Preliminary report: the effect of a 6-month dietary glycemic index manipulation in addition to healthy eating advice and weight loss on arterial compliance and 24-hour ambulatory blood pressure in men: a pilot study.

We aimed to determine whether altering dietary glycemic index (GI) in addition to healthy eating and weight loss advice affects arterial compliance and 24-hour blood pressure (BP), both coronary heart disease (CHD) risk factors. Middle-aged men with at least 1 CHD risk were randomized to a 6-month low-GI (LGI) or high-GI (HGI) diet. All were advised on healthy eating and weight loss. They were seen monthly to assess dietary compliance and anthropometrics. Carotid-femoral pulse wave velocity (PWV), fasting blood lipid profile, and glucose and insulin concentrations were measured at baseline and at months 3 and 6. Six-hour postprandial glucose and insulin responses and 24-hour ambulatory BP were also assessed at baseline and month 6. Thirty-eight subjects (HGI group, n = 16; LGI group, n = 22) completed the study. At month 6, groups differed in dietary GI, glycemic load, and carbohydrate intake (P < .001). Fasting insulin concentration and insulin resistance (calculated by homeostatic model assessment) were lower in the LGI than the HGI group (P < .01). The reduction in total cholesterol and 24-hour BP was bigger in the LGI than the HGI group (P < .05); and only the LGI group had significant reductions (P < .05) in PWV, low-density lipoprotein cholesterol, and triacylglycerol concentration. There were no differences in postprandial glucose or insulin responses between the groups. The results suggest that an LGI diet may be more beneficial in reducing CHD risk, including PWV and 24-hour BP, even in the setting of healthy eating and weight loss; and thus, further study is warranted.

The effect of dietary glycemic index on weight maintenance in overweight subjects: a pilot study.

Evidence suggests that a low-glycemic index (LGI) diet has a satiating effect and thus may enhance weight maintenance following weight loss. This study was conducted at Hammersmith Hospital, London, UK, and assessed the effect of altering diet GI on weight-loss maintenance. It consisted of a weight-loss phase and a 4-month randomized weight maintenance phase. Subjects were seen monthly to assess dietary compliance and anthropometrics. Appetite was assessed bimonthly by visual analogue scales while meal challenge postprandial insulin and glucose concentrations were assessed before and after the intervention. Following a median weight loss of 6.1 (interquartile range: 5.2-7.1) % body weight, subjects were randomized to a high-glycemic index (HGI) (n = 19) or LGI (n = 23) diet. Dietary composition differed only in GI (HGI group: 63.7 +/- 9.4; LGI group: 49.7 +/- 5.7, P < 0.001) and glycemic load (HGI group: 136.8 +/- 56.3; LGI group: 89.7 +/- 27.5, P < 0.001). Groups did not differ in body weight (weight change over 4 months, HGI group: 0.3 +/- 1.9 kg; LGI group: -0.7 +/- 2.9 kg, P = 0.3) or other anthropometric measurements. This pilot study suggests that in the setting of healthy eating, changing the diet GI does not appear to significantly affect weight maintenance.

Increased sucrose intake is not associated with a change in glucose or insulin sensitivity in people with type 2 diabetes.

BACKGROUND: Debate continues over the role of sucrose and sucrose-containing food in the diet for people with type 2 diabetes. Traditionally, dietary recommendations have suggested sucrose be reduced to a minimum level to improve glycaemic control. More recently the American Diabetes Association evidence-based guidelines have suggested a more liberal approach. OBJECTIVE: To investigate whether a 50 g increase in sucrose given as three slices of cake a day over a period of 24 days (88 +/- 7.5 g total sucrose/day) in combination with an increased monounsaturated fat intake (20% E) in line with current American Diabetes Association recommendations has an effect on glycaemic control or insulin sensitivity in people with type 2 diabetes. DESIGN: We re-examined results from a larger study that investigated the type of fat in the diet of people with type 2 diabetes. Nine overweight people with type 2 diabetes received a high-sucrose, high-monounsaturated-fat isocaloric diet for 24 days. Results Weight and glycaemic control remained stable throughout the study. There was no significant change in HbAlc over the study period. There was no change in insulin sensitivity, measured by the short insulin tolerance test. There was no change in fasting or postprandial incremental area under the curve in response to an identical standard test meal for glucose or insulin. CONCLUSIONS: Over the 3-week intervention period, an isocaloric increase in the dietary intakes of sucrose to 13% of total energy per day in people with type 2 diabetes was not associated with a decline in glycaemic control or insulin sensitivity.

Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery.

Meeting patients' nutritional requirements and preventing malnutrition is a challenge following major surgical procedures. The role of ghrelin in nutritional recovery after non-gastrointestinal major surgery is unknown. We used coronary artery bypass grafting (CABG) as an example of anticipated good recovery post major surgery.Seventeen patients undergoing CABG (mean +/- SEM: 70.1 +/- 2.2 yrs, BMI 29.1 +/- 1.4 kg/m2, 15 male) underwent fasting and postprandial (45 mins after standard test breakfast) blood sampling pre-operatively (day 0), post-operatively (day 6) and at follow-up (day 40). Changes in food intake, biochemical and anthropometric markers of nutritional status were recorded. A comparison was made to 17 matched healthy controls (70.6 +/- 2.3 yrs, BMI 28.4 +/- 1.3 kg/m2).We observed significantly increased post-operative and follow-up fasting ghrelin concentrations compared with pre-operatively (pre-op. 402 +/- 42 pmol/L vs post-op. 642 +/- 97 pmol/L vs follow-up 603 +/- 94 pmol/L) (ANOVA p < 0.05). Significantly exaggerated postprandial suppression of ghrelin was seen postoperatively and continued until follow-up (Delta pre-op. 10 +/- 51 pmol/L vs Delta post-op. -152 +/- 43 pmol/L vs Delta follow-up -159 +/- 65 pmol/L, p < 0.05). This was associated with a 50% reduction in food intake {post-op. 4.5 +/- 0.5 MJ/D (1076 +/- 120 kcal/D) compared with estimated requirements 9.9 +/- 0.5 MJ/D (2366 +/- 120 kcal/D)}, leading to a 4% weight loss and a 5% reduction in muscle arm circumference loss over length of follow up.Our data support the hypothesis that prolonged changes in fasting and postprandial plasma ghrelin concentrations are associated with impaired nutritional recovery after CABG. These findings reinforce the need to investigate ghrelin in other patients groups undergoing major surgery.

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.

Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease.

AIM: To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). METHODS: Whole body MRI and (1)H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). RESULTS: A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Significant correlations were found between decreases in IHCL and reductions in both intra-abdominal and abdominal subcutaneous AT. Improvements in liver function tests were associated with reductions in intra-abdominal AT, but not with changes in IHCL. CONCLUSION: This study shows that even a very modest reduction in body weight achieved through lifestyle modification can result in changes in body fat depots and improvements in LFTs.

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.

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.

Fasting and postprandial hyperghrelinemia in Prader-Willi syndrome is partially explained by hypoinsulinemia, and is not due to peptide YY3-36 deficiency or seen in hypothalamic obesity due to craniopharyngioma.

The cause of the unique elevation in fasting plasma levels of the orexigenic gastric hormone ghrelin in many patients with Prader-Willi syndrome (PWS) is unclear. We measured fasting and postprandial plasma ghrelin in nonobese (n = 16 fasting and n = 8 postprandial) and obese non-PWS adults (n = 16 and 9), adults with genetically confirmed PWS (n = 26 and 10), and patients with hypothalamic obesity from craniopharyngioma tumors (n = 9 and 6). We show that 1) plasma ghrelin levels decline normally after food consumption in PWS, but there is still fasting and postprandial hyperghrelinemia relative to the patient's obesity (2.0-fold higher fasting ghrelin, 1.8-fold higher postprandial ghrelin, adjusting for percentage of body fat); 2) the fasting and postprandial hyperghrelinemia in PWS appears to be at least partially, but possibly not solely, explained by the concurrent relative hypoinsulinemia and preserved insulin sensitivity for the patient's obesity (residual 1.3- to 1.6-fold higher fasting ghrelin, 1.2- to 1.5-fold higher postprandial ghrelin in PWS, adjusting for insulin levels or homeostasis model assessment of insulin resistance); 3) hyperghrelinemia and hypoinsulinemia are not found in craniopharyngioma patients with hypothalamic obesity, and indeed, these patients have relative hyperinsulinemia for their obesity; and 4) there is no deficiency of the anorexigenic intestinal hormone peptide YY(3-36) in PWS contributing to their hyperghrelinemia.

Elevated fasting plasma ghrelin in prader-willi syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance.

Plasma ghrelin is elevated in Prader-Willi syndrome (PWS). This might contribute to obesity or GH deficiency in such patients. Visceral adiposity and insulin resistance are reduced in PWS, which might lead to hyperghrelinemia. We measured fasting plasma ghrelin in control female (n = 39), PWS female (n = 12), and PWS male (n = 6) adults. In controls and PWS, ghrelin was negatively correlated with visceral adiposity, fasting insulin, and homeostasis model insulin resistance index. There was no significant correlation with serum IGF-I in PWS. In stepwise linear regression, visceral adiposity (P < 0.02) had a stronger inverse correlation with ghrelin than sc fat depots in controls and PWS, possibly through hyperinsulinemia, as the correlations with insulin resistance were even stronger (P < 0.01). PWS females had significantly (P < 0.001) elevated ghrelin (mean +/- SD, 661 +/- 360 pg/ml), compared with both nonobese (363 +/- 163) and obese (191 +/- 66) controls. Ghrelin was increased 3.4- to 3.6-fold in PWS females adjusting for total adiposity, 3.2- to 3.4-fold adjusting for visceral adiposity, and 3.0-fold adjusting for insulin resistance. Fasting plasma glucagon-like peptide-1 was normal in PWS females. The hyperghrelinemia in PWS adults is therefore not solely explained by their reduced visceral adiposity and relative hypoinsulinemia. Its cause and consequences await further elucidation.

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.

Gut hormone PYY(3-36) physiologically inhibits food intake.

Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY(3-36) (PYY(3-36)), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY(3-36) in rats inhibits food intake and reduces weight gain. PYY(3-36) also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY(3-36) increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY(3-36) inhibits food intake. PYY(3-36) also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY(3-36) significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY(3-36) may act through the arcuate nucleus Y2R to inhibit feeding in a gut-hypothalamic pathway.

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.

Resting metabolic rate, plasma leptin concentrations, leptin receptor expression, and adipose tissue measured by whole-body magnetic resonance imaging in women with Prader-Willi syndrome.

BACKGROUND: Obesity in Prader-Willi syndrome (PWS) may be related to abnormalities in the adipocyte-leptin-hypothalamic pathway and may be exacerbated by reductions in the resting metabolic rate (RMR). OBJECTIVE: We compared body composition, body-composition- adjusted RMR, and adiposity-adjusted plasma leptin between women with PWS and control women. We also examined leptin receptor expression in the PWS group. DESIGN: We studied body composition using whole-body magnetic resonance imaging and measured plasma leptin by radioimmunoassay in 45 control women aged 18-56 y and in 13 women with PWS aged 20-38 y. RMR was measured by indirect calorimetry in 41 control women and in 8 women with PWS. Age, body composition, and regional adipose tissue (AT) depots were corrected for by multiple regression analysis. Messenger RNA expression of the leptin receptor was examined by reverse transcriptase-polymerase chain reaction in lymphocytes. RESULTS: In the PWS group, fat mass was greater after correction for fat-free mass, and RMR was normal after correction for both fat-free mass and fat mass. Leptin was influenced primarily by subcutaneous AT volume in both subject groups. Leptin concentrations were not significantly different between the 2 groups after adjustment for age and AT content or distribution. Full-length leptin receptor messenger RNA was expressed in the lymphocytes of the PWS group. CONCLUSIONS: Differences in RMR in women with PWS are explained by abnormal body composition, suggesting that energy expenditure is normal at the tissue level in PWS. There is no evidence that defective leptin production causes obesity in PWS, and leptin receptor deficiency is not a primary consequence of the gene defects leading to leptin resistance.