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Biomedical subjects

Gary S Frost

Publications and source records attributed to Gary S Frost.

14 recordsLinked to original sources
PubMed2006

Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study.

INTRODUCTION: The nutritional status of patients in the intensive care unit (ICU) appears to decline not only during their stay in the ICU but also after discharge from the ICU. Recent evidence suggests that gut released peptides, such as ghrelin and peptide YY (PYY) regulate the initiation and termination of meals and could play a role in the altered eating behaviour of sick patients. The aim of this study was to assess the patterns of ghrelin and PYY levels during the stay of ICU patients in hospital. METHODS: Sixteen ICU patients (60 +/- 4.7 years, body mass index (BMI) 28.1 +/- 1.7 kg/m2 (mean +/- standard error of the mean)) underwent fasting blood sample collections on days 1, 3, 5, 14, 21 and 28 of their stay at Hammersmith and Charing Cross Hospitals. Changes in appetite and biochemical and anthropometric markers of nutritional status were recorded. A comparison was made to a group of 36 healthy volunteers matched for age and BMI (54.3 +/- 2.9 years, p = 0.3; BMI 25.8 +/- 0.8 kg/m2 p = 0.2). RESULTS: Compared to healthy subjects, ICU patients exhibited a significantly lower level of ghrelin (day one 297.8 +/- 76.3 versus 827.2 +/- 78.7 pmol/l, p < 0.001) during their stay in the ICU. This tended to rise to the normal level during the last three weeks of hospital stay. Conversely, ICU patients showed a significantly higher level of PYY (day one 31.5 +/- 9.6 versus 11.3 +/- 1.0 pmol/l, p < 0.05) throughout their stay in the ICU and on the ward, with a downward trend to the normal level during the last three weeks of stay. CONCLUSIONS: Results from our study show high levels of PYY and low levels of ghrelin in ICU patients compared to healthy controls. There appears to be a relationship between the level of these gut hormones and nutritional intake.

Adult↗
PubMed2005

Peptide YY3-36 and glucagon-like peptide-17-36 inhibit food intake additively.

Peptide YY (PYY) and glucagon like peptide (GLP)-1 are cosecreted from intestinal L cells, and plasma levels of both hormones rise after a meal. Peripheral administration of PYY(3-36) and GLP-1(7-36) inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral coadministration of PYY(3-36) with GLP-1(7-36) in rodents and man. Whereas high-dose PYY(3-36) (100 nmol/kg) and high-dose GLP-1(7-36) (100 nmol/kg) inhibited feeding individually, their combination led to significantly greater feeding inhibition. Additive inhibition of feeding was also observed in the genetic obese models, ob/ob and db/db mice. At low doses of PYY(3-36) (1 nmol/kg) and GLP-1(7-36) (10 nmol/kg), which alone had no effect on food intake, coadministration led to significant reduction in food intake. To investigate potential mechanisms, c-fos immunoreactivity was quantified in the hypothalamus and brain stem. In the hypothalamic arcuate nucleus, no changes were observed after low-dose PYY(3-36) or GLP-1(7-36) individually, but there were significantly more fos-positive neurons after coadministration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we coadministered PYY(3-36) and GLP-1(7-36) in man. Ten lean fasted volunteers received 120-min infusions of saline, GLP-1(7-36) (0.4 pmol/kg.min), PYY(3-36) (0.4 pmol/kg.min), and PYY(3-36) (0.4 pmol/kg.min) + GLP-1(7-36) (0.4 pmol/kg.min) on four separate days. Energy intake from a buffet meal after combined PYY(3-36) + GLP-1(7-36) treatment was reduced by 27% and was significantly lower than that after either treatment alone. Thus, PYY(3-36) and GLP-1(7-36), cosecreted after a meal, may inhibit food intake additively.

Animals↗
PubMed2005

Obesity impacts on general practice appointments.

OBJECTIVE: To quantify the impact of obesity on the number of visits to both primary and secondary care teams. RESEARCH METHODS AND PROCEDURES: The adult populations of 80 general practices throughout the United Kingdom were classified according to their BMI. We undertook a cross-sectional survey of computer-generated and handwritten records of 6150 obese people (BMI > or = 30 kg/m(2)) and 1150 normal weight (BMI = 18.5 to 24.9 kg/m(2)) control subjects over an 18-month retrospective period. RESULTS: Obese patients made significantly more visits to the general practitioner (GP), practice nurse (PN), and hospital outpatient units than normal weight patients (all p < 0.001), and they were admitted to the hospital more often (p = 0.034). For both GP and PN visits, the relationship remained after adjusting for age, sex, social deprivation category, country, and number of comorbidities. Among obese patients, there was an increasing relationship between frequent GP visits (at least four appointments) and greater BMI, which remained significant after adjustment had been made for age, sex, deprivation, country, and number of comorbidities. DISCUSSION: The human resource burden to general practice is significantly higher in the obese population than in the normal weight population, even when adjusted for confounding factors. The increase in prevalence of obesity will continue to put pressure on GP and PN time unless appropriate action is taken.

Adult↗
PubMed2005

The beneficial effect of a diet with low glycaemic index on 24 h glucose profiles in healthy young people as assessed by continuous glucose monitoring.

Elevated postprandial glycaemia has been linked to CVD in a number of different epidemiological studies involving predominantly non-diabetic volunteers. The MiniMed continuous glucose monitor, which measures blood glucose every 5 min, over a 24 h period, was used to investigate changes in blood glucose readings before and after instigating a diet with low glycaemic index (GI) for 1 week in free-living healthy individuals. Nine healthy people (age 27 (SEM 1.3) years, BMI 23.7 (SEM 0.7) kg/m2, one male, eight females) completed the study. A reduction in GI (59.7 (SEM 2) v. 52.1 (SEM 2), P<0.01) occurred in all nine subjects while energy and other macronutrients remained constant. A significant reduction was also observed in fasting glucose at 06.00 hours (5.4 (SEM 0.2) v. 4.4 (SEM 0.3) mmol/l, P<0.001), mean glucose (5.6 (SEM 0.2) v. 5.1 (SEM 0.2) mmol/l, P=0.004), area under the 24 h glucose curve (8102 (SEM 243) v. 750 (SEM 235) mmol/l per min, P=0.004) and area under the overnight, 8 h glucose curve (2677 (SEM 92) v. 2223 (SEM 121) mmol/l per min, P=0.01). The present study provides important data on how a simple adjustment to the diet can improve glucose profiles that, if sustained in the long term, would be predicted from epidemiological studies to have a favourable influence on CVD.

Adult↗
PubMed2005

Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial.

This study investigated the effect of subcutaneously administered oxyntomodulin on body weight in healthy overweight and obese volunteers. Participants self-administered saline or oxyntomodulin subcutaneously in a randomized, double-blind, parallel-group protocol. Injections were self-administered for 4 weeks, three times daily, 30 min before each meal. The volunteers were asked to maintain their regular diet and level of physical exercise during the study period. Subjects' body weight, energy intake, and levels of adipose hormones were assessed at the start and end of the study. Body weight was reduced by 2.3 +/- 0.4 kg in the treatment group over the study period compared with 0.5 +/- 0.5 kg in the control group (P = 0.0106). On average, the treatment group had an additional 0.45-kg weight loss per week. The treatment group demonstrated a reduction in leptin and an increase in adiponectin. Energy intake by the treatment group was significantly reduced by 170 +/- 37 kcal (25 +/- 5%) at the initial study meal (P = 0.0007) and by 250 +/- 63 kcal (35 +/- 9%) at the final study meal (P = 0.0023), with no change in subjective food palatability. Oxyntomodulin treatment resulted in weight loss and a change in the levels of adipose hormones consistent with a loss of adipose tissue. The anorectic effect was maintained over the 4-week period. Oxyntomodulin represents a potential therapy for obesity.

Adiponectin↗
PubMed2004

Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial.

There is a pressing need for more effective appetite-stimulatory therapies for many patient groups including those with cancer. We have previously demonstrated that the gastric hormone ghrelin potently enhances appetite in healthy volunteers. Here, we performed an acute, randomized, placebo-controlled, cross-over clinical trial to determine whether ghrelin stimulates appetite in cancer patients with anorexia. Seven cancer patients who reported loss of appetite were recruited from oncology clinics at Charing Cross Hospital. The main outcome measures were energy intake from a buffet meal during ghrelin or saline infusion and meal appreciation as assessed by visual analog scale. A marked increase in energy intake (31 +/- 7%; P = 0.005) was observed with ghrelin infusion compared with saline control, and every patient ate more. The meal appreciation score was greater by 28 +/- 8% (P = 0.02) with ghrelin treatment. No side effects were observed. The stimulatory effects of ghrelin on food intake and meal appreciation seen in this preliminary study suggest that ghrelin could be an effective treatment for cancer anorexia and possibly for appetite loss in other patient groups.

Adult↗
PubMed2003

Inhibition of food intake in obese subjects by peptide YY3-36.

BACKGROUND: The gut hormone fragment peptide YY3-36 (PYY) reduces appetite and food intake when infused into subjects of normal weight. In common with the adipocyte hormone leptin, PYY reduces food intake by modulating appetite circuits in the hypothalamus. However, in obesity there is a marked resistance to the action of leptin, which greatly limits its therapeutic effectiveness. We investigated whether obese subjects were also resistant to the anorectic effects of PYY. METHODS: We compared the effects of PYY infusion on appetite and food intake in 12 obese and 12 lean subjects in a double-blind, placebo-controlled, crossover study. The plasma levels of PYY, ghrelin, leptin, and insulin were also determined. RESULTS: Caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in the obese subjects (P<0.001) and 31 percent in the lean subjects (P<0.001). PYY infusion also caused a significant decrease in the cumulative 24-hour caloric intake in both obese and lean subjects. PYY infusion reduced plasma levels of the appetite-stimulatory hormone ghrelin. Endogenous fasting and postprandial levels of PYY were significantly lower in obese subjects (the mean [+/-SE] fasting PYY levels were 10.2+/-0.7 pmol per liter in the obese group and 16.9+/-0.8 pmol per liter in the lean group, P<0.001). Furthermore, the fasting PYY levels correlated negatively with the body-mass index (r = -0.84, P<0.001). CONCLUSIONS: We found that obese subjects were not resistant to the anorectic effects of PYY. Endogenous PYY levels were low in the obese subjects, suggesting that PYY deficiency may contribute to the pathogenesis of obesity.

Appetite↗
PubMed2003

A randomised four-intervention crossover study investigating the effect of carbohydrates on daytime profiles of insulin, glucose, non-esterified fatty acids and triacylglycerols in middle-aged men.

Postprandial concentrations of glucose, insulin and triacylglycerols (TG) correlate to risk for CHD. Carbohydrates affect many metabolites that could have a potential effect on cardiovascular risk factors. The objective of the present study was to examine, using a randomised prospective study, the acute (day 1) and ad libitum medium-term (day 24) effects of four diets: a high-fat diet (HIGH-FAT; 50 % fat, >34 % monounsaturated fatty acids); a low-glycaemic index (GI) diet (LOW-GI; high-carbohydrate, low-GI); a high-sucrose diet (SUCROSE; high carbohydrate increase of 90 g sucrose/d); a high-GI diet (HIGH-GI; high-carbohydrate, high-GI). Daytime profiles (8 h) (breakfast, lunch and tea) of lipid and carbohydrate metabolism were completed during day 1 and day 24. Seventeen middle-aged men with one or more cardiac risk factors completed the study. There was no change from day 1 or between diets in fasting glucose, lipids or homeostatic assessment model (HOMA) on day 24. The HIGH-FAT compared with the three high-carbohydrate diets was associated with lower postprandial insulin and glucose but higher postprandial TG and non-esterified fatty acids (NEFA). There was a significant increase in the 6 h (15.00 hours) TG concentration (day 1, 2.6 (sem 0.3) mmol/l v. day 24, 3.3 (sem 0.3) mmol/l; P<0.01) on the SUCROSE diet. Postprandial HOMA (i.e. incremental area under the curve (IAUC) glucose (mmol/l per min)xIAUC insulin/22.5 (mU/l per min)) median changes from day 1 to day 24 were -61, -43, -20 and +31 % for the HIGH-FAT, LOW-GI, SUCROSE and HIGH-GI diets respectively. The HIGH-GI percentage change was significantly different from the other three diets (P<0.001). Despite being advised to maintain an identical energy intake there was a significant weight change (-0.27 (sem 0.3) kg; P<0.02) on the LOW-GI diet compared with the SUCROSE diet (+0.84 (sem 0.3) kg). In conclusion the HIGH-FAT diet had a beneficial effect on postprandial glucose and insulin over time but it was associated with higher postprandial concentrations of TG and NEFA. Conversely the HIGH-GI diet appeared to increase postprandial insulin resistance over the study period.

Area Under Curve↗
PubMed2003

Carbohydrate-induced manipulation of insulin sensitivity independently of intramyocellular lipids.

Subjects with insulin resistance have been shown to have higher storage levels of intramyocellular lipid (IMCL) than their insulin-sensitive counterparts. It has been proposed that elevated IMCL stores may be the main cause of insulin resistance. The aim of the present study was to ascertain whether there is a causal relationship between IMCL storage and insulin resistance. IMCL storage was assessed using magnetic resonance spectroscopy and insulin sensitivity was assessed by performing an oral glucose tolerance test. A 4-week intervention of reduction of dietary glycaemic index was used to manipulate insulin sensitivity in a cohort of healthy volunteers; the effects of this intervention on IMCL were measured after 4 weeks of intervention. Significant improvements in the insulin sensitivity index occurred following the dietary intervention (baseline 7.8 (sem 1.11) v. post-intervention 9.7 (sem 1.11), P=0.02). However, there were no changes in IMCL storage levels, suggesting that insulin sensitivity can be manipulated independently of IMCL. This suggests that in healthy volunteers, insulin sensitivity is independent of IMCL storage and the high storage levels that have been found in insulin-resistant subjects may occur as a consequence rather than a cause of insulin resistance.

Adult↗
PubMed2003

Oxyntomodulin suppresses appetite and reduces food intake in humans.

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.

Adult↗
PubMed2002

Treating obesity: a follow-up study. Can the stages of change model be used as a postal screening tool?

AIMS: We have previously shown that although a postal questionnaire based on the stages of change model (SCQ) failed to distinguish outpatients most likely to lose weight, it appeared to influence attendance rates. We therefore audited attendance upon receiving a pre-appointment SCQ in the post and compared this to previous standard practice in 1996. METHODOLOGY AND RESULTS: Seventy-eight obese outpatients (BMI 36.7 +/- 6.7 kg m-2, age 43 +/- 15 years) (mean +/- SD) were included. Twenty-nine per cent of patients failed to return an SCQ and were not sent an appointment and therefore did not block dietetic time. Eleven per cent returned an SCQ but did not attend (DNA) visit 1, whilst 21% attended visit 1 but DNA visit 2. Thirty-nine per cent attended both appointments and lost a significant amount of weight (105 +/- 23 vs. 103.2 +/- 23 kg, P < 0.0001) in 4 weeks. There was no difference in SCQ results between groups. Overall attendance rate at initial and follow-up appointments increased by 11%, while DNA rates fell by 20% compared with the 1996 audit. CONCLUSION: The SCQ has sifted out one in four patients who previously DNA an initial dietetic outpatient appointment. This has reduced waiting-list time as appointments are only book on return on the SCQ form, increased effective use of dietetic time through increased attendance rates, and lowered the DNA rate of follow-up appointments.

Adolescent↗
PubMed2002

Men at increased risk of coronary heart disease are not different from age- and weight-matched healthy controls in their postprandial triglyceride, nonesterified fatty acid, or incretin responses to sucrose.

Short-term studies suggest that extreme sucrose consumption has a detrimental effect on triglycerides (TG) in hypertriglyceridemic people. There is currently no consensus on the short-term inclusion of a moderate intake of sucrose in middle-aged men at increased risk of coronary heart disease (CHD). It is also unknown whether gut hormones that are released in response to carbohydrate ingestion modulate any of the effects of sucrose. The aim of this study was to further elucidate whether men at increased risk of CHD have an exaggerated response to sucrose compared with age- and weight-matched controls over an acute postprandial period. Twenty middle-aged men were recruited and separated into control (total cholesterol < 5.5 mmol/L) and increased risk of CHD (> 5.5 mmol/L) groups. We measured postprandial TG, nonesterified fatty acids (NEFA), insulin, glucose, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations in response to a meal containing 75 g glucose or 75 g sucrose with a moderate fat load. The increased risk group had significantly higher Framingham risk assessment (12% v 4%), TG (2.4 +/- 1.5 v 1.1 +/- 0.4 mmol/L), low-density lipoprotein-cholesterol (LDL-C) (4.4 +/- 0.5 v 2.7 +/- 0.4 mmol/L), and lower high-density lipoprotein-cholesterol (HDL-C) (1.2 +/- 0.2 v 1.5 +/- 0.2 mmol/L) (P <.05 for all). There was no significant difference in the incremental area under the curve (IAUC, 0 to 360 minutes) for TG, NEFA, glucose, GLP-1, or GIP in response to glucose or sucrose within or between the groups. Absolute total area under the curve (not IAUC) for TG was significantly higher in the increased risk group for both glucose and sucrose, respectively (P =.01). A total of 75 g of sucrose given as part of a single meal appears to make little difference in the postprandial TG and NEFA response in men with or without risk of CHD compared with glucose. Although long-term data is needed, this begs the question whether a moderate intake of sucrose has been overemphasized as a detrimental dietary message in middle-aged men.

Blood Glucose↗
PubMedDate not supplied

Peptide YY (PYY) is increased in elderly patients with femoral neck fractures: a prospective cohort study.

BACKGROUND: Peptide YY (PYY), a gut peptide, has recently been shown to inhibit appetite. The role of this peptide in elderly nutritionally-compromised patients with femoral neck fracture (FNF) has not been investigated. In this study, we investigated the longitudinal pattern of PYY levels during hospital stay and investigated the postprandial PYY response to a standard meal in patients with FNF and matched controls. METHODS: Fasting plasma concentrations of the PYY were measured on days 1, 4, 7, 14, 21 and 28 or on discharge from the hospital in 17 white patients with FNF. On the second week of stay, 13 patients with FNF consumed a standard breakfast following an overnight fasting. One fasting sample and one 45-minute postmeal sample were collected. A control group was made up of 17 matched healthy elderly patients. RESULTS: PYY concentrations were increased significantly over the length of hospital stay. Results of the test breakfast suggested a significant and exaggerated post-prandial PYY response, despite a smaller energy intake being consumed. CONCLUSIONS: This study shows PYY concentrations are increased during hospitalization and their post-prandial release exaggerated in this group of vulnerable patients, and suggests a role in the etiology of reduced appetite in this patient group.

Aged, 80 and over↗