The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

Mechanisms underlying the weight loss effects of RYGB and SG: similar, yet different.

The worldwide obesity epidemic continues unabated, adversely impacting upon global health and economies. People with severe obesity suffer the greatest adverse health consequences with reduced life expectancy. Currently, bariatric surgery is the most effective treatment for people with severe obesity, resulting in marked sustained weight loss, improved obesity-associated comorbidities and reduced mortality. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), the most common bariatric procedures undertaken globally, engender weight loss and metabolic improvements by mechanisms other than restriction and malabsorption. It is now clear that a plethora of gastrointestinal (GI) tract-derived signals plays a critical role in energy and glucose regulation. SG and RYGB, which alter GI anatomy and nutrient flow, impact upon these GI signals ultimately leading to weight loss and metabolic improvements. However, whilst highly effective overall, at individual level, post-operative outcomes are highly variable, with a proportion of patients experiencing poor long-term weight loss outcome and gaining little health benefit. RYGB and SG are markedly different anatomically and thus differentially impact upon GI signalling and bodyweight regulation. Here, we review the mechanisms proposed to cause weight loss following RYGB and SG. We highlight similarities and differences between these two procedures with a focus on gut hormones, bile acids and gut microbiota. A greater understanding of these procedure-related mechanisms will allow surgical procedure choice to be tailored to the individual to maximise post-surgery health outcomes and will facilitate the discovery of non-surgical treatments for people with obesity.

Pharmacologic therapy to induce weight loss in women who have obesity/overweight with polycystic ovary syndrome: a systematic review and network meta-analysis.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are almost three times more likely to be obese than those without PCOS. However, we have no specific interventions to induce weight loss so far and rely on drugs used to treat other symptoms of the syndrome or obesity in the general population. OBJECTIVE: The objective of this study is to compare the effectiveness of metformin, inositol, liraglutide and orlistat to induce weight loss in women with PCOS and overweight/obesity. METHODS: A search was conducted using the MEDLINE, EMBASE, PubMed and CENTRAL databases. Individually randomized, parallel group trials that evaluated the effects of these pharmacological treatments among adults or adolescents with PCOS and overweight/obesity, compared with a placebo or metformin group, were considered eligible. Registration number: PROSPERO CRD 42017076625. RESULTS: Twenty-three trials reporting on 941 women were included in the network meta-analysis. The amount of weight lost differed significantly among the drugs (in descending order): liraglutide, orlistat and metformin. Liraglutide alone, liraglutide/metformin and metformin alone significantly reduced waist circumference, but no change was found with orlistat. Data for waist-to-hip ratio were only available for metformin, which had no significant effect. CONCLUSION: Liraglutide appears superior to the other drugs in reducing weight and waist circumference.

Pre-pregnancy weight loss in women with obesity requesting removal of their intra-uterine contraceptive device in order to conceive: a pilot study of full meal replacement.

Obesity during pregnancy is associated with increased risks of thromboembolism, gestational diabetes, pre-eclampsia, miscarriage, congenital anomaly, macrosomia and stillbirth. The current practice, directed at reducing gestational weight gain, is largely ineffective. The present pilot study was designed to assess the acceptability of a 24-week intensive weight management programme (IWMP; full meal replacement followed by partial meal replacement and weight stabilization) to achieve weight loss for women with obesity requesting removal of their intra-uterine contraceptive device in order to conceive. Twenty six (65%) of eligible participants consented to the IWMP; three received this as routine National Health Service care in the University College Hospital clinic and 14 participated in the study. The commonest reasons for not participating were dislike of milk, anxiety and lack of support from family and friends. Omitting one woman who dropped out because of problems unrelated to the intervention, the completion rate was 46.2%. Including all women who started the programme, mean body mass index decreased significantly (P = 0.005) from 37.8 to 35.3 kg/m2 . The median percentage decrease was significantly (P = 0.007) greater for women who completed the study (14.2) compared to those who dropped out (1.2). These results suggest an impressive level of weight loss in about one third of all women offered the IWMP who had to defer what they were seeking (pregnancy) while following a challenging programme that they were not seeking. However, studies of other interventions, such as partial meal replacement or commercial products, which may have higher rates of completion are still required.

Cost-effectiveness of bariatric surgery in adolescents with severe obesity in the UK.

Evidence shows that surgery for severe obesity in adults improves health and psychological functioning, and is cost-effective. Data on bariatric surgery for adolescents with severe obesity are extremely limited, with no evidence on cost-effectiveness. We evaluated the lifetime cost-effectiveness of bariatric surgery compared with no surgery in adolescents with severe obesity from the UK's National Health Service perspective. Eighteen adolescents with body mass index ≥40 kg m-2 who underwent bariatric surgery (laparoscopic Roux en Y Gastric Bypass [RYGB] [N = 9], and laparoscopic Sleeve Gastrectomy [SG] [N = 9]) at University College London Hospitals between January 2008 and December 2013 were included. We used a Markov cohort model to compare the lifetime expected costs and quality-adjusted life years (QALYs) between bariatric surgery and no surgery. Mean cost of RYGB and SG procedures were £7100 and £7312, respectively. For RYGB vs. no surgery, the incremental cost/QALY was £2018 (95% CI £1942 - £2042) for males and £2005 (95% CI £1974 - £2031) for females. For SG vs. no surgery, the incremental cost/QALY was £1978 (95% CI £1954 - £2002) for males and £1941 (95% CI £1915 - £1969) for females. Bariatric surgery in adolescents with severe obesity is cost-effective; it is more costly than no surgery however it markedly improved quality of life.

Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores.

AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2-year post-surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission. METHODS: A retrospective single-centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression. RESULTS: The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865 (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6 (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12-5.60), P=0.025]. This association became non-significant when adjusted for % weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two-year % weight loss plays a key role in determining diabetes remission.

Calorie restriction and not glucagon-like peptide-1 explains the acute improvement in glucose control after gastric bypass in Type 2 diabetes.

AIMS: To compare directly the impact of glucagon-like peptide-1 secretion on glucose metabolism in individuals with Type 2 diabetes listed for Roux-en-Y gastric bypass surgery, randomized to be studied before and 7 days after undergoing Roux-en-Y gastric bypass or after following a very-low-calorie diet. METHODS: A semi-solid meal test was used to investigate glucose, insulin and glucagon-like peptide-1 response. Insulin secretion in response to intravenous glucose and arginine stimulus was measured. Hepatic and pancreatic fat content was quantified using magnetic resonance imaging. RESULTS: The decrease in fat mass was almost identical in the Roux-en-Y gastric bypass and the very-low-calorie diet groups (3.0±0.3 and 3.0±0.7kg). The early rise in plasma glucose level and in acute insulin secretion were greater after Roux-en-Y gastric bypass than after a very-low-calorie diet; however, the early rise in glucagon-like peptide-1 was disproportionately greater (sevenfold) after Roux-en-Y gastric bypass than after a very-low-calorie diet. This did not translate into a greater improvement in fasting glucose level or area under the curve for glucose. The reduction in liver fat was greater after Roux-en-Y gastric bypass (29.8±3.7 vs 18.6±4.0%) and the relationships between weight loss and reduction in liver fat differed between the Roux-en-Y gastric bypass group and the very-low-calorie diet group. CONCLUSIONS: This study shows that gastroenterostomy increases the rate of nutrient absorption, bringing about a commensurately rapid rise in insulin level; however, there was no association with the large post-meal rise in glucagon-like peptide-1, and post-meal glucose homeostasis was similar in the Roux-en-Y gastric bypass and very-low-calorie diet groups. (Clinical trials registry number: ISRCTN11969319.).

Health literacy: applying current concepts to improve health services and reduce health inequalities.

The concept of 'health literacy' refers to the personal and relational factors that affect a person's ability to acquire, understand and use information about health and health services. For many years, efforts in the development of the concept of health literacy exceeded the development of measurement tools and interventions. Furthermore, the discourse about and development of health literacy in public health and in clinical settings were often substantially different. This paper provides an update about recently developed approaches to measurement that assess health literacy strengths and limitations of individuals and of groups across multiple aspects of health literacy. This advancement in measurement now allows diagnostic and problem-solving approaches to developing responses to identified strengths and limitations. In this paper, we consider how such an approach can be applied across the diverse range of settings in which health literacy has been applied. In particular, we consider some approaches to applying health literacy in the daily practice of health-service providers in many settings, and how new insights and tools--including approaches based on an understanding of diversity of health literacy needs in a target community--can contribute to improvements in practice. Finally, we present a model that attempts to integrate the concept of health literacy with concepts that are often considered to overlap with it. With careful consideration of the distinctions between prevailing concepts, health literacy can be used to complement many fields from individual patient care to community-level development, and from improving compliance to empowering individuals and communities.

Development of a conceptual model of cancer caregiver health literacy.

Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy.

Ghrelin.

BACKGROUND: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism. SCOPE OF REVIEW: In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery. MAJOR CONCLUSIONS: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility and gastric acid secretion, sleep/wake rhythm, reward seeking behavior, taste sensation and glucose metabolism.

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom.

BACKGROUND/OBJECTIVES: The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the 'real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom. SUBJECTS/METHODS: A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed. RESULTS: Patients prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34-1.32). CONCLUSIONS: Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

Regulation of hindbrain Pyy expression by acute food deprivation, prolonged caloric restriction, and weight loss surgery in mice.

PYY is a gut-derived putative satiety signal released in response to nutrient ingestion and is implicated in the regulation of energy homeostasis. Pyy-expressing neurons have been identified in the hindbrain of river lamprey, rodents, and primates. Despite this high evolutionary conservation, little is known about central PYY neurons. Using in situ hybridization, PYY-Cre;ROSA-EYFP mice, and immunohistochemistry, we identified PYY cell bodies in the gigantocellular reticular nucleus region of the hindbrain. PYY projections were present in the dorsal vagal complex and hypoglossal nucleus. In the hindbrain, Pyy mRNA was present at E9.5, and expression peaked at P2 and then decreased significantly by 70% at adulthood. We found that, in contrast to the circulation, PYY-(1-36) is the predominant isoform in mouse brainstem extracts in the ad libitum-fed state. However, following a 24-h fast, the relative amounts of PYY-(1-36) and PYY-(3-36) isoforms were similar. Interestingly, central Pyy expression showed nutritional regulation and decreased significantly by acute starvation, prolonged caloric restriction, and bariatric surgery (enterogastroanastomosis). Central Pyy expression correlated with body weight loss and circulating leptin and PYY concentrations. Central regulation of energy metabolism is not limited to the hypothalamus but also includes the midbrain and the brainstem. Our findings suggest a role for hindbrain PYY in the regulation of energy homeostasis and provide a starting point for further research on gigantocellular reticular nucleus PYY neurons, which will increase our understanding of the brain stem pathways in the integrated control of appetite and energy metabolism.

Building equity in chronic disease management in Thailand: a whole-system provincial trial of systematic, pro-active chronic illness care.

Thailand has a history of implementing innovative and proactive policies to address the health needs of its population. Since 1962 Thailand has implemented initiatives that led to it having a health system characterized by a primary care focus, decentralization and mechanisms to maximize equity and universal access to basic care at the local level. Thai health structures initially evolved to meet challenges including infectious and developmental diseases and later HIV. Early in the 21st century chronic illness rapidly became the greatest cause of morbidity and mortality and the question has arisen how Thailand can adapt its strong health system to deal with the new epidemics. This article describes an effort to reorient provincial health services to meet the needs of the increasing number of people with diabetes and heart disease. It describes measures taken to build on the equity-promoting elements of the Thai health system. The project included; a situational analysis, development and implementation of a chronic disease self-management intervention implemented by nurses and alignment of provincial health services. The self-management intervention is currently being evaluated within a clustered randomized control trial. The evaluation has been developed to fit with the focus on equity in relation to both selection criteria and the outcomes that are being assessed.

Attenuated peptide YY release in obese subjects is associated with reduced satiety.

The responses of the gut hormone peptide YY (PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a graded rise in plasma PYY (R2 = 0.96; P < 0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P < 0.05 at all levels). The ratio of plasma PYY(1-36) to PYY(3-36) was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY(3-36) was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY(3-36) in humans caused a graded reduction in food intake (R2 = 0.38; P < 0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY(3-36) on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY(3-36). Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY(3-36) infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.

Peptide YY: a potential therapy for obesity.

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.

Pancreatic polypeptide reduces appetite and food intake in humans.

Pancreatic polypeptide (PP) is a gut hormone released from the pancreas in response to ingestion of food. Plasma PP has been shown to be reduced in conditions associated with increased food intake and elevated in anorexia nervosa. In addition peripheral administration of PP has been shown to decrease food intake in rodents. These findings suggest that PP may act as a circulating factor that regulates food intake. Therefore we investigated the effect of intravenous infusion of PP (10 pmol/kg/min) on appetite and food intake in a randomised double-blind placebo-controlled crossover study in ten healthy volunteers. Infusion of PP reduced appetite and decreased the energy intake at a buffet lunch two hours post-infusion by 21.8 +/- 5.7% (P < 0.01). More importantly the inhibition of food intake was sustained, such that energy intake, as assessed by food diaries, was significantly reduced both the evening of the study and the following morning. Overall PP infusion reduced cumulative 24-hour energy intake by 25.3 +/- 5.8%. In conclusion our data demonstrates that PP causes a sustained decrease in both appetite and food intake.

Construction of a GP integration model.

There are frequent calls to improve integration of health services, within and between primary and secondary care sectors. In Australia, general medical practitioners (GPs) are central to these endeavours. This paper aims to better conceptualise GP integration and to develop a model and index based on this. A conceptualisation of integration is proposed based on integration fundamentally as an activity or process not structure. Integration process is the frequency and quality of episodes of information exchange involving the GP and another practitioner or patient and aimed at fulfilling the objectives of the health care system with regard to patient care. These are both direct responses to structural forces and emergent GP capacities and dispositions. The content of this typology was studied using Concept Mapping in 11 groups of GPs, consumers and other practitioners. Clusters of related statements within thematic domains were used as the basis for a provisional model. This was tested using confirmatory factor analysis in a data set derived from a national probability sample of 501 GPs. Some re-specification of the model was necessary, with three integration process factors needing to be subdivided. One factor congeneric model assumptions were used to identify the constituent items for these factors. The result was a model in which 50 items measured nine integration process factors and 20 items measured five enabling factors. Two distinct but correlated higher order factors, relating to individual patient care and public (or community) health--in contrast to a single higher order factor for integration--were identified. The re-specified model was tested with a new sample of 151 GPs and exhibited strong psychometric properties. Reliability and validity were acceptable to this stage of the indices' development. Further testing of the index is necessary to demonstrate factor invariance of the indices in other contexts as well as their utility in cross-structural analysis. That said, the indices have immediate uses.

Ghrelin causes hyperphagia and obesity in rats.

Ghrelin, a circulating growth hormone-releasing peptide derived from the stomach, stimulates food intake. The lowest systemically effective orexigenic dose of ghrelin was investigated and the resulting plasma ghrelin concentration was compared with that during fasting. The lowest dose of ghrelin that produced a significant stimulation of feeding after intraperitoneal injection was 1 nmol. The plasma ghrelin concentration after intraperitoneal injection of 1 nmol of ghrelin (2.83 +/- 0.13 pmol/ml at 60 min postinjection) was not significantly different from that occurring after a 24-h fast (2.79 +/- 0.32 pmol/ml). After microinjection into defined hypothalamic sites, ghrelin (30 pmol) stimulated food intake most markedly in the arcuate nucleus (Arc) (0-1 h food intake, 427 +/- 43% of control; P < 0.001 vs. control, P < 0.01 vs. all other nuclei), which is potentially accessible to the circulation. After chronic systemic or intracerebroventricular (ICV) administration of ghrelin for 7 days, cumulative food intake was increased (intraperitoneal ghrelin 13.6 +/- 3.4 g greater than saline-treated, P < 0.01; ICV ghrelin 19.6 +/- 5.5 g greater than saline-treated, P < 0.05). This was associated with excess weight gain (intraperitoneal ghrelin 21.7 +/- 1.4 g vs. saline 10.6 +/- 1.9 g, P < 0.001; ICV ghrelin 15.3 +/- 4.3 g vs. saline 2.2 +/- 3.8 g, P < 0.05) and adiposity. These data provide evidence that ghrelin is important in long-term control of food intake and body weight and that circulating ghrelin at fasting concentrations may stimulate food intake.