Leucine-enriched essential amino acid supplementation in mechanically ventilated trauma patients: a feasibility study.

BACKGROUND: Critically ill patients lose up to 2% of muscle mass per day. We assessed the feasibility of administering a leucine-enriched essential amino acid (L-EAA) supplement to mechanically ventilated trauma patients with the aim of assessing the effect on skeletal muscle mass and function. METHODS: A randomised feasibility study was performed over six months in intensive care (ICU). Patients received 5 g L-EAA five times per day in addition to standard feed (L-EAA group) or standard feed only (control group) for up to 14 days. C-reactive protein, albumin, IL-6, IL-10, urinary 3-MH, nitrogen balance, protein turnover ([1-13C] leucine infusion), muscle depth change (ultrasound), functional change (Katz and Barthel indices) and muscle strength Medical Research Council (MRC) sum score to assess ICU Acquired Weakness were measured sequentially. RESULTS: Eight patients (9.5% of screened patients) were recruited over six months. L-EAA doses were provided on 91/124 (73%) occasions. Inflammatory and urinary marker data were collected; serial muscle depth measurements were lacking due to short length of stay. Protein turnover studies were performed on five occasions. MRC sum score could not be performed as patients were not able to respond to the screening questions. The Katz and Barthel indices did not change. L-EAA delivery was achievable, but meaningful functional and muscle mass outcome measures require careful consideration in the design of a future randomised controlled trial. CONCLUSION: L-EAA was practical to provide, but we found significant barriers to recruitment and measurement of the chosen outcomes which would need to be addressed in the design of a future, large randomised controlled trial. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN79066838 . Registered on 25 July 2012.

Randomised clinical study: inulin short-chain fatty acid esters for targeted delivery of short-chain fatty acids to the human colon.

BACKGROUND: Short-chain fatty acids (SCFA) produced through fermentation of nondigestible carbohydrates by the gut microbiota are associated with positive metabolic effects. However, well-controlled trials are limited in humans. AIMS: To develop a methodology to deliver SCFA directly to the colon, and to optimise colonic propionate delivery in humans, to determine its role in appetite regulation and food intake. METHODS: Inulin SCFA esters were developed and tested as site-specific delivery vehicles for SCFA to the proximal colon. Inulin propionate esters containing 0-61 wt% (IPE-0-IPE-61) propionate were assessed in vitro using batch faecal fermentations. In a randomised, controlled, crossover study, with inulin as control, ad libitum food intake (kcal) was compared after 7 days on IPE-27 or IPE-54 (10 g/day all treatments). Propionate release was determined using (13) C-labelled IPE variants. RESULTS: In vitro, IPE-27-IPE-54 wt% propionate resulted in a sevenfold increase in propionate production compared with inulin (P < 0.05). In vivo, IPE-27 led to greater (13) C recovery in breath CO2 than IPE-54 (64.9 vs. 24.9%, P = 0.001). IPE-27 also led to a reduction in energy intake during the ad libitum test meal compared with both inulin (439.5 vs. 703.9 kcal, P = 0.025) and IPE-54 (439.5 vs. 659.3 kcal, P = 0.025), whereas IPE-54 was not significantly different from inulin control. CONCLUSIONS: IPE-27 significantly reduced food intake suggesting colonic propionate plays a role in appetite regulation. Inulin short-chain fatty acid esters provide a novel tool for probing the diet-gut microbiome-host metabolism axis in humans.

The effects of a diet rich in inulin or wheat fibre on markers of cardiovascular disease in overweight male subjects.

BACKGROUND: Previous studies suggest that the beneficial health effects of a diet rich in whole grains could be a result of the individual fibres found in the grain. The present study aimed to investigate the influence of a diet high in either wheat fibre (as an example of an insoluble fibre) or inulin (a nondigestible carbohydrate) on markers of cardiovascular disease. METHODS: Ten male participants classified as at higher risk of cardiovascular disease [mean (SD) body mass index 30.2 (3) kg m(-2) , mean (SD) waist circumference 106.4 (7) cm, mean (SD) age 39.8 (9) years] were recruited to a randomised, controlled, cross-over study comparing the consumption of bespoke bread rolls containing either inulin, wheat germ or refined grain (control) (15 g day(-1) ) for 4 weeks with a 4-week washout period between each regime. At the end of each regime, participants underwent an oral glucose tolerance test (OGTT), measures of pulse wave velocity (PWV), 24-h ambulatory blood pressure (AMBP), plasma lipid status and markers of glucose control. RESULTS: There was no difference in measures of glucose control, lipid status, 24-h AMBP or PWV after the intervention periods and no changes compared to baseline. There was no significant difference between OGTT glucose and insulin time profiles; however, there was a significant difference in area under the curves between the wheat fibre and control interventions when comparing change from baseline (control +10.2%, inulin +4.3%, wheat fibre -2.5%; P = 0.03). CONCLUSIONS: Only limited differences between the interventions were identified, perhaps as a consequence of the amount of fibre used and intervention length. The wheat germ intervention resulted in a significant reduction in glucose area under the curve, suggesting that this fibre may aid glucose control.

Influence of the tolerability of vinegar as an oral source of short-chain fatty acids on appetite control and food intake.

BACKGROUND: Vinegar is promoted as a natural appetite suppressant, based on previous reports that vinegar ingestion significantly increases subsequent satiety. However there are concerns about the appropriateness and safety of this advice, and it is unclear if poor product palatability may explain previously published effects on appetite. OBJECTIVE: To investigate if vinegar palatability and tolerability have a role in suppressing appetite and food intake in two sequential and related acute human feeding studies. SUBJECTS AND METHODS: Healthy, young, normal weight unrestrained eaters were recruited to Study 1 (n=16), an acute feeding study supplying vinegar within both palatable and unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar control; and to Study 2 (n=14), a modified sham feeding study (taste only without ingestion) comparing vinegar to a non-vinegar control following a milkshake preload. Both studies were a randomized crossover balanced design for the assessment of appetite, energy intake and glycaemic response. RESULTS: In Study 1, ingestion of vinegar significantly reduced quantitative and subjective measures of appetite, which were accompanied by significantly higher nausea ratings, with unpalatable treatment having the greatest effect. Significant correlations between palatability ratings and appetite measures were found. In Study 2, orosensory stimulation with vinegar did not influence subsequent subjective or quantitative measures of appetite compared with control. CONCLUSIONS: These studies indicate that vinegar ingestion enhances satiety whereas orosensory stimulation alone does not, and that these effects are largely due to poor tolerability following ingestion invoking feelings of nausea. On this basis the promotion of vinegar as a natural appetite suppressant does not seem appropriate.

Low glycaemic index diets and blood lipids: a systematic review and meta-analysis of randomised controlled trials.

AIMS: Low glycaemic index (GI) diets are beneficial in the management of hyperglycemia. Cardiovascular diseases are the major cause of mortality in diabetes therefore it is important to understand the effects of GI on blood lipids. The aim was to systematically review randomised controlled trials (RCTs) of low GI diets on blood lipids. DATA SYNTHESIS: We searched OVID Medline, Embase and Cochrane library to March 2012. Random effects meta-analyses were performed on twenty-eight RCTs comparing low- with high GI diets over at least 4 weeks (1272 participants; studies ranged from 6 to 155 participants); one was powered on blood lipids, 3 had adequate allocation concealment. Low GI diets significantly reduced total (-0.13 mmol/l, 95%CI -0.22 to -0.04, P = 0.004, 27 trials, 1441 participants, I(2) = 0%) and LDL-cholesterol (-0.16 mmol/l, 95%CI -0.24 to -0.08, P < 0.0001, 23 trials, 1281 participants, I(2) = 0%) compared with high GI diets and independently of weight loss. Subgroup analyses suggest that reductions in LDL-C are greatest in studies of shortest duration and greatest magnitude of GI reduction. Furthermore, lipid improvements appear greatest and most reliable when the low GI intervention is accompanied by an increase in dietary fibre. Sensitivity analyses, removing studies without adequate allocation concealment, lost statistical significance but retained suggested mean falls of ~0.10 mmol/l in both. There were no effects on HDL-cholesterol (MD -0.03 mmol/l, 95%CI -0.06 to 0.00, I(2) = 0%), or triglycerides (MD 0.01 mmol/l, 95%CI -0.06 to 0.08, I(2) = 0%). CONCLUSIONS: This meta-analysis provides consistent evidence that low GI diets reduce total and LDL-cholesterol and have no effect on HDL-cholesterol or triglycerides.

Effects of a novel propionate-rich sourdough bread on appetite and food intake.

BACKGROUND: There is evidence linking oral propionate to a reduction in food intake, which could confer functional food properties in the fight against obesity. However, propionate is typically volatile with a pungent smell and taste and so incorporating into foods naturally, at levels acceptable to the consumer is a novel approach. SUBJECTS/METHODS: Twenty healthy, young, normal weight unrestrained eaters underwent an acute feeding study using a palatable sourdough and an identical control bread of a similar palatability, in a randomized cross-over balanced design for the assessment of appetite and energy intake. RESULTS: No difference in energy intake of an ad libitum test meal, 180 min after the bread-based breakfast or in energy and macronutrient intake over the entire 24 h period was found between breads. Visual analogue scale ratings for appetite were not influenced by bread type, except the desire to eat something sweet. Elevated plasma insulin concentrations were observed following the propionate-rich sourdough breakfast (P=0.033 no effects of treatment on postprandial glycaemia were found. CONCLUSIONS: These findings suggest propionate-rich sourdough bread does not influence appetite and food intake unlike larger doses of the food preservative N-propionate.

A study of Hassawi rice (Oryza sativa L.) in terms of its carbohydrate hydrolysis (in vitro) and glycaemic and insulinaemic indices (in vivo).

BACKGROUND/OBJECTIVES: A high prevalence of Type 2 diabetes exists in Saudi Arabia. Epidemiological evidence suggests that low glycaemic index (GI) diets reduce diabetes risk. Yet, little is known about the GI of traditional Saudi Arabian staples such as Hassawi rice (HR). HR was evaluated in terms of its GI and insulinaemic index (II). Comparisons were made in vitro assessing glucose released enzymatically. A long-grain rice variety available in both United Kingdom and Saudi Arabia was studied as a comparison. SUBJECTS/METHODS: For GI and II measurements, HR, Uncle Ben's rice (UBR) and a standard glucose solution were consumed by healthy subjects (n=13) on seven randomised occasions. Capillary bloods were collected at specific times over 2 h after food intake. Food and Agriculture Organization/World Health Organization protocols were used to determine GI and II. For the in vitro studies, cooked rice was incubated with hydrolytic enzymes under standardised conditions. Samples were taken at t=20 and t=120 min and rapidly available glucose (RAG) and slowly available glucose (SAG) were computed. RESULTS: Values of RAG and SAG were lower for HR compared with their respective values for UBR (P<0.001 and P=0.011, respectively). However, no significant difference was observed for GI (P>0.05) despite a lower insulin response noted for HR (P=0.007). CONCLUSIONS: HR had a similar GI to UBR, although a lower insulin response was evident. RAG and SAG values were different for the two rice varieties despite similar GI values. These differences may be important in terms of their metabolic impact and outcome on diabetes.

Genetic predisposition influences plasma lipids of participants on habitual diet, but not the response to reductions in dietary intake of saturated fatty acids.

OBJECTIVE: SNPs identified from genome-wide association studies associate with lipid risk markers of cardiovascular disease. This study investigated whether these SNPs altered the plasma lipid response to diet in the 'RISCK' study cohort. METHODS: Participants (n=490) from a dietary intervention to lower saturated fat by replacement with carbohydrate or monounsaturated fat, were genotyped for 39 lipid-associated SNPs. The association of each individual SNP, and of the SNPs combined (using genetic predisposition scores), with plasma lipid concentrations was assessed at baseline, and on change in response to 24 weeks on diets. RESULTS: The associations between SNPs and lipid concentrations were directionally consistent with previous findings. The genetic predisposition scores were associated with higher baseline concentrations of plasma total (P=0.02) and LDL (P=0.002) cholesterol, triglycerides (P=0.001) and apolipoprotein B (P=0.004), and with lower baseline concentrations of HDL cholesterol (P<0.001) and apolipoprotein A-I (P<0.001). None of the SNPs showed significant association with the reduction of plasma lipids in response to the dietary interventions and there was no evidence of diet-gene interactions. CONCLUSION: Results from this exploratory study have shown that increased genetic predisposition was associated with an unfavourable plasma lipid profile at baseline, but did not influence the improvement in lipid profiles by the low-saturated-fat diets.

Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects.

BACKGROUND/OBJECTIVE: The sweet-taste receptor (T1r2+T1r3) is expressed by enteroendocrine L-cells throughout the gastrointestinal tract. Application of sucralose (a non-calorific, non-metabolisable sweetener) to L-cells in vitro stimulates glucagon-like peptide (GLP)-1 secretion, an effect that is inhibited with co-administration of a T1r2+T1r3 inhibitor. We conducted a randomised, single-blinded, crossover study in eight healthy subjects to investigate whether oral ingestion of sucralose could stimulate L-cell-derived GLP-1 and peptide YY (PYY) release in vivo. METHODS: Fasted subjects were studied on 4 study days in random order. Subjects consumed 50 ml of either water, sucralose (0.083% w/v), a non-sweet, glucose-polymer matched for sweetness with sucralose addition (50% w/v maltodextrin+0.083% sucralose) or a modified sham-feeding protocol (MSF=oral stimulation) of sucralose (0.083% w/v). Appetite ratings and plasma GLP-1, PYY, insulin and glucose were measured at regular time points for 120 min. At 120 min, energy intake at a buffet meal was measured. RESULTS: Sucralose ingestion did not increase plasma GLP-1 or PYY. MSF of sucralose did not elicit a cephalic phase response for insulin or GLP-1. Maltodextrin ingestion significantly increased insulin and glucose compared with water (P<0.001). Appetite ratings and energy intake were similar for all groups. CONCLUSIONS: At this dose, oral ingestion of sucralose does not increase plasma GLP-1 or PYY concentrations and hence, does not reduce appetite in healthy subjects. Oral stimulation with sucralose had no effect on GLP-1, insulin or appetite.

Resistant starch improves insulin sensitivity in metabolic syndrome.

AIMS: Diets rich in non-viscous fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. This study was undertaken to assess whether chronic consumption of this type of fibre in individuals with the metabolic syndrome would improve insulin sensitivity via changes in ectopic fat storage. METHODS: The study was a single-blind, randomized, parallel nutritional intervention where 20 insulin resistant subjects consumed either the fibre supplement (resistant starch) (40 g/day) or placebo supplement (0 g/day) for 12 weeks. Insulin sensitivity was measured by euglycaemic-hyperinsulinaemic clamp and ectopic fat storage measured by whole-body magnetic resonance spectroscopy. RESULTS: Resistant starch consumption did not significantly affect body weight, fat storage in muscle, liver or visceral depots. There was also no change with resistant starch feeding on vascular function or markers of inflammation. However, in subjects randomized to consume the resistant starch, insulin sensitivity improved compared with the placebo group (P = 0.023). Insulin sensitivity correlated significantly with changes in waist circumference and fat storage in tibialis muscle and to a lesser extent to visceral-to-subcutaneous abdominal adipose tissue ratio. CONCLUSION: Consumption of resistant starch improves insulin sensitivity in subjects with the metabolic syndrome. Unlike in animal models, diabetes prevention does not appear to be directly related to changes in body adiposity, blood lipids or inflammatory markers. Further research to elucidate the mechanisms behind this change in insulin sensitivity in human subjects is required.

Long-term cost-effectiveness of weight management in primary care.

BACKGROUND: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. METHODS: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. RESULTS: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was pound59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was pound2017 where background weight gain was limited to 0.5 kg/year, and pound2651 at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. CONCLUSION: Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

Inflammatory disease processes and interactions with nutrition.

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain omega-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (omega-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are required.

The effect of a 12-week low glycaemic index diet on heart disease risk factors and 24 h glycaemic response in healthy middle-aged volunteers at risk of heart disease: a pilot study.

OBJECTIVE: To compare the effects of two energy-restricted healthy diets, one with a low GI and one with a high GI, on heart disease risk factors and weight loss in subjects at risk of heart disease. DESIGN: A 12-week randomized parallel study of low and high GI, healthy eating diets was carried out. SETTING: The study was carried out at the Hammersmith Hospital. SUBJECTS: Eighteen subjects were recruited by advertisement and randomized to one of the two diets. Fourteen completed the study but one was excluded from the final analysis. METHODS: At randomization, subjects were advised to follow the intervention diet for 12 weeks. Before randomization and on completion of the study, anthropometrics, fasting cholesterol and glucose blood tests and 24-h glucose measurements were taken using a continuous glucose monitoring system (CGMS). Statistical analysis was carried out using non-parametric tests. Median (IQR) are presented. RESULTS: A significantly different dietary GI was achieved in the low GI (median: 51.3 (IQR: 51.0-52.0) compared to the high GI (59.3 (59.2-64.0) (P=0.032) group. By week 12, both groups reduced their energy intake by: low GI group: (-)167 ((-)312-(-)123) kcal/day (P=0018) vs high GI group: (-)596 ((-)625-(-)516) (P=0.018) kcal/day, the difference between the groups being significant (P=0.010). However, only the low GI group lost weight ((-)4.0 ((-)4.4-(-)2.4) kg (P=0.018) whereas the high GI group did not significantly change in weight ((-)1.5 ((-)3.6-0.8) kg (P=0.463). By week 12, the low GI group also had a significantly lower 24-h area under the curve (AUC) (7556 (7315-8434) vs 8841 (8424-8846) mmol-h/l (P=0.045) and overnight AUC (2429 (2423-2714) vs 3000 (2805-3072) mmol-h/l (P=0.006) glucose as measured by CGMS. There were no differences in the other heart disease risk factors assessed. CONCLUSIONS: This pilot study provides some evidence that consuming a low GI diet in addition to weight loss and healthy eating may reduce cardiovascular risk. Other potential benefits of GI might have been masked by weight loss in the low GI group. Larger-scale studies need to follow.

The Counterweight programme: Prevalence of CVD risk factors by body mass index and the impact of 10% weight change.

OBJECTIVES: To examine relationships between body mass index (BMI), prevalence of physician-recorded cardiovascular disease (CVD) risk factors in primary care, and changes in risk with 10% weight change. METHODS: The Counterweight Project conducted a baseline cross-sectional survey of medical records of 6150 obese (BMI ≥ 30 kg/m(2)), 1150 age- and sex-matched overweight (BMI 25 to <30 kg/m(2)), and 1150 age- and sex-matched normal weight (BMI 18.5 to <25 kg/m(2)) controls, in primary care. Data were collected for the previous 18 months to examine BMI and disease prevalence, and then modelled to show the potential effect of 10% weight loss or gain on risk. RESULTS: Obese patients develop more CVD risk factors than normal weight controls. BMI ≥ 40 kg/m(2) exhibits increased prevalence of type 2 diabetes mellitus (DM), odds ratio (OR) men: 6.16 (p < 0.001); women: 7.82 (p < 0.001) and hypertension OR men: 5.51 (p < 0.001); women: 4.16 (p < 0.001). Dyslipidaemia peaked around BMI 35 to <37.5 kg/m(2), OR men: 3.26 (p < 0.001); women 3.76 (p < 0.001) and CVD at BMI 37.5 to <40 kg/m(2) in men, OR 4.48 (p < 0.001) and BMI ≥ 40 kg/m(2) in women, OR 3.98 (p < 0.001). A 10% weight loss from the sample mean of 32.5 kg/m(2) reduced the OR for type 2 DM by 30% and CVD by 20%, while 10% weight gain increased type 2 DM risk by more than 35% and CVD by 20%. CONCLUSION: Obesity plays a fundamental role in CVD risk, which is reduced with weight loss. Weight management intervention strategies should be a public health priority to reduce the burden of disease in the population.

Low-dose oral tri-iodothyronine does not directly increase food intake in man.

Previously, we have shown that low-dose tri-iodothyronine (T3) increases food intake in rodents. This randomised, double-blind, placebo-controlled study aimed to investigate the effects of low-dose T3 on food intake in normal body weight individuals. However, despite an elevation in fT3 comparable to our earlier studies, administration of low-dose T3 in the fasted state did not stimulate food intake in man.

Glucagon-like peptide-1 (7-36) amide response to low versus high glycaemic index preloads in overweight subjects with and without type II diabetes mellitus.

BACKGROUND AND OBJECTIVE: Glucagon-like-peptide-1 (7-36) amide (GLP-1) is an insulin secretagogue and potential treatment for type II diabetes mellitus. An alternative to GLP-1 administration is endogenous dietary stimulation. We described a greater GLP-1 release following ingestion of liquids versus solids. We add to this work studying the effect of fluid preloads with differing glycaemic indices (GI) on the metabolic response to a meal. SUBJECTS AND DESIGN: GLP-1, insulin and glucose responses were measured in six overweight individuals and six subjects with type II diabetes on three occasions, after preload (milk, low GI; Ovaltine Light, high GI; or water, non-nutritive control) and meal ingestion. RESULTS: In people with and without diabetes, the high GI preload produced the greatest glucose incremental area under the curve (IAUC)(0-20), followed by the low GI preload, and water (P<0.001). In both groups, insulin IAUC(0-20) was higher following high and low GI preloads compared with water (NS). In people without diabetes, the GLP-1 response was higher when high and low GI preloads were consumed compared with water (P=0.041), with no significant difference between nutritive preloads. GLP-1 response did not differ between preloads in people with diabetes. Despite initial differences, total IAUCs(0-200) for biochemical variables did not differ by preload. CONCLUSION: We confirm that nutritive liquids stimulate GLP-1 to a greater extent than water in subjects without diabetes; however, this does not influence subsequent meal-induced response. The GI of preloads does not influence the degree of GLP-1 stimulation.

Failure of dietetic referral in patients with gastrointestinal cancer and weight loss.

This study examined whether staff working within a cancer centre treating patients with gastrointestinal malignancy routinely identified individuals from outpatients for referral to a dietitian. A nutrition screening tool is employed only for in-patient admissions. Height, current and usual weight were recorded prospectively in all patients referred for consideration of treatment. First appointment with the dietitian, first hospital admission, demographic and clinical details were obtained from hospital records. Time from first appointment to referral to a dietitian was examined. Between September 2002 and March 2004, 920 patients were included. Five hundred and seventeen patients had lost weight, of whom 223 patients had lost between 5% and 10% and 294 patients had lost more than 10% of their pre-morbid weight. Three hundred and twenty-seven patients (36%) were referred to dietitians. Twenty eight (9%) of referrals were made by staff in outpatients. Two hundred and ninety-nine were referred during or after an inpatient admission but only 39% of these occurred within the first seven days following admission. One third of patients with more than 10% weight loss were not referred for dietary assessment, even following admission. The likelihood of referral was significantly associated with the degree of weight loss (univariate analysis hazard ratio (HR) 1.75, 95% Confidence Interval (CI) 1.4-2.19, multivariate HR 1.65, 95% CI 1.22-2.23) and was independent of factors such as performance status and clinical setting. Few patients were identified early in their treatment for referral to a dietitian. Since most chemotherapy is now given on an outpatient basis, patients are unlikely to be referred if they do not require admission. This study suggests that an out-patient dietetic screening tool is urgently required. Such screening is likely to result in considerable improvements to the clinical care of cancer patients with weight loss.

Vulnerable patients with a fractured neck of femur: nutritional status and support in hospital.

BACKGROUND AND AIM: Malnutrition has serious consequences for recovery and increases the risk of complications in hospital patients. Fractured neck of femur (NOF) patients may be particularly at risk because of their old age and frail state of health. We conducted an observational study to evaluate the nutritional state and the nutritional support, which was provided to this group during their stay in hospital. METHODS: Twenty-five consecutive people admitted to an orthopaedic ward with a fractured NOF at Charing Cross Hospital, London were recruited. Anthropometric measures, biochemical indices, 3 days dietary intake and dietetic referral rates were collected. RESULTS: Patients had a significantly lower body mass index (BMI) compared with the mean BMI for sex and age in an elderly UK population (21.97 +/- 1.06 versus 26.73 +/- 0.03 kg m(-2); P < 0.005). They took just 58.6% of their energy requirements in hospital (4219 +/- 319 versus 7199 +/- 202 kJ mean(-1) daily intake over 3 days in week 2). Using the hospitals own nutritional risk assessment tool 56% of patients were found to be at risk of malnutrition on admission, which increased to 68% after 2-3 weeks. Of these 64% were referred to a dietitian and were given nutritional supplements. Nutritional assessment revealed that their nutritional status worsened during stay. CONCLUSIONS: This group of patients with fractured NOF is likely to be malnourished on admission and to show a rapid deterioration in its nutrition status during admission. Energy needs were not met in up to 50% of patients. These results reinforce the need to screen, supplement and monitor fractured NOF patients.

Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial.

BACKGROUND: Oxyntomodulin has recently been found to decrease body-weight in obese humans and may be a potential anti-obesity therapy. OBJECTIVE: To determine whether oxyntomodulin alters energy expenditure, in addition to reducing energy intake, in 'free-living' overweight and obese volunteers. DESIGN: Randomized double-blind controlled cross-over trial. SETTING: Community and hospital-based. PARTICIPANTS: Fifteen healthy overweight and obese men and women (age: 23-49 years, BMI: 25.1-39.0 kg/m(2)). All volunteers completed the study protocol. INTERVENTIONS: Four-day subcutaneous self-administration of pre-prandial oxyntomodulin, three times daily. Participants were advised to maintain their normal dietary and exercise regimen. MEASUREMENTS: (1) Energy expenditure, measured by indirect calorimetry and combined heart rate and movement monitoring; (2) energy intake, measured during a study meal. RESULTS: Oxyntomodulin administration reduced energy intake at the study meal by 128+/-29 kcal (P=0.0006) or 17.3+/-5.5% (P=0.0071), with no change in meal palatability. Oxyntomodulin did not alter resting energy expenditure; but increased activity-related energy expenditure by 143+/-109 kcal/day or 26.2+/-9.9% (P=0.0221); total energy expenditure by 9.4+/-4.8% (P=0.0454) and physical activity level by 9.5+/-4.6% (P=0.0495). A reduction in body weight of 0.5+/-0.2% was observed during the oxyntomodulin administration period (P=0.0232). CONCLUSION: Oxyntomodulin increases energy expenditure while reducing energy intake resulting in negative energy balance. This data supports the role of oxyntomodulin as a potential anti-obesity therapy.

Ghrelin stimulates insulin-induced glucose uptake in adipocytes.

The gastric and hypothalamic hormone ghrelin is the endogenous agonist of the growth hormone secretagogue receptor GHS-R1(a). Ghrelin stimulates growth hormone release and appetite via the hypothalamus. However, putative direct peripheral effects of ghrelin remain poorly understood. Rat adipose tissue expresses GHS-R1(a) mRNA, suggesting ghrelin may directly influence adipocyte function. We have investigated the effects of ghrelin on insulin-stimulated glucose uptake in isolated white adipocytes in vitro. RT-PCR confirmed the expression of GHS-R1(a) mRNA in epididymal adipose tissue. However, GHS-R1(a) expression was not detected in the peri-renal fat pads. Ghrelin increased insulin-stimulated deoxyglucose uptake in isolated white adipocytes extracted from the epididymal fat pads of male Wistar rats. Ghrelin 1000 nM significantly increased deoxyglucose uptake by 55% in the presence of 0.1 nM insulin. However, ghrelin administration in the absence of insulin had no effect on adipocyte deoxyglucose uptake, suggesting that ghrelin acts synergistically with insulin. Des-acyl ghrelin, a major circulating non-octanylated form of ghrelin, had no effect on insulin-stimulated glucose uptake. Furthermore, acylated ghrelin had no effect on deoxyglucose uptake in adipocytes from peri-renal fat pads suggesting that ghrelin may influence glucose uptake via the GHS-R1(a). Ghrelin therefore appears to directly potentiate adipocyte insulin-stimulated glucose uptake in selective adipocyte populations. Ghrelin may play a role in adipocyte regulation of glucose homeostasis.