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Biomedical subjects

N Møller

Publications and source records attributed to N Møller.

At least 109 records · Page 6Linked to original sources
PubMed1991

24-h profile of serum osteocalcin in growth hormone (GH) deficient patients with and without GH treatment.

Serum osteocalcin (OC), which is a specific, sensitive, and rapidly responding biochemical bone marker of osteoblastic activity, varies in a circadian rhythm in both normal adults and children with the highest levels during nighttime. In the present study, we characterized the 24-h rhythm of serum OC in 8 growth hormone (GH)-deficient children without treatment, and during two regimens of recombinant human GH (r-hGH), i.e. 2 IU/day s.c. at 08:00 h or at 20:00 h, in comparison with 5 normal, untreated children. Without treatment and when r-hGH was administered at 08:00 h, the 24-h profile of serum OC was correlated with that of the healthy controls in only 1 of 8 patients (r = 0.26 +/- 0.09 (mean +/- SE) and r = 0.10 +/- 0.08) whereas the correlation was significant in 6 of 8 patients (r = 0.44 +/- 0.05) during evening r-hGH administration. Within GH-deficient patients, mean OC level was lower during no r-hGH or evening administration compared with morning administration. In conclusion, untreated GH-deficient children have an abnormal 24-h serum OC profile. Evening administration of 2 IU of r-hGH/day s.c. tends to normalise the 24-h profile but not the average daily level, whereas morning administration of GH increases average daily OC level but does not normalize the circadian rhythm.

Adolescent↗
PubMed1990

Substrate metabolism during modest hyperinsulinemia in response to isolated hyperketonemia in insulin-dependent diabetic subjects.

To assess the metabolic effects of moderate hyperketonemia, six young male type 1 diabetic patients received a 200-minute intravenous (IV) infusion of (1) 0.9 mmol 3-hydroxybutyrate (3-OHB)/kg/h, and (2) saline. To ensure comparable metabolic conditions, a low-dose hyperinsulinemic euglycemic glucose clamp was performed from 5 hours before and throughout 3-OHB/saline infusions. The forearm technique was employed to estimate substrate fluxes in muscle. Infusion of 3-OHB caused: (1) increases (P less than .05) in circulating levels of 3-OHB (from 112 +/- 73 mumol/L to 825 +/- 111 mumol/L) and forearm arteriovenous differences of 3-OHB (from 19 +/- 10 mumol/L to 145 +/- 46 mumol/L), as well as an eightfold increase of plasma acetoacetate. (2) Decreased (P less than .05) levels of nonesterified fatty acids (NEFA; from 466 +/- 85 mumol/L to 201 +/- 14 mumol/L) and glycerol (from 39 +/- 7 mumol/L to 11 +/- 4 mumol/L) and decreased (P less than .05) arteriovenous differences of glycerol (from -16 +/- 8 mumol/L to -3 +/- 2 mumol/L). (3) Increased (P less than .05) levels of serum growth hormone (GH; from 4.1 +/- 1.5 micrograms/L to 15.9 +/- 8.0 micrograms/L). No change was recorded in circulating concentrations of free insulin, glucagon, glucose, lactate, or alanine. Nor were arteriovenous balances of these intermediary metabolites, isotopically determined glucose turnover or amounts of exogenously administered glucose affected. In conclusion, in type 1 diabetic man, the main regulatory effect of isolated hyperketonemia appears to be a direct negative feedback inhibition of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1990

Effects of a growth hormone pulse on total and forearm substrate fluxes in humans.

Under physiological circumstances growth hormone (GH) is secreted in bursts after the onset of sleep and a few hours postprandially. Because most relevant studies have employed constant or repeated infusion of high doses of GH, the possible metabolic effects of such bursts are largely unknown. We have studied seven healthy, male subjects for 7 h after an intravenous bolus of 1) 140 micrograms GH and 2) saline. When injected, serum GH rose to a peak of 21 +/- 3 micrograms/l 10 min after injection. GH caused 1) a rapid, sustained 55% decrease in forearm glucose uptake (P less than 0.05) followed by increases toward control values, 2) a delayed 5 mg/100 ml decrease in plasma glucose (P less than 0.05), and 3) significant 60-250% increases (P less than 0.05) in all measured lipid intermediates (nonesterified fatty acids, 3-hydroxybutyrate, and glycerol) 120-160 min after administration followed by decreases to below control values (P less than 0.05). GH did not influence circulating levels of insulin, C-peptide, glucagon, or insulin-like growth factor I (IGF-I), or isotopically determined glucose turnover. Physiological bursts of GH secretion appear to have acute insulin antagonistic effects with maximal effect on lipolysis after 2 h. These effects are reversed after 4 h. Therefore, GH could play a key role in regulation of diurnal rhythms of substrate levels and fuel utilization in humans.

3-Hydroxybutyric Acid↗
PubMed1990

Pharmacological aspects of growth hormone replacement therapy: route, frequency and timing of administration.

Two or three weekly, daytime intramuscular injections of GH has been the traditional treatment of GH deficiency since the first studies. A recent reevaluation of the feasibility of subcutaneous GH injections revealed no side-effects, but a very strong preference by the patients for the subcutaneous route, and also an increase in growth rate in studies where the patients received daily injections given in the evening. That could indicate that the route, frequency and timing of GH administration may be of clinical importance. Subcutaneous injections result in a slower absorption, a smaller peak value, and a prolonged serum disappearance phase compared to intramuscular injections. This extends the periods of elevated serum GH levels in the patient, which might be advantageous. On the other hand, a reduced bioavailability of GH by the subcutaneous route has also been reported. The frequency of subcutaneous injections correlates positively with growth rate in animal studies. This is commonly ascribed to a closer resemblance to the endogenous pulsatile pattern. However, frequent subcutaneous injections do not induce a pulsatile pattern, but a pattern which is intermediary between continuous and true pulsatile administration. In a short-term patient study, we observed that pulsatile and continuous intravenous administration of GH generated identical increases in serum insulin-like growth factor I, which suggests that both pulsatory and constant, small elevations in serum GH are important for its actions. Concerning the time of administration, evening GH injections yield a more physiological pattern, and it has been shown that evening GH administration induces increased nitrogen retention and is more successful in normalizing circadian patterns of pertinent hormones and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Routes↗
PubMed1990

Evening versus morning injections of growth hormone (GH) in GH-deficient patients: effects on 24-hour patterns of circulating hormones and metabolites.

Since serum GH in normal subjects displays a circadian variation with a major and consistent surge after the onset of sleep we examined whether the time of GH administration in GH-deficient patients had any impact on its action. Eight GH-deficient patients all underwent 3 4-week study schedules in random order: 1) evening (2000 h) sc GH injections, 2) morning (0800 h) sc GH injections, and 3) no GH administration. At the end of each period the patients were admitted to hospital for 24-h measurements of hormones and metabolites. For comparison, 10 age- and sex-matched healthy untreated subjects were hospitalized once under identical conditions. Mean (+/- SE) GH availability, i.e. the area under the curve (AUC; micrograms per L/12 h) for 12 h after injection was significantly greater after evening injection than after morning injections [83.3 +/- 25.4 (evening) vs. 46.0 +/- 10.6 (morning); P less than 0.01]. This might be due to higher skin and sc temperatures when in bed. The 2000-0800 h AUC after evening injection was similar to the corresponding AUC in the reference group. Mean 24-h serum insulin-like growth factor-I levels (micrograms per L) were similar after evening (189.8 +/- 2) and morning (179.5 +/- 5.3) injections (P = 0.8), but the latter displayed a circadian variation suggesting that a steady state had not been reached. Both were significantly lower than the stable reference value (248.4 +/- 3.6 micrograms/L). Blood glucose profiles after morning and evening GH did not differ from that of the reference group, whereas blood glucose decreased when the patients received no GH (P less than 0.01). Daytime (0800-2400 h) insulin levels were increased after morning injections (P less than 0.05). Nighttime levels of lipid intermediates were below normal in the untreated state and after morning injection (P less than 0.05), whereas nighttime blood alanine tended to be above normal after morning GH injection (P = 0.08). Highly significant inverse relationships between circadian lipid intermediates and both blood alanine and lactate concentrations were observed in the reference group and in the patients after evening injections. These relationships disappeared after morning injections. We conclude that the metabolic effects of sc GH injections are clearly influenced by the time of administration and that the closest similarity to normal hormone and metabolite patterns and relationships is reached by GH injection in the evening in GH-deficient patients.

3-Hydroxybutyric Acid↗
PubMed1990

Short-term effects of growth hormone on fuel oxidation and regional substrate metabolism in normal man.

Primarily by increasing the availability of lipid intermediates, GH is likely to have profound effects on substrate consumption rates. To examine the short term actions of GH on glucose turnover, fuel oxidation and regional forearm metabolism, six normal volunteers were each studied twice for 5.5 h after having received a 4-h infusion of GH (20 ng/kg.min) or saline. GH induced slightly falling plasma glucose levels, acute 40-50% decreases in forearm glucose uptake, and no change in glucose turnover. Furthermore, substantial increases in circulating concentrations and forearm uptake of nonesterified fatty acids and 3-hydroxybutyrate were recorded. Although GH infusion was followed by a 50% reduction of forearm alanine release hepatic nitrogen excretion seemed unaffected. Energy expenditure was not influenced by GH, but the non-protein respiratory exchange ratio decreased from a basal value of 0.778 +/- 0.008 to 0.732 +/- 0.007 after GH treatment (P less than 0.05). Correspondingly, lipid oxidation increased from 1.20 +/- 0.06 to 1.48 +/- 0.09 mg/kg.min, and glucose oxidation decreased from 0.97 +/- 0.12 to 0.39 +/- 0.06 mg/kg.min (P less than 0.05). Nonoxidative glucose utilization tended to increase. These data indicate that GH, by promoting lipid utilization and decreasing glucose oxidation, diminishes the need for gluconeogenesis and, therefore, could be protein preserving in the long term. Overall, we found no evidence of GH having acute insulin-like effects on glucose metabolism. GH appears to increase glucose storage, leaving total energy expenditure unaffected.

3-Hydroxybutyric Acid↗
PubMed1990

Pulsatile versus continuous intravenous administration of growth hormone (GH) in GH-deficient patients: effects on circulating insulin-like growth factor-I and metabolic indices.

The episodic and pulsatile nature of GH secretion in normal man is well established. Studies in hypophysectomized rats have indicated that pulsatile administration of GH is superior to continuous infusion in promoting growth, but similar studies have not yet been conducted in human subjects. We compared three different iv GH administration schedules in six GH-deficient patients. They were hospitalized three times for 44 h on three occasions, separated by at least 4 weeks without GH treatment. On each occasion they received 2 IU GH, administered iv as either 1) two boluses (at 2000 and 0200 h), 2) eight boluses (at 3-h intervals starting at 2000 h), or 3) a continuous (2000-0200 h) infusion. Serum insulin-like growth factor-I (IGF-I) after eight boluses and that after continuous infusion were almost identical, with a steep increase reaching a peak at 2000-2400 h, followed by a steady decline. The total areas under the curve, expressed as mean levels (micrograms per L), were 147.6 +/- 11.8 (eight boluses) and 151.2 +/- 8.9 (infusion; P = NS). The change with time in IGF-I after the two-bolus regimen differed significantly from that in the other studies (P less than 0.001), displaying only a modest increase, as also reflected in a smaller area under the curve of serum IGF-I (125.3 +/- 8.7 micrograms/L; P less than 0.05). No differences in blood glucose, serum insulin, or plasma glucagon were observed when comparing the three studies. Both blood glucose and serum insulin tended to be elevated during the second night of each study. Almost identical fluctuations were recorded in lipid intermediates in the three studies, with nightly elevations being more pronounced on the first night. Alanine and lactate exhibited nearly identical patterns in the three studies and were characterized by low nocturnal levels. These data indicate that small but frequent iv boluses and continuous infusion of GH are equally effective in generating an increase in IGF-I in GH-deficient patients, whereas the same amount of GH given as two large boluses results in a significantly smaller increase in IGF-I. This could mean that a prolongation of the period during which serum GH is above zero in GH-treated subjects is just as essential as pulsatility for the growth-promoting effects of the hormone.

3-Hydroxybutyric Acid↗
PubMed1990

Circadian patterns of serum insulin-like growth factor (IGF) II and IGF binding protein 3 in growth hormone-deficient patients and age- and sex-matched normal subjects.

Knowledge of the circadian patterns of serum IGF-II and the large molecular weight IGF binding protein, IGFBP-3 might, apart from its physiological relevance, be of clinical interest, inasmuch as measurements of these parameters are being introduced into the evaluation of GH deficiency. We therefore evaluated the 24-h (08.00-08.00 h) patterns of serum IGF-II and IGFBP-3 in 8 GH-deficient patients who were studied during three periods when receiving 1. GH (2 IU) at 20.00 h; 2. GH (2 1U) at 08.00 h and 3. no GH. For comparison, 10 age- and sex-matched untreated healthy subjects were studied once under similar conditions. The serum IGF-II levels of the patients were relatively stable over the 24-h periods, yielding mean levels which were significantly lower during no GH: 553 +/- 78 (evening GH), 554 +/- 54 (morning GH), and 429 +/- 65 micrograms/l (no GH). The mean IGF-II level in the normal subjects was 635 +/- 29 micrograms/l, which was significantly higher than in either patient study. Similarly, stable 24-h levels of IGFBP-3 were recorded in all studies. The mean IGFBP-3 level of the patients was significantly lower when they received no GH, and the mean level in the healthy subjects was higher than in any of the patient studies: 1853 +/- 301 (no GH), 2755 +/- 317 (evening GH), 2904 +/- 269 (morning GH), and 3856 +/- 186 micrograms/l (healthy subjects). However, minute but significant changes over time, characterised by slight decrements at night, were observed for both parameters in several of the studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Lack of effects of hyperglycemia on the disposal of 3-hydroxybutyrate in insulin-dependent diabetic patients.

There is evidence that hyperketonemia in insulin-dependent diabetes may be aggravated by a decreased disposal rate for ketone bodies. To test the hypothesis that this decrease may be induced by concomitant hyperglycemia through substrate competition at the acetyl-CoA level, 5 young insulin-dependent diabetic subjects received at 2-h iv infusion of 0.9 mmol 3-hydroxybutyrate.kg-1.h-1 at clamped 1. euglycemia (5 mmol/l) and 2. hyperglycemia (11 mmol/l) on separate occasions. To ensure similar metabolic conditions, a low-dose hyperinsulinemic euglycemic clamp was performed during the 5 h preceding the actual studies. Substrate fluxes in muscle were assessed through the forearm technique. The glucose infusion rate was 4.9 and 2.9 mg.kg-1.min-1, and the forearm arteriovenous difference for glucose was 0.72 during hyperglycemia and 0.39 mmol/l (p less than 0.05), during euglycemia. Hyperglycemia did not affect circulating levels of free insulin, glucagon, non-esterified fatty acids, 3-hydroxybutyrate (hyperglycemia: 665, euglycemia: 770 mumol/l, p greater than 0.05) or acetoacetate, nor forearm uptake of 3-hydroxybutyrate (hyperglycemia, 152, euglycemia: 168 mumol/l, p greater than 0.05). In conclusion, our results do not suggest any inhibitory role for hyperglycemia in the disposal of ketone bodies. In as much as extrapolation from the present well insulinized state is appropriate, the data indicate that alternative mechanisms may be involved in the observed impairment of ketone body clearance in hyperketonemic insulin-dependent diabetic patients.

3-Hydroxybutyric Acid↗
PubMed1989

Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man.

To elucidate the short-term actions of growth hormone on insulin sensitivity and forearm metabolism, we have studied six normal male subjects receiving a 6-h hyperinsulinaemic euglycemic clamp with and without a concomitant 4-h growth hormone infusion. When infused, serum growth hormone rose to 25 +/- 4 mU/l and during administration of insulin serum insulin increased by 11 +/- 1 mU/l. During euglycemic clamp, administration of growth hormone decreased forearm glucose uptake after 180 min and onward (240 min 0.216 +/- 0.031 vs 0.530 +/- 0.090 mg/100 ml/min, p less than 0.05). Glucose infusion rate (240 min 2.83 +/- 0.24 vs 4.35 +/- 0.28 mg.kg-1.min-1, p less than 0.05) and glucose disposal rate (240 min 3.57 +/- 0.17 vs 4.00 +/- 0.15 mg.kg-1.min-1, p less than 0.05) also decreased. Growth hormone persistently increased hepatic glucose production after 120 min. After 210 min, all circulating lipid intermediates increased slightly. The decrease in forearm glucose uptake and glucose infusion rate and the increase in hepatic glucose production was observed before there was any detectable increase in circulating levels and forearm uptake of lipid intermediates. These data suggest that growth hormone induces insensitivity to insulin in liver, muscle and fat after 120, 180 and 210 min respectively. The early effects of growth hormone on glucose metabolism seems independent of changes in the rate of lipolysis.

Adult↗
PubMed1989

Metabolic and hormonal responses to exogenous hyperthermia in man.

To study whether hyperthermia reproduces hormonal and metabolic responses seen in stress states such as mild infections, six normal male subjects underwent (i) a 3-h hot bath and (ii) a 3-h thermoneutral control period. During the hot bath body temperature rose by 1.2 +/- 0.03 degrees C (mean +/- SEM) and significant peaks of circulating growth hormone (56 +/- 9 vs 7 +/- 4 mU/l), adrenaline (310 +/- 34 vs 152 +/- 39 pmol/l), glucagon (19.2 +/- 4.3 vs 11.8 +/- 2.3 pmol/l) and cortisol were recorded together with slight hyperinsulinaemia (6.5 +/- 1.3 vs 5.3 +/- 1.0 mU/l, P less than 0.05). Hyperthermia was also accompanied by significant increases in circulating levels of free fatty acids (0.93 +/- 0.1 vs 0.46 +/- 0.1 mmol/l), 3-hydroxybutyrate (196 +/- 67 vs 50 +/- 18 mumol/l), glycerol (102 +/- 10 vs 48 +/- 5 mumol/l) and lactate. Blood alanine decreased and blood glucose remained constant. When an intravenous glucose tolerance test was performed during the last hour of hyperthermia signs of impaired first phase and enhanced second phase insulin responses were recorded. Calculated values for glucose disappearance also deteriorated (1.34 +/- 0.19 vs 2.04 +/- 0.50 %/min, P less than 0.05). We conclude that hyperthermia mimics most major metabolic and hormonal changes observed during mild infection and could provide a model to study these conditions.

Adult↗
PubMed1989

Linkage between serum cholinesterase 2 (CHE2) and gamma-crystallin gene cluster (CRYG): assignment to chromosome 2.

Serum cholinesterase 2 (CHE2) was examined in a Danish material of normal families that has been tested earlier for 70-78 classical marker systems and 25 RFLP systems. DNA for RFLP typing was provided by transforming 16-year-old frozen lymphocytes. The frequency of allele CHE2*C5+ in the Danish population was found to be 0.0430. The highest lod score was between CHE2 and the gamma-crystallin gene cluster (CRYG) (zeta = 4.21 at theta = 0.00 in females). The scores were from a single family with 15 children. CHE2 may, accordingly, be assigned to the location of CRYG: chromosome 2, bands q33-q35.

Blood Grouping and Crossmatching↗
PubMed1988

Effects of the somatostatin analogue SMS 201-995 (sandostatin) on mouth-to-caecum transit time and absorption of fat and carbohydrates in normal man.

1. Somatostatin analogues, such as SMS 201-995 (sandostatin), have been suggested as treatment for a variety of disease states including acromegaly, secretory gastrointestinal tumours and diabetes mellitus. 2. Somatostatin-14 has actions to prolong gastro-intestinal transit time and inhibit intestinal absorption, and we have therefore studied the effects of SMS 201-995 on these processes. Five male subjects received a test meal having been given either saline or 50 micrograms of SMS 201-995 subcutaneously 30 min before ingestion. 3. SMS 201-995 caused a delay in mouth-to-caecum transit time for lactulose assessed by breath hydrogen analysis (316 +/- 17 vs 192 +/- 14 min, mean +/- SEM, P less than 0.01), a delay (234 vs 120 min, P less than 0.05) in the plasma peak of the non-metabolizable glucose analogue 3-O-methylglucose and conversion of the expected postprandial rise in serum triglycerides (with saline 1.02 +/- 0.20 to 1.51 +/- 0.28 mmol/l, P less than 0.05) to a decrease below basal values (with SMS 201-995 0.97 +/- 0.80 to 0.79 +/- 0.11 mmol/l, P less than 0.05). 4. After SMS 201-995, an enhancement of the increase in blood glucose (8.2 +/- 0.7 vs 4.7 +/- 0.2 mmol/l, P less than 0.01) and inhibition and postponement of the postprandial rise in insulin (27.6 +/- 6.7 vs 9.9 +/- 2.1 m-units/l, P less than 0.05) occurred. Furthermore, a rise in non-esterified fatty acids, glycerol and 3-hydroxybutyrate, compared with the decline in concentrations of these metabolites after saline, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
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

Dyslexia and chromosome 15 heteromorphism: negative lod score in a Danish material.

From a large Danish material of random families we selected families with dyslexia as reported by the families themselves and as recorded by a dyslexia institute. Among five "backcross families" studied for chromosome 15 polymorphisms we found only negative lod scores, and at theta = 0.10 a negative score of -3.42; i.e., in our material we did not find any confirmation of the indication of linkage between dyslexia and a chromosome 15 polymorphism found in part of their material by Smith et al. (1983, 1986).

Chromosomes, Human, Pair 15↗
PubMed1986

Linkage of transcobalamin II (TC2) to the P blood group system and assignment to chromosome 22.

The linkage relationships of transcobalamin II (TC2) against 64 other marker systems are studied in a Danish family material (families 604-1505). A strong indication of linkage between TC2 and the blood group system P was discovered (z = 7.91 at theta = 0.14 for males and theta = 0.20 for females combined). Accordingly, TC2 could be assigned to chromosome 22 (since blood group P has earlier been assigned to this chromosome).

Blood Group Antigens↗