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Biomedical subjects

A Astrup

Publications and source records attributed to A Astrup.

At least 37 records · Page 2Linked to original sources
PubMed1998

What do pharmacological approaches to obesity management offer? Linking pharmacological mechanisms of obesity management agents to clinical practice.

Obesity is characterised by pathophysiological defects affecting both sides of the energy balance equation. Individuals with a predisposition to obesity have impaired appetite control when diets are fat-rich and energy dense. They also exhibit a lower than expected resting metabolic rate (RMR). A low RMR, in concert with a sedentary lifestyle, contributes to a low total energy output, which may lead to obesity if continued over a period of years. A low metabolic rate seems to be genetically determined, and is partly caused by low sympathetic nervous system activity. Classical treatment programmes for obesity do not provide a satisfactory long-term outcome for the majority of patients. Patients who achieve only a small weight loss during dietary therapy, and have a tendency to weight regain, are characterised by lower energy expenditure, lower sympathetic activity, and a reduced ability to mobilise fat stores, compared with patients who are more successful at losing weight. It is reasonable to improve or normalise these traits by supporting the dietary approach with pharmacological manipulation of central and peripheral pathways. Agents which stimulate adrenergic neurons are particularly suitable because they offer mechanisms for inhibiting hunger and for stimulating energy expenditure, lipolysis and fat oxidation. Sympathomimetic compounds can reduce appetite and increase energy expenditure. Energy expenditure can be increased by 5-10% via stimulation of a combination of beta-adrenoceptors; beta3-adrenoceptors may predominate during chronic therapy. This increased energy expenditure increases the relative proportion of fat oxidation; as this is not fully compensated by increased energy intake, a negative energy balance occurs. This mechanism may be responsible for the long-term weight loss efficiency of agents like ephedrine/caffeine and sibutramine. Pharmacotherapy can be used to support short-term induction of weight loss or long-term weight maintenance. In the latter case, adrenergic agents enable a greater proportion of patients to maintain a satisfactory weight loss, compared with patients treated with conventional programmes alone. Pharmacotherapy which stabilises the size of fat stores at a lower level contributes indirectly to a pronounced improvement of risk factors, leading to a decreased potential for cardiovascular disease, type 2 diabetes and associated morbidity.

Adrenergic beta-Agonists↗
PubMed1998

Thermogenic effects of sibutramine in humans.

BACKGROUND: Sibutramine is an effective compound for the treatment of obesity, acting both on serotonergic and noradrenergic pathways. Animal studies have shown that sibutramine exerts its effect by enhancing satiety as well as by increasing thermogenesis. OBJECTIVE: We tried to compare the acute thermogenic effect of a single 30-mg dose of sibutramine with placebo on basal energy expenditure (EE) and diet-induced thermogenesis. DESIGN: The study was randomized, double-blind, and placebo controlled. Eleven healthy, normal-weight men underwent 4 distinct treatment regimens separated by washout periods of 6-10 d. EE was measured by indirect calorimetry before and for 5.5 h after sibutramine or placebo administration with or without a 2.1-MJ breakfast. Visual analogue scales for assessment of appetite were completed hourly. RESULTS: Sibutramine caused a significant increase in EE above that for placebo (over 5.5 h) during both the fed (34%, 0.15 kJ/min) and fasted (183%, 0.20 kJ/min) states (P < 0.02) as well as during the last 3.5 h of this 5.5-h period and in the fed (87%, 0.26 kJ/min) and fasted (152%, 0.22 kJ/min) states, respectively (P < 0.01). The sibutramine-induced increase in EE was accompanied by an increase in plasma epinephrine (P < 0.01), heart rate (P < 0.001), blood pressure (P < 0.05), and plasma glucose (P < 0.02). About 25% of the increased heart rate with sibutramine could be explained by increased thermogenesis. Sibutramine increased satiety more than did placebo (5-h area under the curve, P < 0.05). CONCLUSIONS: Sibutramine caused a significant increase in both EE and satiety, which may both contribute to its weight-reducing properties.

Adult↗
PubMed1998

D-Tagatose, a stereoisomer of D-fructose, increases hydrogen production in humans without affecting 24-hour energy expenditure or respiratory exchange ratio.

In growth studies on rats, the ketohexose D-tagatose has been shown to contribute no net metabolizable energy, and a pronounced thermic effect of the sugar has been suggested to account for the absence of energy. In a double-blind and balanced cross-over design, we measured 24-h energy expenditure in eight normal weight humans in a respiration chamber during the consumption of 30 g D-tagatose or 30 g sucrose/d. Metabolic measurements were performed before and after a 2-wk adaptation period with a 30-g daily intake of the test sugar. Total 24-h energy expenditure and hour-by-hour profile were unaffected by the test sugar. The nonprotein respiratory exchange ratio (RERnp) was similar during consumption of D-tagatose and sucrose. However, the effect on RERnp due to CO2 produced by fermentation of D-tagatose could not be quantified in this study. A significant increase in 24-h H2 production (35%) during D-tagatose administration suggests a substantial malabsorption of the sugar. We found no effects of the 2-wk adaptation period on the measured gas exchange variables. Significantly lower fasting plasma insulin and triglyceride concentrations were observed during D-tagatose administration compared with the sucrose period. No effects of D-tagatose on body weight and composition were seen, but the perception of fullness 2.5 h after the sugar load was greater with D-tagatose. In conclusion, this study does not suggest a pronounced thermic effect of D-tagatose, and other mechanisms seem to be required to explain its lack of net energy.

Adult↗
PubMed1998

The American paradox: the role of energy-dense fat-reduced food in the increasing prevalence of obesity.

Although surveys have reported that the fat content of the diet has decreased over past decades, the prevalence of obesity has continued to rise in Europe and North America. This phenomenon, 'the American paradox', has been attributed partly to an inability of the reduction in dietary fat to reduce excess body fat, and partly to the over-consumption of low-fat products, which, despite their reduced fat content, have in some cases been accused of maintaining a high energy density due to low fibre and water contents, and a high content of refined carbohydrates. In Denmark, the prevalence of obesity has increased in a period in which national dietary surveys have reported a reduction of more than 10% in dietary fat content. Analysing the Danish situation, it seems unlikely that the occurrence of the American paradox in Denmark is caused by the increased consumption of energy-dense, low-fat foods. Other explanations, e.g. the under-reporting of dietary fat in surveys and the clustering of obesity-promoting lifestyles in subgroups of the population, should be sought.

Denmark↗
PubMed1998

Fat metabolism in formerly obese women.

An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C). Lipolysis in the periumbilical subcutaneous adipose tissue, whole body energy expenditure (EE), and substrate oxidation rates were measured before, during, and after a 60-min bicycle exercise bout of moderate intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 +/- 1.01 vs. 4.88 +/- 0.74 kJ/min, P < 0.05) but responded similarly to exercise. Adipose tissue glycerol release was twice as high in FO than in C at rest (0.455 +/- 0.299 vs. 0.206 +/- 0.102 mumol.100 g-1.min-1, P < 0.05) but increased similarly in FO and C in response to exercise. Despite higher plasma nonesterified fatty acids (NEFA) in FO (P < 0.001), fat oxidation rates during rest and recovery were lower in FO than in C (1.32 +/- 0.84 vs. 3.70 +/- 0.57 kJ/min, P < 0.02) and fat oxidation for a given plasma NEFA concentration was lower at rest (P < 0.001) and during exercise (P = 0.01) in the formerly obese group. In conclusion, fat mobilization both at rest and during exercise is intact in FO, whereas fat oxidation is subnormal despite higher circulation NEFA levels. The lower resting EE and the failure to use fat as fuel contribute to a positive fat balance and weight gain in FO subjects.

Adipose Tissue↗
PubMed1998

Lower activity of oxidative key enzymes and smaller fiber areas in skeletal muscle of postobese women.

Muscle fiber morphology and activities of four key enzymes, as well as energy metabolism, were determined in nine normal-weight postobese women and nine matched control subjects. No differences in fiber type composition, but a smaller mean fiber area and area of fiber types I and IIb, were found in postobese compared with control subjects (P < 0.05). The activities of beta-hydroxyacyl-CoA dehydrogenase (HADH) and citrate synthase (CS) were 20% lower in postobese than in control subjects (P < 0.05). However, the activities of lactate dehydrogenase and lipoprotein lipase were not significantly different between postobese and control subjects. Basal metabolic rate and respiratory exchange ratio were also similar, but maximal oxygen uptake (VO2 max) tended to be lower in postobese than in control subjects (P = 0.06). When adjustments were made for differences in VO2 max, HADH and CS were not different between postobese and control subjects. In conclusion, these data suggest that smaller fiber areas and lower enzyme activities, i.e., markers of aerobic capacity of skeletal muscle, but not fiber composition, may be factors predisposing to obesity.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1998

Twenty-four-hour respiratory quotient: the role of diet and familial resemblance.

Body weight and obesity show familial resemblance that could be the result of familial correlation of fat oxidation, low levels of which have been implicated in the etiology of weight gain and obesity. We studied the familial correlation of both 24-h respiratory quotient (RQ), an index of the ratio of fat to carbohydrate oxidation, and the possible influence of dietary macronutrient composition expressed by the food quotient (FQ), i.e. the theoretical RQ produced by the diet. We measured the habitual FQ of the 7 days diet by weighed food records, followed by measurement of 24-h RQ in respiration chambers in 71 healthy Caucasian siblings from 31 families. After adjustment for age, gender, and 24-h energy balance, 24-h RQ correlated in families as indicated by an intraclass correlation coefficient (r(i)) of 0.31 (P = 0.03). FQ, adjusted for age and gender, was also a familial trait for the two days immediately preceding diet (r(i) = 0.32, P < 0.01). The familial effect on 24-h RQ, adjusted for age, gender, and 24-h energy balance, remained after adjustment for the FQ of the two days preceding diet (r(i) = 0.27, P < 0.05) and was reduced but not abolished after further adjustment for fasting plasma insulin plus free fatty acids (r(i) = 0.24, P < 0.09). By a correlation analysis aimed at separating familial and individual nonfamilial factors influencing both 24-h RQ and FQ, we found a great but insignificant familial (etaF = 0.49, P < 0.18) and a somewhat lower, but significant individual nonfamilial correlation (etaNF = 0.35, P < 0.03). We conclude that substrate oxidation rates measured by RQ exhibit familial correlation after proper adjustment for confounders such as energy balance, gender, and age, and that this effect could not be fully explained by preceding diet composition, fasting plasma insulin, and free fatty acids. Further RQ and the habitual dietary composition shared familial and nonfamilial factors.

Adult↗
PubMed1998

Sibutramine and energy balance.

Obesity develops from a combination of low energy expenditure and increased energy intake. The current treatment strategy aims at reducing energy intake by a low-fat, high-complex-carbohydrate diet and increasing energy expenditure by increased physical activity. In a major proportion of obese patients, however, this treatment is ineffective and does not produce a satisfactory long-term result. Among the risk factors for weight gain and for an unsuccessful diet-induced weight loss in obese patients is a low metabolic rate, which can be attributed in part to a low sympathetic nervous system (SNS) activity. The low SNS activity may also have an adverse effect on appetite control. Pharmacological enhancement of the SNS may have a role in the normalization of the autonomic control of the disturbed energy balance in obesity. In animal studies, sibutramine causes a negative fat balance and weight loss, by a dual mechanism of action. Sibutramine enhances satiety by a combined noradrenergic and serotonergic effect, thus decreasing food intake. In addition, sibutramine stimulates thermogenesis by activating the SNS. Recent studies have demonstrated that sibutramine also enhances satiety, stimulates thermogenesis and diminishes the weight-loss induced decline in energy expenditure in humans, so the dual effect on energy balance seems to be responsible for the efficient fat loss and weight maintenance found in clinical trials on obese patients. In conclusion, sibutramine can contribute to normalization of the disturbed energy balance in obesity, by enhancing satiety and by the stimulation of energy expenditure.

Adrenal Glands↗
PubMed1998

[Sibutramine, an upcoming drug for weight loss acting on energy consumption and energy expenditure].

Individuals with a low activity of the sympathoadrenal system are at high risk of weight gain and obesity, and obese patients with low sympathetic activity lose less weight on dietary reduction programs. Treatment with sibutramine may be particularly efficient in these patients, because sibutramine normalizes sympathoadrenal activity and thereby stimulates thermogenesis. By a combined stimulation of adrenergic and serotoninergic pathways satiety is enhanced and energy intake is suppressed. This dual effect of sibutramine on energy balance seems to be responsible for the efficient weight loss and improved weight maintenance observed in clinical trials with obese patients. In conclusion, sibutramine can contribute to normalization of the disturbed energy balance in obesity by enhancing satiety and by stimulation of energy expenditure, thereby producing weight loss and an important improvement in risk factor profile and comorbid conditions. Meantime sibutramine is on the market in the United States under the trade name Meridia.

Appetite↗
PubMed1997

Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake.

OBJECTIVES: To compare importance of rate of initial weight loss for long term outcome in obese patients and to compare efficacy of two different weight maintenance programmes. DESIGN: Subjects were randomised to either rapid or slow initial weight loss. Completing patients were re-randomised to one year weight maintenance programme of ad lib diet or fixed energy intake diet. Patients were followed up one year later. SETTING: University research department in Copenhagen, Denmark. SUBJECTS: 43 (41 women) obese adults (body mass index 27-40) who were otherwise healthy living in or around Copenhagen. INTERVENTIONS: 8 weeks of low energy diet (2 MJ/day) or 17 weeks of conventional diet (5 MJ/day), both supported by an anorectic compound (ephedrine 20 mg and caffeine 200 mg thrice daily); one year weight maintenance programme of ad lib, low fat, high carbohydrate diet or fixed energy intake diet (< or = 7.8 MJ/day), both with reinforcement sessions 2-3 times monthly. MAIN OUTCOME MEASURES: Mean initial weight loss and proportion of patients maintaining a weight loss of > 5 kg at follow up. RESULTS: Mean initial weight loss was 12.6 kg (95% confidence interval 10.9 to 14.3 kg) in rapid weight loss group and 12.6 (9.9 to 15.3) kg in conventional diet group. Rate of initial weight loss had no effect on weight maintenance after 6 or 12 months of weight maintenance or at follow up. After weight maintenance programme, the ad lib group had maintained 13.2 (8.1 to 18.3) kg of the initial weight loss of 13.5 (11.4 to 15.5) kg, and the fixed energy intake group had maintained 9.7 (6.1 to 13.3) kg of the initial 13.8 (11.8 to 15.7) kg weight loss (group difference 3.5 (-2.4 to 9.3) kg). Regained weight at follow up was greater in fixed energy intake group than in ad lib group (11.3 (7.1 to 15.5) kg v 5.4 (2.3 to 8.6) kg, group difference 5.9 (0.7 to 11.1) kg, P < 0.03). At follow up, 65% of ad lib group and 40% of fixed energy intake group had maintained a weight loss of > 5 kg (P < 0.07). CONCLUSION: Ad lib, low fat, high carbohydrate diet was superior to fixed energy intake for maintaining weight after a major weight loss. The rate of the initial weight loss did not influence long term outcome.

Adult↗
PubMed1997

The role of low-fat diets and fat substitutes in body weight management: what have we learned from clinical studies?

The introduction of low-fat, high-complex carbohydrate diets far the prevention and treatment of obesity was based on the causal link established between dietary fat and body fatness. Observational and mechanistic studies show that because fat possesses a lower satiating power than carbohydrate and protein, a diet rich in fat can increase energy intake. The propensity to gain weight is enhanced in susceptible persons, particularly sedentary people who have a genetic predisposition to obesity. Low-fat diets cause weight loss proportional to pretreatment body weight in a dose dependent manner; that is, weight loss is correlated positively to the reduction in dietary fat content. A reduction of 10% fat energy produces an average 5-kg weight loss in obese persons. As with traditional caloric counting diets, obese persons lose weight only if they adhere to the prescribed low-fat diet. Failure to achieve a weight loss and to maintain it may be attributed in part to lack of adherence to the diet. After a major weight loss, an ad libitum low-fat diet program appears to be superior to caloric counting in maintaining the weight loss 2 years later. Replacing some fat with protein instead of carbohydrate may increase the weight loss further. Moreover, fat substitutes may make it easier to prevent and treat obesity by making the diet palatable. More randomized, controlled, long-term dietary intervention studies are warranted to identify the optimal diet composition for the treatment of obesity.

Appetite↗
PubMed1997

A method to achieve control of dietary macronutrient composition in ad libitum diets consumed by free-living subjects.

OBJECTIVE: To validate a shop system in controlling macronutrient composition during ad libitum dietary intervention. DESIGN: Six months randomized intervention trial. SETTING: A shop at the department from which all foods were collected free of charge and registered by a purpose-designed computer system. SUBJECTS: Sixty-five free-living obese subjects (25 kg/m2 < BMI < 34 kg/m2) recruited through advertisement and from a waiting list at the Department. Total drop-out rate was 8%. INTERVENTIONS: Ad libitum low-fat diets (30 energy-% (E%) fat): (1) High-protein (25 E% protein, HP) or (2) Low-protein, (12 E% protein, LP) or habitual diet (controls, C). MAIN OUTCOME MEASURES: Compliance was assessed by 24 h urinary nitrogen excretion (24 h UN). RESULTS: After one month of dietary intervention 24 h UN increased significantly in the HP group and decreased significantly in the LP group (Group difference 95% CI):6.8 g (5.0-8.7 g), P < 0.0001). This group difference remained throughout the trial. There was good agreement between protein intake as estimated by the shop computer and as estimated from 24 h UN in both first (r = 0.86) and second half of the intervention (r = 0.80). CONCLUSION: The high dietary compliance demonstrates the potential of this method to control macronutrient composition in ad libitum dietary intervention studies in free-living subjects.

Adolescent↗
PubMed1997

Replacement of dietary fat by sucrose or starch: effects on 14 d ad libitum energy intake, energy expenditure and body weight in formerly obese and never-obese subjects.

OBJECTIVE: To investigate the impact of a high-sucrose diet vs a high-starch and a high-fat diet on 14 d ad libitum energy intake, body weight, energy expenditure and sympathoadrenal activity. MEASUREMENTS: Food intake; body weight and composition (bioelectrical impedance); 24 h energy expenditure, substrate oxidation rates, spontaneous physical activity, heart rate and appetite sensations in a respiration chamber (VAS scores); plasma catecholamine concentration and blood pressure. SUBJECTS: Twenty normal-weight, healthy women, 9 post-obese (body mass index (BMI): 22.9 +/- 0.7 kg/m2) and 11 closely matched controls (BMI: 22.6 +/- 0.4 kg/m2). RESULTS: Average 14 d ad libitum energy intake was 13% and 12% lower on the starch diet compared with the sucrose and fat diets, respectively (P < 0.05). In both post-obese and normal-weight subjects, body weight and fat mass decreased significantly on the starch diet (by 0.7 +/- 0.2 kg and 0.4 +/- 0.1 kg, respectively, P < 0.05). No changes were observed on the fat or sucrose diets. After 14 d on the sucrose diet, 24 h energy expenditure as well as postprandial plasma adrenaline and noradrenaline concentrations, were significantly increased compared with the other two diets. Overall satisfy and palatability ratings were also highest on the sucrose diet. CONCLUSION: Intake of a 14-d ad libitum high-starch diet decreased energy intake and body weight compared with a high-fat or high-sucrose diet. The increased energy expenditure observed on the sucrose-rich diet can probably be explained both by the increased intake of energy and fructose (mainly from sucrose) on this diet.

Adult↗
PubMed1997

Age and sex effects on energy expenditure.

The aims of the present study were to examine possible effects of age and sex on energy expenditure independent of differences in body composition, and to develop prediction equations for individual estimation of energy expenditure. The study is based on 235 female and 78 male subjects ranging in age from 15 to 64 y and with body mass indexes (in kg/m2) ranging from 16.9 to 50.5. Basal metabolic rate (BMR), sleeping energy expenditure, and 24-h energy expenditure were measured with standardized protocols by indirect calorimetry in respiratory chambers. Anthropometric data were also recorded. Spontaneous physical activity (SPA) was estimated by a radar system during the chamber stay. About 90% of the variation in 24-b energy expenditure could be explained by differences in fat-free mass, fat mass, SPA, and duration of exercise (SEM: 526 kJ/d), whereas age and sex did not contribute significantly. When comparing energy expenditure adjusted for body composition and activity between two age groups (20-30 y, n = 98 and 50-65 y, n = 39), BMR was 4.6% lower in the older group (P = 0.04) and there was a tendency toward a lower sleeping energy expenditure in the older group (P = 0.06). No sex difference in any energy expenditure measurement could be found after differences in body composition and activity were taken into account. In conclusion, no sex effect and no linear decrease in energy expenditure was found with increased age and the middle-aged subjects had lower BMR than younger subjects independent of body size, body composition and activity.

Adolescent↗
PubMed1997

Acetylation of or beta-cyclodextrin addition to potato beneficial effect on glucose metabolism and appetite sensations.

Functional foods are gaining more and more interest from health scientists. One way to improve the nutritional properties of foods may be to modify the starch component, often included to stabilize the food product. In this study two chemically modified starches-a 1-2% acetylated potato starch and a starch enriched with 2% beta-cyclodextrin-and a native, unmodified potato starch (control) were investigated with regard to 6-h energy expenditure, substrate metabolism, hormone concentrations, and subjective appetite sensations. Subjects were 11 healthy, normal-weight, young men. The starch (50 g) was prepared as a pudding with fruit sauce and whipped cream (3180 kJ, 49% of energy from carbohydrate, and 40% of energy from fat). The meal was given in the morning after a 2-d carbohydrate-rich, weight-maintenance diet. After the modified-starch meals, response patterns for plasma glucose (P < 0.01), insulin (P < 0.05); gastric inhibitory polypeptide (P < 0.05), subjective satiety (P < 0.05), and fullness (P = 0.06) were significantly different from response patterns after the meal with the control starch. Thus, a flattening of the glucose curve, a lower insulin and gastric inhibitory polypeptide response, and higher fullness ratings were observed after the meal with the beta-cyclodextrin starch. Satiety ratings were higher after both meals with modified starch than after the meal with the control starch. In conclusion, a minor modification insulinemic (1-2%) of native potato starch improved the glycemia, insulinemic, and satiating properties of a meal. This was especially true for the beta-cyclodextrin-enriched starch. Slower gastric-emptying rate or delayed intestinal absorption of the modified starch may explain the observed differences.

Acetylation↗
PubMed1997

Normal levels of energy expenditure in patients with reported "low metabolism'.

The present study examined the hypothesis that patients with apparent diet-resistant obesity have subnormal energy expenditure. Ten biochemically euthyroid patients (eight women and two men), aged 21-76 years, with either excessive gynoid fat distribution or obesity (BMI 23.8-41.0), were referred to the department thought to be suffering from a low metabolic rate syndrome since dietary records showed very low energy intake (< 5 MJ day-1) in combination with failure to lose weight on low-energy diets. Twenty-four-hour energy expenditure (24-h EE), basal energy expenditure (BEE) and sleeping energy expenditure (SEE) were measured in a respiration chamber on a fixed activity programme. The patients consumed a diet containing 37 energy-per cent (E%) fat, 47 E% carbohydrate and 16 E% protein. The individual energy intake was estimated from a previously established algorithm between 24-h EE and fat-free mass (FFM) estimated by bioimpedance. Results were compared with equivalent values in a reference population of 76 subjects ranging from normal weight to obese. No evidence of low metabolism was found in terms of adjusted 24-h EE in the patients with diet resistance when compared with the control group (9263 +/- 819 kJ vs. 9211 +/- 558 kJ). No differences were found when comparing adjusted BEE and SEE in the two groups (7655 +/- 727 vs. 7411 +/- 770 kJ 24 h-1 and 7048 +/- 672 vs. 6911 +/- 408 kJ 24 h-1). The physical activity index (PAI) during the chamber stay was likewise within normal values (1.32 +/- 0.07 vs. 1.34 +/- 0.04; NS).

Adult↗