Britta Barkeling

Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men

BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite.OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects.DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol·kg−1·min−1) or saline.SUBJECTS: Eight obese (body mass index, BMI, 45.5±2.3 kg/m2) male subjects.MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy fixed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique.RESULTS: Hunger ratings were significantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7±0.5 MJ (21±6%) by GLP-1 infusion (P=0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6±0.35 mmol/L; nadir: 5.3±0.15 mmol/L). No nausea was recorded during GLP-1 infusion.CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this finding might be an increased satiety primarily mediated by gastric vagal afferent signals.

Weight development over time in parous women—The SPAWN study—15 years follow-up

BACKGROUND: Weight gain is common after pregnancy. Most studies suggest that weight gain associated with a pregnancy is between 0.5 and 3.8 kg up to 2.5 y of follow-up. However, 73% of the female patients at our obesity clinic identified pregnancy as an important trigger for marked weight retention. The majority retained more than 10 kg after each pregnancy. The aim of this study was to examine long-term weight development after pregnancy in a 15 y follow-up of women who took part in the Stockholm Pregnancy And Womens Nutrition (SPAWN) study.METHOD AND SUBJECTS: The SPAWN study is a long-term follow-up study of women who delivered children in 1984–85 in Stockholm (n=2342). A total of 1423 participants (response rate=61%) completed questionnaires, which covered eating behaviour and exercise, demographic information including social situation and status and details of the pregnancy before, during and up to 1 y after pregnancy. After 15 y, these women were invited to take part in the follow-up study. Anthropometric measurements and the same questionnaire data were collected from the 563 women who participated (response rate=40%). The sample was divided into two main groups: those who were normal weight before pregnancy and remained normal weight, and those who were normal weight before pregnancy and had become overweight at 15 y follow-up.RESULTS: Those women who became overweight had a higher pre-pregnant body mass index (BMI) (22.3±1.5 vs 20.5±1.6 kg/m2, P<0.001), gained more weight during pregnancy (16.3±4.3 vs 13.6±3.7 kg, P<0.001) and had retained more at 1 y follow-up. The women who became overweight had a steeper weight trajectory gaining more from 1 y follow-up to 15 y follow-up (11.1±6.5 vs 4.5±6.5 kg, P<0.001), with a higher BMI at 15 y follow-up of 27.5±2.6 vs 22.5±2.3 5 kg/m2 (P<0.001). However, differences between those who became overweight and those who did not could not be explained by age, number of children and various socioeconomic factors. Features of pregnancy that did differ between the two groups were breastfeeding and smoking cessation. However, women who became overweight had lower lactation scores than women who remained normal weight. Relatively more subjects of the group that became overweight stopped smoking during pregnancy.DISCUSSION: Pregnancy is a vulnerability factor for some women to become overweight. This study attempted to identify those factors that place initially normal weight women on a steeper weight trajectory as a result of pregnancy. Demographic, behavioural, physical and psychological characteristics only partly explain the weight gain observed at 15 y follow-up. Further research is required to investigate the relative role of these characteristics in predicting postpregnancy weight development.

Natural course of gestational diabetes mellitus: long term follow up of women in the SPAWN study

Objectives Long term follow up women with gestational diabetes mellitus (GDM).

Long‐term weight development after pregnancy

For some women pregnancy is a trigger for developing overweight and obesity. Seventy‐three per cent of 128 female patients at our Obesity Unit indicated that they had retained more than 10 kg after each of their pregnancies, and for this subgroup weight development after pregnancy was of crucial importance for their future health. Although mean weight increases after pregnancy generally are modest, there are wide individual variations. In studies at the Obesity Unit, weight retention ranging from up to 26.5 kg one year after pregnancy to a loss of 12.3 kg was reported, although the mean weight gained was only 0.5 kg. Numerous studies have analysed factors explaining weight development after pregnancy and delivery, with a range of subjects from several hundred thousand women to fewer than one‐hundred, but overall it has been surprisingly difficult to identify strong predictors of weight development. Numerous confounders have been identified; in a review up to 31 such confounders were reported. Methodological problems include weight development over time also in non‐pregnant women and problems of identifying the optimal time‐point when the overall impact of the pregnancy on weight development should be evaluated. Lactation has consistently been found to play a small role in explaining weight retention up to one year after delivery. Few studies have examined the role of physical activity during pregnancy and after delivery to explain weight development. Our own ongoing follow‐up of women who gave birth during 1984–85, the so‐called SPAWN (Stockholm Pregnancy and Women’s Nutrition) study, illustrates that 15 years after delivery, a significant proportion of the 1423 women initially studied were available for re‐examination. Drop‐out analyses indicate that for most variables under study, the remaining women were representative for the initial sample. Pregnancy and weight development are intertwined in a complex pattern, which includes a change in lifestyle factors, such as eating behaviour, physical activity, smoking cessation and degree of lactation, but which are still not fully understood.

Discrepancies between classification systems of childhood obesity

Despite growing concern about weight‐related problems among children, no universally accepted classification system for childhood obesity exists. There is a number of proposed international body mass index (BMI)‐based systems in use and national variants also exist in many countries. The absence of a universally accepted standard and confusion concerning which classification system to use on national levels complicate monitoring of the development of the obesity epidemic, stratification for selective interventions in public health, screening in clinical practice and comparisons between studies. Some proposed international classification systems have not only been recommended for global monitoring and comparisons between studies, but also for clinical and national epidemiological use in some countries. Possible discrepancies may thereby lead to inefficiencies in health care delivery and prevention programmes. The problems associated with misclassification of individuals at risk may lead to overconsumption of health care resources by lower‐risk individuals and underconsumption by higher‐risk individuals, which is costly both in terms of foregone health improvements and in terms of wasteful monetary usage. The aim of this paper was to review the specific problems associated with BMI as a measure of adiposity in childhood, the most commonly used classification systems for childhood obesity based on BMI, and how their performance can be evaluated.

Overconsumption and obesity: Peptides and susceptibility to weight gain

Physiological control of feeding is mediated by tonic and episodic signalling systems. These are sometimes thought of as long-term and short-term control. Tonic signals arise from tissue stores whereas episodic signals oscillate periodically with the consumption of food. These physiological controls are paralleled in the motivation to eat by long-acting enduring traits (such as disinhibition) and by short-acting states (such as hunger). Peptides are usually envisaged to exert an action on appetite control through the modulation of states such as hunger and satiety (fullness). Here we provide evidence that peptides involved in tonic regulation--such as leptin--may express a control over appetite motivation through an effect on traits that confer a constant readiness to eat, whereas episodic peptides such as GLP-1 influence appetite motivation through a state such as hunger. The distinction between tonic and episodic regulation, and between traits and states has implications for understanding overconsumption and the susceptibility to weight gain.

Peptides associated with hyperphagia in adults with Prader–Willi syndrome before and during GH treatment

UNLABELLED Prader-Willi syndrome (PWS) is a complex genetic disorder characterised by mild mental retardation and distinct physical, behavioural, and psychiatric features. One of the cardinal symptoms is excessive eating, which--if left untreated--leads to extreme obesity. In the present study we have examined circulating levels of peptides with documented association to hyperphagia in young adults with PWS. Since growth hormone (GH) is often used nowadays to correct GH insufficiency during childhood PWS, we also studied the impact of GH administration on the peptides. Seventeen adults, 9 men and 8 women, 17-32 years of age with a mean BMI of 35+/-3.2 kg/m(2) participated. All had clinical PWS (Holms criteria). Genetic testing was performed in all patients and in 11 the diagnosis was confirmed. They were randomized to treatment with either placebo or GH (Genotropin, Pharmacia Corporation) for 6 months. Subsequently all received open label treatment to provide all subjects with 12 months active GH treatment. Doses were individually titrated. Weight, BMI, oxytocin (baseline only), leptin, Neuropeptide Y (NPY), and ghrelin were evaluated at baseline and after 6 and 12 months. At baseline plasma mean oxytocin was within and serum ghrelin just above the normal range (14.7+/-1.2 pmol/L and 0.87+/-0.12 microg/L, respectively). Serum leptin levels were high above and plasma NPY levels within the lower normal range (47.8+/-29.1 microg/L and 13+/-1 pmol/L, respectively). Results were independent of genotype. No changes in mean BMI, ghrelin, leptin or NPY were seen following GH treatment. CONCLUSION Leptin levels were in general high reflecting obesity and as a consequence NPY levels were low. In simple obesity oxytocin levels are high, while ghrelin levels are suppressed. In view of the adiposity oxytocin circulated in abnormally low and ghrelin in abnormally high concentrations in our patients. GH treatment of PWS patients did not change ghrelin, leptin or NPY. We suggest that both oxytocin and ghrelin are involved in the pathogenesis of hyperphagia seen in PWS.

A comparison of effects of fish and beef protein on satiety in normal weight men

Background:Previous studies have indicated that fish protein may have a greater effect on satiety compared to other protein sources of animal origin.Objective:To compare the effects of fish protein and beef protein meals on hunger and satiety.Design:Twenty-three normal non-smoking, healthy males aged 20–32 years, body mass index 22.5±1.8 (s.d.) kg/m2 participated in a study, with within-subjects design and 1 week between test days. In the morning of the test days, subjects received a standardized breakfast. Four hours after breakfast, subjects were served an iso-energetic protein-rich (40 energy % protein) lunch meal, consisting of either a fish protein dish or a beef protein dish. Four hours after the start of the lunch meals, an ad libitum standardized evening meal was served and the intake of food was measured. Appetite was rated by visual analogue scales (VAS) immediately before and after the meals, as well as every hour between the meals. After the evening meal until bedtime, subjects were asked to record in detail foods and drinks consumed.Results:The repeated VAS-ratings of hunger, satiety and prospective consumption were modelled in a random effects model, taking pre-lunch VAS-ratings into account. After the fish meal, the point estimates were lower for hunger (−2±4.8), higher for satiety (8.7±6.0) and lower for prospective consumption (−4.9±4.7), but they did not reach statistical significance (P satiety=0.88; P hunger=0.15; P prospective=0.30). However, the energy intake at the evening meal displayed significant differences with subjects eating less after the fish protein lunch (2765 vs 3080 KJ, P<0.01) without feeling less satiated. No later energy compensation after the evening meal was found on the test day.Conclusion:Although no significant differences in VAS-ratings of satiety or hunger were detected, subjects displayed an 11% reduction in energy intake at the subsequent evening meal.

Eating habits in relation to body fatness and gender in adolescents – results from the ‘SWEDES’ study

Objective:To investigate if eating habits among adolescents are related to body fatness and gender.Design:Cross-sectional study.Setting:Obesity Unit, Huddinge University Hospital, Sweden, 2001–2002.Subjects:Two hundred and seventy-five girls and 199 boys, aged 16–17 years.Method:Questionnaires were used for dietary intake and meal frequency, BodPod for measuring body fatness (BF%). In all, 169 girls and 128 boys were classified as adequate reporters (AR) of energy intake, and were used in the dietary analyses. The whole sample was used in the meal frequency analyses.Results:The correlation between reported energy intake and weight in the AR group was 0.23 (P<0.01) for girls and 0.36 for boys (P<0.001). The correlations were inverse or not significant in the whole sample. The following variables correlated significantly with a high BF% (r s=±0.2): a low intake of milk in both girls and boys, a high intake of fibre and alcohol and a low intake of sugar in girls and a low intake of breakfast cereals in boys. Those with regular breakfast habits had healthier food choices than others, but this was not related to BF%. Boys had more meals per day (4.9 vs 4.6, P=0.02), especially early in the morning and late at night, whereas girls reported a higher relative intake of light meals and fruit and a lower intake of milk than boys.Conclusions:A few associations between eating habits and body fatness were found, but without any obvious patterns. The true differences in eating habits between lean and overweight adolescents are probably very small.

Effects of glucocorticoids on leptin levels and eating behaviour in women

Abstract.  Uddén J, Björntorp P, Arner P, Barkeling B, Meurling L, Rössner S (Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden; and Sahlgrens Hospital, Gothenburg, Sweden). Effects of glucocorticoids on leptin levels and eating behaviour in women. J Intern Med 2003; 253: 225–231.