydroxybutyrate, insulin, glucagon and growth hormone by measuring the respective concentrations every 2 h. We found that average blood glucose levels and HbA1c were significantly lower in the group treated by continuous subcutaneous insulin infusion as compared with the group on conventional insulin treatment. Furthermore, we observed an improvement in diurnal levels of lactate and 3-hydroxybutyrate in the pump-treated group which was not seen in the conventionally treated group. A slight increment in alanine was seen in the group treated with insulin pump. Serum growth hormone, glycerol, plasma free insulin as well as the daily insulin supply were unchanged and identical in the two groups. It is noteworthy that in the pump group, the decrease in blood glucose and 3-hydroxybutyrate takes place concomitantly with a significant suppression of glucagon.

3-Hydroxybutyric Acid↗
PubMed1987

Serum profiles and short-term metabolic effect of pituitary and authentic biosynthetic human growth hormone in man. A double-blind cross-over study.

In a double-blind cross-over study we compared pituitary and methionine-free biosynthetic human growth hormone (P-hGH and B-hGH) with respect to pharmacokinetics and short-term metabolic effects in 9 hypopituitary children. They treated themselves for 4 weeks with 2 IU sc daily at 20.00 h. After admittance to hospital 2 IU was given: im the first day, and sc the second. They then switched over to the alternative preparation. The serum profiles of B- and P-hGH were identical. Comparing im and sc absorption, the latter was slower and resulted in smaller areas under the curves, indicating greater local degradation. Both preparations caused identical increases in somatomedin-C, but slightly more sustained after sc injection. Plasma glucose, plasma glucagon, and serum insulin fluctuated within normal ranges. The glucose profile pointed at a modest anti-insulin effect of hGH when given in the morning. The concentration in the blood of lactate, alanine, glycerol and B-OH-butyrate, and in serum of triglyceride, cholesterol and carbamide revealed no abnormalities with either hGH preparation. Finally, no development of anti-GH or E. coli polypeptide antibodies was seen. In conclusion, the pharmacokinetics and short-term metabolic effects of B-hGH and P-hGH were identical.

Adolescent↗
PubMed1987

Plasma growth hormone in acromegalic patients. Demonstration of highly reproducible diurnal profiles in individual patients.

The effects of the selective alpha 2-adrenoreceptor antagonist idazoxan on diurnal variations in plasma growth hormone levels were studied in acromegalic patients. Seven patients entered the study; six patients had been unsuccessfully treated with either pituitary adenotomy, bromocriptine or other drug therapy or a combination of the two procedures. Plasma growth hormone levels were measured at hourly intervals over a period of 24 h under control conditions and following 4 days treatment with either placebo or idazoxan (20 mg po, three times a day); the comparison of idazoxan with placebo was a double blind cross-over study. Except in one patient, the diurnal growth hormone plasma profiles were virtually superimposable under control conditions and following either placebo or idazoxan; each patient had a characteristic profile. Four patients had impressive nocturnal elevations ranging from about 40 to 200 per cent above average daytime levels. Only one had definite paradoxical early postprandial peaks. These observations are contrary to accepted views on growth hormone levels in acromegalic patients. The majority of our patients thus had profiles reminiscent of the normal diurnal plasma growth hormone pattern albeit at a higher level indicating some preserved central drive. The rather high prevalence in the present study of patients having relapses after adenomectomy may indicate that a selection had been made of cases with hypothalamic aetiology. Administration of the selective alpha 2-adrenoreceptor antagonist idazoxan did not modify plasma growth hormone profiles in these patients.

Acromegaly↗
PubMed1987

Increased myocardial performance following acute hyperglycaemia in insulin-dependent diabetic patients. A consequence of increased peripheral blood flow?

Cardiac function during acute hyperglycaemia was investigated by means of echocardiography in eight insulin-dependent (type 1) diabetic patients without microvascular or cardiac disease. Blood glucose was raised from 5.1 +/- 0.8 to 13.0 +/- 0.9 mmol/l for 1 h and then to 20.1 +/- 1.2 mmol/l for 1 h. A saline control study was performed to obtain an equal amount of plasma volume expansion. The left ventricular end-diastolic diameter increased significantly in both studies, however, significantly more following glucose infusion (3.3% at blood glucose of 13.0 mmol/l, 5.4% at blood glucose of 20.1 mmol/l versus 2.7% after both saline infusions). At the blood glucose level of 20.1 mmol/l, fractional shortening of the left ventricle and cardiac output were increased as compared with the baseline level and the level during moderate hyperglycaemia, and also increased compared with values of non-diabetics. In conclusion acute hyperglycaemia is followed by increased myocardial performance, probably as a consequence of increased peripheral blood flow.

Adult↗
PubMed1986

Effects of SMS 201-995 on intermediary metabolism and endocrine status in normal and diabetic humans.

The hormonal and metabolic effects of the somatostatin analogue SMS 201-995 have been examined in normal and diabetic humans. When 50 micrograms of analogue was administered subcutaneously at 8 A.M. and 5:30 P.M., growth hormone secretion over 24 hours was not significantly affected, and the nocturnal growth hormone surge persisted in normal subjects and in type II diabetic patients. Insulin secretion was suppressed in both groups, but glucose tolerance deteriorated only in the normal subjects. Gastrointestinal side effects developed in both groups. Subcutaneous administration of 50 micrograms of SMS 201-995 at 11 P.M. decreased nocturnal growth hormone secretion (peak, 5 +/- 2 milliunits/liter versus 23 +/- 6 milliunits/liter; p less than 0.01) in normal subjects. Postprandial circulating glucose and insulin levels the following day were unaffected by SMS 201-995, and no side effects were observed. In type I diabetic patients receiving a variable rate insulin infusion overnight to maintain normoglycemia, SMS 201-995 (50 micrograms) administered at 11 P.M. decreased insulin requirements for two to three hours after injection. Insulin sensitivity thereafter was unaffected despite suppression of growth hormone secretion. Alternative dosage regimens are necessary to suppress growth hormone release over 24 hours and to minimize side effects in type II diabetes. Administration of the analogue in the late evening suppresses growth hormone secretion overnight, but the "dawn phenomenon" persists in type I diabetic patients.

Blood Glucose↗
PubMed1986

Metabolic abnormalities in children of non-insulin dependent diabetics.

Non-insulin dependent diabetes appears to be an inherited condition. A study of young offspring of non-insulin dependent diabetics was conducted to determine whether metabolic abnormalities could be found at a young age before clinical diabetes developed. Thirteen patients with non-insulin dependent diabetes were selected who fulfilled the following criteria: they had a sibling who also had non-insulin dependent diabetes, their spouse was non-diabetic, and the offspring were aged between 12 and 45 years, not diabetic, and available for study. All 32 offspring had a 75 g oral glucose tolerance test, and results in 13 of them, one randomly selected from each family, were compared with 13 controls of similar age, sex, and weight. The offspring had significantly higher fasting concentrations of glucose, higher proportions of haemoglobin A1, and higher concentrations of insulin, C peptide, and glucagon. After glucose challenge the increases in both glucose and C peptide concentrations were significantly greater in the offspring. These differences were maintained in all 32 offspring when compared with 18 controls of similar age, sex, and weight; seven of the 32 offspring had impaired glucose tolerance. These results indicate that young offspring of selected non-insulin dependent diabetics can show extensive metabolic changes including impaired glucose tolerance. These changes are associated with hyperinsulinaemia and hyperglucagonaemia.

Adolescent↗
PubMed1986

Effects of somatostatin analogue SMS 201-995 in normal man.

Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects.

Adult↗
PubMed1986

Effects of somatostatin analogue SMS 201-995 in non-insulin-dependent diabetes.

The 24-h hormonal and metabolic profiles obtained in five non-insulin-dependent diabetics receiving twice daily s.c. injections of the long-acting somatostatin analogue SMS 201-995 (50 micrograms) have been compared with those obtained following placebo injection. Injections were given 30 min before breakfast and the evening meal. GH secretion was not suppressed by the analogue administered in this manner. Despite suppression of serum insulin levels following breakfast and the evening meal, blood glucose levels were similar during the two study periods with no evidence of worsening in diabetic control. Prolonged suppression of plasma glucagon levels was observed and the nocturnal elevation in serum TSH levels was abolished. Free T4 levels fell significantly following the analogue but total T3 levels were unaffected. Blood alanine levels were elevated throughout the study period following SMS 201-995 but changes in lactate, pyruvate, glycerol and 3-hydroxybutyrate were minor. All five subjects suffered gastrointestinal side-effects. SMS 201-995 (50 micrograms) given twice daily before meals does not cause a deterioration in metabolic control, does not suppress 24-h GH secretion and causes significant side-effects in patients with non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1986

Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency.

The metabolic responses to 4-h infusions of adrenaline (3 micrograms kg-1 h-1) and cortisol (10 mg m-2 h-1 for 2 h followed by 5 mg m-2 h-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 micrograms h-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg-1 h-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11.4 +/- 0.4 mmol l-1, P less than 0.001; somatostatin plus cortisol 6.7 +/- 0.3 mmol l-1, P less than 0.05; somatostatin alone 4.9 +/- 0.4 mmol l-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9.3 +/- 0.4 mmol l-1 v. 7.2 +/- 0.5 mmol l-1 at 45 min, P less than 0.001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0.55 +/- 0.04-1.82 +/- 0.11 mmol l-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2.30 +/- 0.11 mmol l-1 at 60 min, P less than 0.01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗