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Biomedical subjects

A Astrup

Publications and source records attributed to A Astrup.

At least 127 records · Page 7Linked to original sources
PubMed1996

Low resting metabolic rate in subjects predisposed to obesity: a role for thyroid status.

A low resting metabolic rate (RMR) for a given body composition has been identified as a risk factor for weight gain and obesity, and has also been reported in formerly obese individuals with the genetic predisposition for obesity. The possible role of thyroid hormone in low RMR was studied in a large sample of postobese women. RMR was measured by indirect calorimetry in 28 weight-stable postobese women with a family history of obesity (PO group) and in a control group of 28 nonobese women closely matched for age, fat mass, and fat-free mass. RMR was 8% lower in the PO than in the control group [[symbol: see text]; 95% Cl:5856 (5520, 6214) compared with 6408 kJ/d (6096, 6768 kJ/d), P < 0.02], and the group difference remained unchanged after fat-free mass and fat mass were adjusted for (552 kJ/d, P < 0.015). The PO group had lower plasma free triiodothyronine [2.4 (1.9, 3.0) compared with 3.4 pmol/L (2.9, 3.9 pmol/L), P < 0.01], whereas plasma androstenedione only tended to be lower in the PO than in the control group. Adjustment for differences in androstenedione did not reduce the difference in RMR, whereas adjustment for differences in plasma free triiodothyronine eliminated the group difference (96 kJ/d, P = 0.59). The present study shows that RMR for a given body composition is lower among postobese than among matched never-obese control subjects. Statistically, the lower plasma free triiodothyronine concentrations of the postobese subjects could explain their lower RMRs, but it remains to be established whether these findings are causally related.

Adult↗
PubMed1996

Twenty-four-hour energy expenditure: the role of body composition, thyroid status, sympathetic activity, and family membership.

The present study assessed the possible familial effect in 71 healthy Caucasian siblings on each of the variables determining the inter-individual variations in energy expenditure (EE) measured under standardized conditions. We found that the 24-h EE measured in respiration chambers of 71 siblings from 32 different families was positively correlated with fat-free mass, which explained 82% of the variation between subjects (P < 0.00001). An additional 10% of the total variation was explained by differences in spontaneous physical activity (P < 0.00001), fat mass (P < 0.00001), plasma concentration of free T3 (P < 0.003), and norepinephrine (P < 0.002), whereas plasma values of epinephrine and androgen hormones did not correlate with 24-h EE. After adjustment for gender, there was a familial aggregation of both 24-h and sleeping EE, as indicated by intraclass correlation coefficients (r) of 0.44 (P < 0.02) and 0.58 (P < 0.01), respectively. The familial effect on gender-adjusted 24-h EE was explained mainly by a familial resemblance of fat-free mass (ri = 0.48; P < 0.015) and fat mass (ri = 0.40; P < 0.03), whereas spontaneous physical activity and plasma concentrations of T2 and norepinephrine did not correlate in families. It is concluded that the familial aggregation of EE in Caucasians is mediated mainly through familial resemblance of body composition; even though plasma concentrations of free T3 and norepinephrine, independent of body composition, explain an additional proportion of the variation in EE, they do not contribute to the familial correlation.

Adult↗
PubMed1996

Long-term effect of dexfenfluramine on amino acid profiles and food selection in obese patients during weight loss.

In depressive disorders an association between basal pre-treatment plasma ratios of tryptophan (Trp) and tyrosine (Tyr) to other large neutral amino acids (LNAA) and the clinical efficacy of serotonergic acting drugs have been established. In order to clarify whether a similar relation exists in obesity and to elucidate the long-term effect of dexfenfluramine (dF) on plasma amino acid profiles and macronutrient selection, we examined 29 obese patients participating in a 12 months double-blind weight loss trial with either dexfenfluramine (dF) (30 mg/day) or placebo (PL) in conjunction with 4.2-5.0 MJ/d diet. Maximum weight loss was obtained after 6 months (dF 12.8 +/- 5.4 kg; PL 13.8 +/- 9.2 kg, x +/- s.d., ns). Plasma Trp/LNAA and Tyr/LNAA were found to be lower than in normal weight controls and were further reduced during treatment (p < 0.05), but without differences between dF and PL groups. Macronutrient selection was not affected by the dF treatment. In the placebo group weight loss was associated with a high pre-treatment energy intake and a high carbohydrate-protein ratio (p < 0.05). A decrease in dietary fat and increase in protein intake (%) and age was found to explain 82% of the variation in weight loss (p < 0.0005), whereas no correlation could be shown in the dF group. Pre-treatment plasma Trp/LNAA or Tyr/LNAA and weight loss were not correlated. In conclusion, neither food selection nor basal plasma amino acid profiles were predictors of weight loss during long-term treatment with dF as an adjuvant to energy restriction, and they were not affected by the drug treatment.

Adult↗
PubMed1996

Determinants of postprandial appetite sensations: macronutrient intake and glucose metabolism.

BACKGROUND: According to the glucostatic theory and the macronutrient balance concept, blood glucose and liver glycogen concentrations are important mediators of hunger and satiety. Results from acute postprandial studies are, however, still conflicting. OBJECTIVE: To investigate the associations between appetite sensations on the one hand and macronutrient intake and measures of glucose metabolism on the other hand. METHODS: Six group-means from three different studies (a total of 64 test meals) were tested in linear regression analyses. RESULTS: Positive correlations were found between delta-mean postprandial satiety and serving weight (r = 0.84, p < 0.05), and carbohydrate content (g) (r = 0.86, p < 0.05) of the meals. Furthermore, delta-mean satiety correlated to delta-AUC for plasma glucose (r = 0.92, p < 0.01), lactate (r = 0.98, p < 0.001), insulin (r = 0.95, p< 0.01), noradrenaline (r = 0.97, p < 0.01), gastric inhibitory polypeptide (r = 0.93), p < 0.01) and net carbohydrate oxidation (r = 0.86, p < 0.05). CONCLUSION: Total serving weight and carbohydrate content of the meals as well as postprandial glucose metabolism seem to be involved in the changes of postprandial hunger and satiety sensations after a meal. Due to the covariation between the single variables it is not possible, however, to distinguish between the different factors involved.

Adult↗
PubMed1995

Pharmacological and clinical studies of ephedrine and other thermogenic agonists.

When given as a supplement to an energy restricted diet the sympathomimetic agent ephedrine, in combination with methylxanthines such as caffeine, improves fat loss by dual actions: a central suppression of appetite and peripheral stimulation of energy expenditure covered by fat oxidation. Mean weight loss was found to be 16.6 kg after 6 months when E+C was given as an adjuvant to an efficient hypoenergetic diet, which was 3.4 kg higher than in the placebo group. An additional 24 weeks treatment with E+C prevented relapse. In the first weeks of treatment E+C offset the hypotensive effect of energy restriction and weight loss, but the effect was transient, and after 8 weeks blood pressures were indistinguishable from those of the placebo group. E+C has no adverse effect on glucose and lipid metabolism, but has been shown to prevent the decline in HDL-cholesterol caused by weight loss. In a comparative trial the weight loss produced by E+C was similar to that of dexfenfluramine. More research on sympathomimetics and methylxanthines should be carried out to identify combinations with improved efficiency and safety. Moreover, more long-term trials and studies in males are required.

Appetite Depressants↗
PubMed1995

Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity.

Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin -dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT) were included in a 12-month, randomized, placebo controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carbohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group differences (mean +/- SD: F, 10.1 +/- 10.0 kg; P, 9.4 +/- 11.5 kg). Fifteen patients from the F group and 14 from the P group completed the 12-month study without weight loss differences. Glycemic regulation improved along with the weight loss, but with a larger decline in plasma C-peptide and fasting glucose levels on the F group (P < .05). Total skeletal muscle glycogen synthase (GS) activity increased by 31% in the F group (P < .01) and by 17% in the P group (nonsignificant) after 6 months of treatment, but was still less than the activity in normal-weight controls (aged 28.0 +/- 6.3 years; body mass index, 23.5 +/- 2.2). After adjustment for fasting glucose, insulin, weight loss, and diabetic state, a positive effect of F remained on the total GS activity, which accounted for 27% of the variation (P < .05). The waist to hip ratio was reduced in P subjects as compared with F subjects (P < .05). Fat-free mass (FFM) tended to be more reduced in the F group as compared with P subjects (4.9 v 1.9 kg), although the difference did not reach statistical significance. In conclusion, F seems to improve insulin sensitivity beyond the effect mediated through weight loss by a possible effect on GS activity in skeletal muscle tissue.

Adult↗
PubMed1995

The reproducibility of subjective appetite scores.

Although subjective appetite scores are widely used, studies on the reproducibility of this method are scarce. In the present study nine healthy, normal weight, young men recorded their subjective appetite sensations before and during 5 h after two different test meals A and B. The subjects tested each meal twice and in randomized order. Visual analogue scale (VAS) scores, 10 cm in length, were used to assess hunger, satiety, fullness, prospective food consumption and palatability of the meals. Plasma glucose and lactate concentrations were determined concomitantly. The repeatability was investigated for fasting values, delta-mean 5 h and mean 5 h values, delta-peak/nadir and peak/nadir values. Although the profiles of the postprandial responses were similar, the coefficients of repeatability (CR = 2SD) on the mean differences were large, ranging from 2.86 to 5.24 cm for fasting scores, 1.36 to 1.88 cm for mean scores, 2.98 to 5.42 cm for delta-mean scores, and 3.16 to 6.44 cm for peak and delta-peak scores. For palatability ratings the CR values varied more, ranging from 2.38 (taste) to 8.70 cm (aftertaste). Part of the difference in satiety ratings could be explained by the differences in palatability ratings. However, the low reproducibility may also be caused by a conditioned satiation or hunger due to the subjects' prior experience of the meals and therefore not just be a reflection of random noise. It is likely, however, that the variation in appetite ratings is due both to methodological day-to-day variation and to biological day-to-day variation in subjective appetite sensations.

Adult↗
PubMed1995

The effect of raw potato starch on energy expenditure and substrate oxidation.

Because resistant starch (RS) is not absorbed as glucose in the small intestine of healthy humans, postprandial thermogenesis should be lower after the intake of RS as compared with digestible starch. To evaluate this hypothesis, we measured 5-h postprandial thermogenesis and substrate oxidation by indirect calorimetry after ingestion of 50 g pregelatinized (0% RS) and 50 g raw potato starch (54% type II RS) in 15 healthy, normal-weight young males. The subjects consumed each starch (mixed in diluted fruit syrup) twice on separate days and in random order. RS intake was followed by lower thermogenesis (46.5 +/- 13.1 compared with 115.4 +/- 10.4 kJ/5 h; P = 0.008), lower glucose oxidation (P < 0.0005), and greater fat oxidation (P = 0.013) than was pregelatinized starch consumption. Our results suggest that RS has no thermogenic effect and that its presence does not influence the size of the thermic response to digestible starch.

Adult↗
PubMed1995

An unusual type of familial lipodystrophy.

A mother and her daughter with a novel type of familial partial lipodystrophy were studied. Both had atrophy of fat in the face, chest, and upper and lower limbs and abdominal obesity caused by intraabdominal fat accumulation. The mother had severe insulin resistance and impaired glucose tolerance, whereas the daughter had normal glucose tolerance and normal insulin sensitivity. Both had metabolic rates about 30% above normal levels, but normal thyroid function and plasma lipids.

Abdomen↗
PubMed1995

Reproducibility of 24-h energy expenditure, substrate utilization and spontaneous physical activity in obesity measured in a respiration chamber.

OBJECTIVE: Determination of within-subject day-to-day coefficients of variations (CV) of 24-h measurements of spontaneous physical activity (SPA), macronutrient oxidation, energy expenditure (EE) and heart rate (HR). DESIGN: Two 24-h measurements in respiration chamber, separated by 14 days of strict weight stability. SUBJECTS: 22 healthy obese subjects, 15 females and seven males (age 27-64 y, BMI: 30-39 kg/m2). MEASUREMENTS: SPA assessed by microwave radar, substrate oxidation and EE measured by indirect calorimetry and heart rate measured by telemetry. RESULTS: For 24-h measurements CV was 0.8% for RQ, 6.7% for fat oxidation, 5.6% for carbohydrate oxidation, 14.5% for protein oxidation, and 4.3% for heart rate. SPA assessed by microwave radar was also reproducible (CV = 9.7%). Within-subject day-to-day coefficients of variations (CV) were 1.5 and 1.8% for 24-h EE and sleeping EE, and 4.1% for RMR. Both on day 1 and 14, 93.4% of the variation in 24-h EE could be explained by differences in fat-free mass (92.3 and 92.4%, respectively) and SPA (1.1 and 1.0%), respectively). Also the algorithm and correlation between 24-h RQ and 24-h energy balance were highly reproducible (r = 0.56, P < 0.01 and r = 0.48, P < 0.05). CONCLUSION: Both macronutrient oxidation, SPA and EE in obese patients can be determined with high reproducibility in a respiration chamber.

Adrenergic beta-Agonists↗
PubMed1995

Prognostic markers for diet-induced weight loss in obese women.

OBJECTIVE: To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women. DESIGN: Dietary intervention consisting of 36 weeks treatment by a 4.2 MJ/d low-fat high carbohydrate diet, and follow-up 2 1/2 years after termination of treatment. SETTING: Outpatient clinic in Copenhagen. SUBJECTS: Forty consecutive female obese patients aged 15 to 62 years. MAIN OUTCOME MEASURE: Weight loss. RESULTS: The maximum weight loss (mean 16.2 kg, 95% CI 14.2-18.2) was positively associated to pre-treatment 24-h energy expenditure (P < 0.01), fat oxidation (%) (P < 0.02), plasma dihydrotestosterone (DHT) (P < 0.01), and to postprandial noradrenaline concentration (P < 0.04). Together these factors could explain 41% of the variation in maximum weight loss. Only 24-h EE and DHT had predictive power on weight loss after 36 weeks. Weight losses in upper and lower tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8 kg (6.2-13.3) (P < 0.02). The adjusted relative risk of losing < 10 kg in the upper compared to the lower DHT tertile was 12% (4-32%). At 2 1/2 y follow-up 21 patients had maintained some of the weight loss (54%), while 14 patients had maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also associated with better weight loss at 2 1/2 y follow-up. CONCLUSION: The study suggests that in particular DHT, but also 24-h EE, fat oxidation, and plasma noradrenaline, may be prognostic markers for weight loss outcome in obese women.

Adolescent↗
PubMed1995

Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans.

OBJECTIVE: To investigate the contribution of beta 3-adrenoceptor activation to sympathetic stimulation of thermogenesis in humans using a sympathomimetic (ephedrine) in combination with a non-selective beta-adrenoceptor antagonist (nadolol). DESIGN: Three doses (2.5, 5 and 10 mg) of nadolol were used to estimate what fraction of the thermogenic response to ephedrine (30 mg) remained after inhibition of beta 1- and beta 2-adrenoceptor mediated responses. SUBJECTS: Nine healthy, young male volunteers at rest after an overnight fast. MEASUREMENTS: Energy expenditure, respiratory quotient, heart rate, blood pressure and plasma potassium, glucose, lactate, glycerol, NEFA and triglycerides were measured before, and for 3 h after treatment with placebo, ephedrine and ephedrine plus three doses of nadolol. RESULTS: Ephedrine produced significant increases in energy expenditure (thermogenesis), heart rate, systolic blood pressure and plasma glucose; the other parameters measured did not change significantly. Nadolol caused significant inhibition of all responses, but 43% of the thermogenic response to ephedrine remained after the 2.5 mg dose of nadolol, whereas the same dose completely inhibited the heart rate and plasma glucose responses. CONCLUSION: All three beta-adrenoceptor subtypes (beta 1, beta 2 and beta 3) may be involved in ephedrine-induced thermogenesis, but the resistance to complete inhibition by the non-selective antagonist nadolol indicates that at least 40% of the response is mediated by an atypical receptor, which is presumed to be the beta 3-adrenoceptor.

Adrenergic beta-Antagonists↗
PubMed1995

Spontaneous weight loss during 11 weeks' ad libitum intake of a low fat/high fiber diet in young, normal weight subjects.

OBJECTIVE: During the first 11 weeks of 8 months' ad libitum intake of a low fat/high fiber diet (25.5 energy-% fat, 58.5 energy-% carbohydrate, 3.9 g dietary fiber/MJ) primarily aimed at investigating the effect on blood lipids, spontaneous, unintended body weight changes occurred. The objective of the present paper was to elaborate the analyses on changes in body weight and composition during the 11 weeks' intervention period. MEASUREMENTS: Dietary intake, body weight and composition. SUBJECTS: Subjects in the intervention (I) (n = 24) and control group (C) (n = 24) were normal weight, young, healthy students. RESULTS: In the intervention group an overall decrease in body weight (-1.3 +/- 0.4 kg) (mean +/- s.e.m.) (P < 0.01) and fat mass (-1.6 +/- 0.2 kg, P < 0.001) occurred. Fat free mass remained unchanged (0.1 +/- 0.3 kg, n.s.). Subjects with the initially lowest level of body fat (n = 10) gained fat-free mass (0.6 +/- 0.2 kg) (n.s.) and lost fat mass (-0.9 +/- 0.2) (P < 0.01). In the intervention group initial body weight and fat mass correlated significantly to change in body weight (r = -0.59, P = 0.003 and r = -0.53, P = 0.008) and fat mass (r = -0.52, P = 0.01, and r = -0.50, P = 0.01). No changes were observed in the control group. CONCLUSION: The ad libitum intake of a low fat/high fiber diet lead to a spontaneous loss of body weight and fat mass in young, normal weight subjects.

Adult↗
PubMed1995

The sympathetic nervous system as a target for intervention in obesity.

The sympathoadrenal system plays an important role in the regulation of both energy intake and energy expenditure (EE), and the sympathetic nervous system (SNS) offers a dual target for pharmacological intervention directed at weight loss in obese patients. The sizes of the fat-free mass and fat mass are the major determinants of resting EE, but studies using different techniques have shown that differences in sympathetic activity can account for an additional proportion of the variation between individuals. Differences in thermogenic responses to food can also be explained by different abilities to activate the sympathoadrenal system. A low resting EE for a given body composition is one manifestation of the genetically determined predisposition to obesity. A low sympathetic activity may be one factor responsible but, as yet, no conclusive evidence has been found. In dietary treatment programmes of obesity, patients with high levels of EE and greater SNS activity achieve greater long-term weight loss than those with lower levels. Pharmacological stimulation with sympathomimetic compounds suppresses appetite and increases energy expenditure through stimulation of beta 1, beta 2, and beta 3-receptor subtypes. During chronic treatment, the beta 3-mediation may predominate due to down-regulation of beta 1- and beta 2-receptors. An improved understanding of the aetiological role of the SNS in the development of obesity in genetically susceptible individuals may permit tailoring of pharmacological intervention.

Energy Metabolism↗
PubMed1994

24-hour energy expenditure and substrate oxidation rates are unaffected by body fat distribution in obese women.

Twenty-four-hour energy expenditure (EE) and nonprotein respiratory quotient (RQnp) were measured by indirect calorimetry in 19 upper-body-obese (UBO) and 15 lower-body-obese (LBO) women with similar body mass index (BMI) and body fat percent. The measurements were performed in a respiration chamber on a predetermined physical activity program and a controlled diet. No differences between the UBO and LBO groups were found in 24-hour, daytime, and sleeping EE after adjustment for differences in fat-free mass (FFM). Furthermore, no group effect was observed in RQnp, but a positive correlation was found between RQnp and age. Despite the fact that an increased free fatty acid (FFA) turnover has been found in UBO subjects, the present study does not support the contention that upper-body obesity is accompanied by an increased lipid oxidation.

Adipose Tissue↗