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Biomedical subjects

H Orskov

Publications and source records attributed to H Orskov.

At least 217 records · Page 12Linked to original sources
PubMed1984

Insulin resistance in uraemic insulin-dependent diabetics. Effect of dialysis therapy as assessed by the artificial endocrine pancreas.

Twenty-four hour insulin requirements were measured in 5 uraemic insulin-dependent diabetics using a glucose controlled insulin infusion system (artificial endocrine pancreas). All patients were studied twice: initially 14 (1-27) days before institution of dialysis treatment and again after a mean of 46 (21-98) days on chronic dialysis therapy. At near normal blood glucose level the daily insulin requirements decreased from 44.8 +/- 2.9 U pre-dialysis to 35.0 +/- 2.3 U post-dialysis (P less than 0.001). The reduction included the prandial as well as the basal requirements. Consistent with this, the mean plasma free insulin level was higher pre-dialysis than post-dialysis (42 +/- 12 microU/ml vs 31 +/- 7 microU/ml) especially during daytime (49 +/- 11 microU/ml vs 37 +/- 9 microU/ml, P less than 0.03), suggesting that a decreased insulin degradation was not a major factor in the difference in insulin requirements. The effect of an acute change in azotaemia on insulin requirements was also evaluated in 4 uraemic diabetics on chronic haemodialysis the day prior to and the day after a routine dialysis (serum creatinine 922 +/- 59 mumol/l vs 555 +/- 109 mumol/l). No difference in insulin administration on the two days was observed (42.5 +/- 6.1 U vs 43.2 +/- 5.6 U). It is concluded that insulin resistance is present in uraemic insulin-dependent diabetics analogous to the insulin resistance widely prevalent in non-diabetic uraemic patients. The abnormality is at least partly reversible after several weeks on chronic dialysis, but not acutely. The pathophysiologic mechanisms underlying the insulin resistance in uraemia in the diabetic remain to be clarified.

Adolescent↗
PubMed1984

Characterization of growth hormone release in response to external heating. Comparison to exercise induced release.

The effects of increases in body temperature on growth hormone (GH)-release were studied in 10 young normal males in the fasting state as well as postprandially. The temperature increase of one degree centigrade was attained by external heating using thermostatically controlled water blankets covered by heat-reflecting aluminium foil. The increase in plasma GH after heating was partially suppressed in the non-fasting state reaching a mean of 7.9 +/- 3.5 (SEM), ng/ml, range 1.0-36 ng/ml. In contrast all subjects exhibited higher increases, mean 18.3 +/- 4.0 ng/ml, range 7-44 ng/ml, in response to heating when fasting. The results were compared in the same subjects to the plasma GH-responses obtained during exercise (450 kpm/min for 40 min) inducing a similar increase in body temperature of about one degree centrigrade. Nevertheless the response in plasma GH (8.4 +/- 3.3 ng/ml, range 0.4-34 ng/ml) was smaller than obtained by the heat test despite a rate of temperature increase on exercise which was about twice as high. Furthermore, the same exercise performed in a cold room under circumstances which precluded any major rises in core temperature resulted in complete inhibition of GH-release. The results indicate that exercise per se does not stimulate GH-secretion, indeed it may inhibit the response expected to be evoked by the exercise-induced rise in temperature. Evidence is also presented that it is core and not cutaneous temperature which modulated GH release. The procedure used for inducing the rise in temperature and plasma GH may be used as a simple, acceptable and safe clinical test for GH-insufficiency.

Adult↗
PubMed1984

Metabolic effects of adrenaline and noradrenaline in man: studies with somatostatin.

The metabolic responses to infusion of adrenaline (6 micrograms/min) and of noradrenaline (5 micrograms/min) for 120 minutes have each been studied in five normal males with and without concurrent somatostatin (250 micrograms/h). Adrenaline induced marked and sustained hyperglycaemia (maximal blood glucose at 75 min, 9.0 +/- 0.4 mmol/l) while noradrenaline induced only a mild and transient blood glucose rise. Blood lactate was elevated by adrenaline (2.57 +/- 0.47 mmol/l with adrenaline, 0.62 +/- 0.06 mmol/l with saline at 120 min, p less than 0.02). Pyruvate levels rose proportionately less so that the circulating lactate:pyruvate ratio was increased (16.6 +/- 1.3 with adrenaline, 11.4 +/- 0.9 with saline at 120 min, p less than 0.05). Lactate and pyruvate levels were unaffected by noradrenaline. Both catecholamines increased circulating non-esterified fatty acid (NEFA) and glycerol to peak at 30 min, while maximal 3-hydroxybutyrate concentrations were achieved at 50 min (0.26 +/- 0.07 mmol/l with adrenaline; 0.23 +/- 0.06 mmol/l with noradrenaline; 0.03 +/- 0.01 mol/l with saline, both p less than 0.05). Insulin levels were partially suppressed by noradrenaline, while a small rise in circulating insulin was observed with adrenaline which was also associated with a large rebound rise in insulin secretion on cessation of the infusion. Mild and transient hyperglucagonaemia was observed with adrenaline while stimulation of glucagon secretion was more sustained with noradrenaline. Somatostatin suppressed insulin, glucagon and growth hormone secretion and both magnified and prolonged the hyperglycaemic effect of adrenaline (maximal at 105 min, 11.3 +/- 0.5 mmol/l, p less than 0.01 versus adrenaline alone).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1983

Carbohydrate and lipid metabolism during continuous ambulatory peritoneal dialysis (CAPD): the effect of a single dialysis cycle.

The effect on hormonal status and intermediary metabolism of a single 6 h dialysis cycle at two different concentrations of dialysate glucose was investigated in six patients on continuous ambulatory peritoneal dialysis. The basal blood glucose level was elevated by 0.5 mmol/l, associated with a threefold increase in basal serum insulin compared with seven normal controls. Blood glucose and serum insulin rose further during dialysis, particularly with hypertonic (215 mmol of glucose/l) dialysis fluid and levels remained high for 6 h after the onset. Plasma glucagon concentrations were 2.7-fold increased and did not decrease to normal during dialysis. Concentrations of the gluconeogenic precursors lactate and alanine were consistently raised, and levels of circulating non-esterified fatty acids and ketone bodies were lowered, particularly with hypertonic dialysis fluid. The long-term effects of sustained hyperinsulinaemia, including suppression of lipolysis and ketogenesis, require further investigation.

Adult↗
PubMed1983

Dopamine blockade inhibits starvation ketosis in man.

The effects of dopamine blockade on the endocrine and metabolic response to starvation have been investigated by administration of metoclopramide, 30 mg daily, or placebo to five normal subjects fasted for sixty hours on two occasions. Blood glucose and alanine concentrations fell with starvation and metoclopramide had no further effect. Concentrations of the other gluconeogenic precursors, lactate and pyruvate, were also unaffected by metoclopramide. The rise in circulating ketone body concentrations with fasting was impaired by metoclopramide, significantly from 44 h onwards (blood total ketone body concentration at 60 h, 3.42 +/- 0.94 mmol/l with placebo; 2.08 +/- 0.67 mmol/l with metoclopramide, P less than 0.05). Blood glycerol and plasma non-esterified fatty acids (NEFA) levels rose with starvation, and metoclopramide had no further effect. Serum insulin concentrations remained low with fasting, while circulating glucagon and growth hormone levels rose. Similar changes were noted with both metoclopramide and placebo. Serum prolactin concentrations during starvation were elevated two to four fold by metoclopramide. The inhibitory effect of dopamine blockade on ketosis thus occurred despite hyperprolactinaemia, and did not result from measurable alterations in insulin, glucagon or growth hormone secretion. The data suggest a stimulatory role for endogenous dopamine on starvation ketonaemia in man.

Acidosis↗
PubMed1983

Metabolic responses to intraduodenal glucose loading in insulin-infused diabetic dogs.

The hormonal and metabolic responses to an intraduodenal glucose load (0.5 g/kg) were first determined in eight normal dogs before diabetes (alloxan/streptozotocin) was induced and then comparison made of the responses to the glucose load when normal plasma glucose profiles were recreated by preprogrammed infusion of insulin via the portal or peripheral circulations. Basal intraportal and peripheral insulin infusions at 0.021 +/- 0.001 and 0.022 +/- 0.000 U . kg-1 . h-1, respectively, for 16 h to fasting diabetic dogs normalized peripheral plasma levels of glucose (5.5 +/- 0.3 and 5.6 +/- 0.6 mmol/liter, respectively), immunoreactive insulin (IRI) (11.5 +/- 1.2 and 16.4 +/- 1.6 microU/ml), glucagon (65 +/- 7 and 62 +/- 5 pg/ml), lactate (0.63 +/- 0.04 and 0.54 +/- 0.03 mmol/liter), and alanine (0.236 +/- 0.037 and 0.191 +/- 0.008 mmol/liter). However, peripheral but not intraportal infusion of insulin depressed levels of glycerol, nonesterified fatty acids (NEFA), and 3-hydroxybutyrate (0.074 +/- 0.006 vs. 0.109 +/- 0.013, P less than 0.01; 0.67 +/- 0.04 vs. 0.84 +/- 0.09, P less than 0.05; and 0.018 +/- 0.004 vs. 0.059 +/- 0.015 mmol/liter, P less than 0.01, respectively). With the preprogrammed insulin infusions used to normalize plasma glucose profiles to the intraduodenal glucose load, all hormonal and metabolic responses were normalized during intraportal infusion (IRI, 72.5 +/- 4.2 microU/ml; glucagon, 66 +/- 10 pg/ml; lactate, 1.06 +/- 0.10 mmol/liter; alanine, 0.251 +/- 0.042 mmol/liter; glycerol, 0.043 +/- 0.013 mmol/liter; NEFA, 0.24 +/- 0.03 mmol/liter; and 3-hydroxybutyrate, 0.012 +/- 0.007 mmol/liter) but marked hyperinsulinemia (103.2 +/- 6.1 microU/ml) and depressed glycerol, NEFA, and 3-hydroxybutyrate responses at 2 h (0.056 +/- 0.005, 0.52 +/- 0.10, and 0.019 +/- 0.010 mmol/liter, respectively) resulted during peripheral infusion. Therefore, only the portal route of insulin infusion achieved complete metabolic normalization during glucose loading in diabetic dogs.

3-Hydroxybutyric Acid↗
PubMed1983

Imitation of normal plasma growth hormone profile by subcutaneous administration of human growth hormone to growth hormone deficient children.

The time course of plasma growth hormone (hGH) levels following sc and im injection of hGH was studied in 12 children with growth hormone deficiency who had received long-term treatment with im injections of highly purified hGH. Also the spontaneous diurnal GH levels in 8 normal children of comparable age were recorded. Blood samples were obtained during 24 h after im and sc injections of 4 IU/m2 hGH and analysed for immunoreactive hGH. While a median peak value of 160 ng/ml (range 135 to 475 ng/ml) was obtained 2 h after im injection, sc injection resulted in a more sustained elevation reaching 41 ng/ml (range 32 to 51 ng/ml) at 6 h subsiding slowly with a median concentration of 15 ng/ml (range 5-24 ng/ml) persisting after 14 h. Gel chromatography demonstrated that the hGH immunoreactivity of blood samples obtained as late as 14 h after sc injection had unaltered molecular size. Seven of the patients were further studied after sc injection of 2 IU/m2 at 20.00 h instead of in the morning. A plasma profile was attained during the night which roughly approximated the average nocturnal plasma pattern of the normal children.

Adolescent↗
PubMed1983

Increased growth rate following transfer to daily sc administration from three weekly im injections of hGH in growth hormone deficient children.

The effect of more frequent (daily) injections of human growth hormone (hGH) on growth rate was studied in 16 growth hormone deficient children (12 boys, 4 girls) during 2 years. All had previously been treated with im injection of hGH 2-3 times weekly and in the majority of the patients a waning growth response was observed. For a total weekly dose of 12 IU hGH a daily dose of 2 IU was injected sc at night before sleep. This dosage has been shown by us to imitate the average nocturnal hGH profile in plasma. Growth response on the im treatment was 5.2 +/- 1.2 cm/year (SD) in boys and 5.4 +/- 0.9 cm/year in girls. A significant increase was seen during the first year of sc treatment to 7.9 +/- 2.7 cm in boys and 6.3 +/- 2 cm in girls. During the second year the growth response was still significantly increased in boys (7.2 +/- 1.9 cm). Bone age was more advanced and the period of previous im treatment was longer in girls (6.7 vs 3.6 years) which may be the main cause of the waning second year response (4.7 +/- 1.3 cm/year). Pubertal development occurred in 9 children during treatment. However, the highest growth rates were not found in these children. Absence of antibodies against hGH and local reactions at the injection site is evidence of the safety of the treatment, which was very well accepted by the children. Daily sc injections thus represent an effective alternative to conventional im injections ensuring high acceptance in children with growth hormone deficiency.

Age Factors↗
PubMed1983

Angiotensin-converting enzyme in diabetes mellitus dependence on metabolic aberration.

Serum angiotensin-converting enzyme (s-ACE) was measured in 56 diabetic outpatients and in 6 juvenile insulin dependent diabetics who developed mild to moderate ketosis after insulin withdrawal. In the outpatients mean s-ACE was increased by 24% compared to healthy controls. However, development of ketosis resulted in significant reduction of s-ACE from 29.2 +/- 1.6 U/ml (+/- SEM) to 23.1 +/- 1.9 U/ml (p less than 0.05). In addition, a clearcut inverse correlation was observed between blood-3-hydroxybutyrate rise and s-ACE decrement (p less than 0.01). The reduction observed may be mediated through the metabolic acidosis.

3-Hydroxybutyric Acid↗
PubMed1983

The glucose sensor. Some results and applications.

This review goes through the development of the glucose-controlled insulin infusion systems. The closed-loop system, Biostator, is described with discussion of demands on technique and function. It deals with the applicability of the glucose sensor in normalizing the diabetic mal-metabolism and selection of any glucose control wanted in experimental situations. The role of the glucose-sensor in clinical use and as a research tool are discussed.

Blood Glucose↗
PubMed1982

The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes: studies with a glucose controlled insulin infusion system (artificial endocrine pancreas).

Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3 +/- 0.7 compared with 5.6 +/- 0.3 mmol/l on feedback control and 5.5 +/- 0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94 +/- 0.04 on subcutaneous insulin, 0.91 +/- 0.04 on feedback control and 0.74 +/- 0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600-1800 h) was normal on feedback control (1.41 +/- 0.20 versus 1.55 +/- 0.18 mg X kg-1 X min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04 +/- 0.09 mg X kg-1 X min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.

Adult↗
PubMed1982

Kidney function and size in type 1 (insulin-dependent) diabetic patients before and during growth hormone administration for one week.

Kidney function and size were studied in seven well-controlled male Type 1 (insulin-dependent) diabetic patients before and after administration of highly purified human growth hormone for one week. Glomerular filtration rate, renal plasma flow (steady state infusion technique with urinary collections using 125I-iothalamate and 131I-hippuran), kidney size (ultrasonic scanning) and urinary excretion rates of albumin and beta-2-microglobulin were measured. Highly purified growth hormone was injected subcutaneously, 2 IU in the morning and 4 IU in the evening. The growth hormone dosage applied induced an elevation in plasma growth hormone concentration from the normal level seen in these very well controlled diabetics to levels within the range previously demonstrated in normally controlled Type 1 diabetic patients. During the week of growth hormone administration, glycaemic control was maintained unchanged by increasing the insulin dose by 79 +/- 9% (mean +/- SEM). Glomerular filtration rate increased from 122 +/- 3 to 131 +/- 3 ml/min X 1.73 m2 (p less than 0.05) and renal plasma flow increased from 535 +/- 10 to 569 +/- 22 ml/min x 1.73 m2 (p less than 0.05). Kidney size changed from 128 +/- 5 to 133 +/- 5 ml/1.73 m2 (NS). Urinary excretion rates of albumin and beta-2-microglobulin were unchanged. The present findings suggest that the growth hormone elevation typically found in Type 1 diabetic patients with reasonable clinical control, contributes to the enhanced glomerular filtration rate and renal plasma flow present in that disease.

Adult↗
PubMed1982

Metabolic interactions of glucagon and cortisol in man--studies with somatostatin.

The metabolic response to pathophysiologic concentrations of glucagon, induced by glucagon infusion, has been examined in normal man before and after 36-60 hr hypercortisolaemia, induced by administration of tetracosactrin-depot. Glucagon alone increased serum insulin levels twofold but blood glucose was unaltered. Plasma NEFA and blood ketone body concentrations were decreased by glucagon infusion. Tetracosactrin produced a threefold rise in serum cortisol levels and caused mild fasting hyperglycemia and hyperinsulinaemia. Subsequent glucagon infusion had no effect on circulating insulin, glucose, NEFA or ketone body concentrations. Simultaneous infusion of somatostatin, to produce partial insulin-deficiency, unmasked a hyperglycemic action of glucagon (+ 3.8 +/- 0.2 mmol/l at 90 min, p less than 0.02). This glucagon-induced rise in blood glucose was diminished by prior tetracosactrin administration. Tetracosactrin revealed a mild lipolytic action of glucagon in partial insulin deficiency, not apparent in the euadrenal state. Glucagon was equally hyperketonemic during somatostatin infusion before and after tetracosactrin. Thus the hyperglycemic and hyperketonemic actions of glucagon at pathophysiologic levels are restricted to insulin deficiency. Hypercortisolaemia reveals a lipolytic action of glucagon in insulin-deficient man but does not potentiate the hyperglycemic or hyperketonemic effects.

Adult↗
PubMed1982

Metabolic effects of cortisol in man--studies with somatostatin.

The metabolic effects of chronic hypercortisolaemia were studied by administration of tetracosactrin-depot, 1 mg I.M. daily for 36-60 hr to normal subjects. Partial insulin and glucagon deficiency were induced at the end of the period by infusion of somatostatin, 100 micrograms/h for 210 min. Tetracosactrin alone induced a three fold rise in basal serum cortisol levels and fasting blood glucose concentration rose from 5.2 +/- 0.2 to 7.2 +/- 0.2 mmole/l (p less than 0.01) with a rise in fasting serum insulin from 5.2 +/- 1.2 to 13.1 +/- 1.9 mU/l (p less than 0.02). Concentrations of the gluconeogenic precursors lactate, pyruvate and alanine were also raised, but non-esterified fatty acid, glycerol and ketone body levels were unchanged. Somatostatin infusion caused a 30%-50% decrease in serum insulin and a 20%-60% decrease in plasma glucagon concentrations both before and after tetracosactrin administration. A similar rise in blood glucose concentration, relative to the saline control, occurred over the period of somatostatin infusion both with and without elevated cortisol levels. However, prior tetracosactrin administration caused a 100% greater rise in blood ketone body concentrations during infusion of somatostatin than was seen in the euadrenal state, despite similar plasma NEFA concentrations. Hypercortisolaemia causes hyperglycaemia and elevated gluconeogenic precursor concentrations but the associated rise in serum insulin concentrations limits lipolysis and ketosis. In insulin deficiency, a ketotic effort of glucocorticoid excess is evident which may be independent of lipolysis and occurs despite concurrent glucagon deficiency. These catabolic actions of cortisol are likely to be of major importance in the metabolic response to stress.

Adult↗
PubMed1982

Hormonal and metabolic changes in hepatic cirrhosis.

The hormonal and metabolic response to 50 g oral glucose has been studied in fifteen patients with hepatic cirrhosis and seven control subjects. Fasting blood glucose concentration was similar in both groups but cirrhotics showed higher glucose levels throughout the glucose tolerance test. Fasting serum insulin concentration was raised in the patient group (0.12 +/- 0.02 vs 0.07 +/- 0.01 nmol/l, p less than 0.05 and hyperinsulinaemia persisted after oral glucose. Blood lactate and pyruvate concentrations were elevated in cirrhotic patients, both fasting and post-glucose, while mean blood lactate correlated with mean serum insulin concentrations (rs 0.55, p less than). Plasma glucagon concentrations although highly variable, did not differ significantly in control and cirrhotic subjects before or after oral glucose. Fasting blood glycerol was increased in the patient group (O.11 +/- 0.01 vs 0.06 +/- 0.01 mmol/l, p less than 0.05) but fasting blood ketone body levels were normal and both glycerol and ketone body concentrations fell normally after glucose. Basal serum cortisol levels were similar in patient and control groups but the expected fall in cortisol concentration found in the control group over the test period was absent in cirrhotics. The hormonal and metabolic abnormalities did not correlate with severity of disease assessed by liver function test and abnormalities were not related to the presence or absence of portal-systemic shunting.

Adult↗