Impact of restraint and disinhibition on PYY plasma levels and subjective feelings of appetite.

The impact of eating behaviours on circulating levels of appetite-regulating hormones remains largely unknown. The aims of this study were to assess the role of restraint and disinhibition on fasting/postprandial peptide YY (PYY) plasma levels and subjective feelings of appetite in normal-weight individuals and to determine whether the effect was energy load dependent. 33 participants (12 men) were classified as restrained/unrestrained and low/high in disinhibition based on Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint/disinhibition on PYY plasma levels and feelings of appetite was measured, after a 500kcal and 1000kcal breakfast, using a randomised crossover design. Restraint did not impact on either fasting or postprandial PYY plasma levels, but participants with high disinhibition had a tendency towards a blunted postprandial PYY response. Moreover, restrained eaters reported lower ratings of prospective food consumption postprandially, and a tendency towards higher fullness/lower hunger. In conclusion, circulating PYY is unaffected by restrained eating behaviour, despite being associated with increased fullness and reduced hunger in the fed state. High levels of disinhibition tend to be associated with a blunted PYY response and this may contribute towards the susceptibility to overconsumption and increased risk of weight gain characteristic of this trait.

Effects of restrained eating behaviour on insulin sensitivity in normal-weight individuals.

Restrained eating behaviour has been linked to abnormalities in metabolic and endocrine functions. However, the impact of restraint on fasting insulin and glucose plasma levels and insulin sensitivity remains controversial. Moreover, the few postprandial studies to date are limited by an inappropriate sampling time frame and a low "net" energy and carbohydrate load. The aims of this study are to assess the role of dietary restraint on fasting and postprandial plasma levels of insulin, glucose, triacylglycerol (TAG) and non esterified fatty acids (NEFA) in healthy volunteers with a normal and stable body weight and to determine whether the effect of restraint on the plasma levels of the previous hormones/metabolites is load dependent. Normal-weight participants (21 women and 12 men) were classified as restrained/unrestrained based on the restraint scale of the Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint on the plasma levels of different hormones/metabolites was measured, in response to a 500 kcal and 1000 kcal breakfast, using a randomised crossover design. Restraint was associated with lower fasting insulin plasma levels (P<0.05) and a lower insulin (P<0.015) and glucose (P<0.05) plasma levels in the postprandial state, but did not impact on TAG or NEFA. Moreover, restrained eaters showed a better fasting (P<0.05) and postprandial insulin sensitivity (P<0.01). Restrained eating behaviour has, therefore, a significant impact on both fasting and postprandial glucose metabolism, being associated with increased insulin sensitivity. These findings suggest the need for adjusting for restraint level in studies where glucose metabolism is a major outcome.

Comparison of the effects of four commercially available weight-loss programmes on lipid-based cardiovascular risk factors.

OBJECTIVE: To investigate the relative efficacy of four popular weight-loss programmes on plasma lipids and lipoproteins as measures of CVD risk. DESIGN: A multi-centred, randomised, controlled trial of four diets - Dr Atkins' New Diet Revolution, The Slim-Fast Plan, Weight Watchers Pure Points programme and Rosemary Conley's 'Eat yourself Slim' Diet and Fitness Plan - against a control diet, in parallel for 6 months. SETTING AND SUBJECTS: The trial was conducted at five universities across the UK (Surrey, Nottingham, Ulster (Coleraine), Bristol and Edinburgh (Queen Margaret University College)) and involved the participation of 300 overweight and obese males and females aged 21-60 years in a community setting. RESULTS: Significant weight loss was achieved by all dieting groups (5-9 kg at 6 months) but no significant difference was observed between diets at 6 months. The Weight Watchers and Rosemary Conley (low-fat) diets were followed by significant reductions in plasma LDL cholesterol (both -12.2 % after 6 months, P < 0.01), whereas the Atkins (low-carbohydrate) and Weight Watchers diets were followed by marked reductions in plasma TAG (-38.2 % and -22.6 % at 6 months respectively, P < 0.01). These latter two diets were associated with an increase in LDL particle size, a change that has been linked to reduced CVD risk. CONCLUSIONS: Overall, these results demonstrate the favourable effects of weight loss on lipid-mediated CVD risk factors that can be achieved through commercially available weight-loss programmes. No detrimental effects on lipid-based CVD risk factors were observed in participants consuming a low-carbohydrate diet.

Postprandial metabolic profiles following meals and snacks eaten during simulated night and day shift work.

Shift workers are known to have an increased risk of developing cardiovascular disease (CVD) compared with day workers. An important factor contributing to this increased risk could be the increased incidence of postprandial metabolic risk factors for CVD among shift workers, as a consequence of the maladaptation of endogenous circadian rhythms to abrupt changes in shift times. We have previously shown that both simulated and real shift workers showed relatively impaired glucose and lipid tolerance if a single test meal was consumed between 00:00-02:00 h (night shift) compared with 12:00-14:00 h (day shift). The objective of the present study was to extend these observations to compare the cumulative metabolic effect of consecutive snacks/meals, as might normally be consumed throughout a period of night or day shift work. In a randomized crossover study, eight healthy nonobese men (20-33 yrs, BMI 20-25kg/m2) consumed a combination of two meals and a snack on two occasions following a standardized prestudy meal, simulating night and day shift working (total energy 2500 kcal: 40% fat, 50% carbohydrate, 10% protein). Meals were consumed at 01:00/ 13:00 h and 07:00/19:00h, and the snack at 04:00/16:00 h. Blood was taken after an overnight fast, and for 8 h following the first meal on each occasion, for the measurement of glucose, insulin, triacylglycerol (TAG), and nonesterified fatty acids (NEFA). RM-ANOVA (factors time and shift) showed a significant effect of shift for plasma TAG, with higher levels on simulated night compared to day shift (p < 0.05). There was a trend toward an effect of shift for plasma glucose, with higher plasma glucose at night (p = 0.08), and there was a time-shift interaction for plasma insulin levels (p < 0.01). NEFA levels were unaffected by shift. Inspection of the area under the plasma response curve (AUC) following each meal and snack revealed that the differences in lipid tolerance occurred throughout the study, with greatest differences occurring following the mid-shift snack. In contrast, glucose tolerance was relatively impaired following the first night-time meal, with no differences observed following the second meal. Plasma insulin levels were significantly lower following the first meal (p < 0.05), but significantly higher following the second meal (p < 0.01) on the simulated night shift. These findings confirm our previous observations of raised postprandial TAG and glucose at night, and show that sequential meal ingestion has a more pronounced effect on subsequent lipid than carbohydrate tolerance.

Physiological mechanisms mediating aspartame-induced satiety.

Aspartame has been previously shown to increase satiety. This study aimed to investigate a possible role for the satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in this effect. The effects of the constituents of aspartame, phenylalanine and aspartic acid, were also examined. Six subjects consumed an encapsulated preload consisting of either 400 mg aspartame, 176 mg aspartic acid+224 mg phenylalanine, or 400 mg corn flour (control), with 1.5 g paracetamol dissolved in 450 ml water to measure gastric emptying. A 1983-kJ liquid meal was consumed 60 min later. Plasma CCK, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, and insulin were measured over 0-120 min. Gastric emptying was measured from 0 to 60 min. Plasma GLP-1 concentrations decreased following the liquid meal (60-120 min) after both the aspartame and amino acids preloads (control, 2096.9 pmol/l min; aspartame, 536.6 pmol/l min; amino acids, 861.8 pmol/l min; incremental area under the curve [AUC] 60-120 min, P<.05). Desire to eat was reduced from 60 to 120 min following the amino acids preload (control, -337.1 mm min; aspartame, -505.4 mm min; amino acids, -1497.1 mm min; incremental AUC 60-120 min, P<.05). However, gastric emptying rates, plasma CCK, GIP, insulin, and glucose concentrations were unaffected. There was a correlation between the increase in plasma phenylalanine and decrease in desire to eat after the liquid meal following the constituent amino acids (r=-.9774, P=.004). In conclusion, it is unlikely that aspartame increases satiety via CCK- or GLP-1-mediated mechanisms, but small changes in circulating phenylalanine concentrations may influence appetite.

Glucose-dependent insulinotropic polypeptide and insulin-like immunoreactivity in saliva following sham-fed and swallowed meals.

Gastrointestinal peptides, including insulin, glucagon and glucose-dependent insulinotropic polypeptide (GIP) have previously been reported in salivary glands. Recent evidence has suggested they might influence postprandial macronutrient metabolism. This study therefore investigated and compared postprandial hormone concentrations in saliva and plasma to determine whether their secretion was influenced by oral food stimuli. In a within-subject randomised cross-over comparison of hormone concentrations in plasma and saliva following a mixed meal, 12 subjects were given two 1708 kJ mixed meals. On one occasion the meal was chewed and swallowed (swallowed meal), on the other it was chewed and expectorated (sham-fed meal). Salivary and plasma levels of immunoreactive insulin, GIP and glucagon-like peptide-1 (GLP-1), total protein, alpha-amylase, glucose and non-esterified fatty acid were measured before and for 90 min following the meals. Saliva total protein and alpha-amylase rose following both meals, indicating that the stimulus for salivary protein release is related to the presence of food in the mouth. GLP-1 was not detected in saliva. Fasting salivary insulin levels were lower in saliva than plasma (28+/-6 vs 40+/-25 pmol/l respectively). Both increased following the swallowed meal but the rise in saliva was slower and less marked than in plasma (peak levels 96+/-18 and 270+/-66 pmol/l for saliva and plasma respectively, P<0.01). Both were unchanged following the sham-fed meal. GIP was detected in saliva. Fasting GIP levels were significantly higher in saliva than plasma (183+/-23 compared with 20+/-7 pmol/l, P<0.01). They decreased in saliva following both swallowed and sham-fed meals to nadirs of 117+/-17 and 71+/-12 pmol/l respectively, but rose following the swallowed meal to peak levels of 268+/-66 pmol/l. These findings are consistent with insulin in saliva being an ultrafiltrate of that circulating in blood, but GIP in saliva being the product of local salivary gland synthesis, whose secretion is influenced, directly or indirectly, by oral stimuli. The function of salivary GIP is unknown, but we speculate that it may play a role in the regulation of gastric acid secretion in the fasting state.

Prior short-term consumption of resistant starch enhances postprandial insulin sensitivity in healthy subjects.

AIMS/HYPOTHESIS: Diets rich in insoluble-fibre are linked to a reduced risk of both diabetes and cardiovascular disease; however, the mechanism of action remains unclear. The aim of this study was to assess whether acute changes in the insoluble-fibre (resistant starch) content of the diet would have effects on postprandial carbohydrate and lipid handling. METHODS: Ten healthy subjects consumed two identical, low-residue diets on separate occasions for 24 h (33% fat; <2 g dietary fibre). Of the diets one was supplemented with 60 g resistant starch (Novelose 260). On the following morning a fibre-free meal tolerance test (MTT) was carried out (59 g carbohydrate; 21 g fat; 2.1 kJ) and postprandial insulin sensitivity (SI(ORAL)) assessed using a minimal model approach. RESULTS: Prior resistant starch consumption led to lower postprandial plasma glucose (p=0.037) and insulin (p=0.038) with a higher insulin sensitivity(44+/-7.5 vs 26+/-3.5 x 10(-4) dl kg(-1) min(-1) per micro Uml(-1); p=0.028) and C-peptide-to-insulin molar ratio (18.7+/-6.5 vs 9.7+/-0.69; p=0.017). There was no effect of resistant starch consumption on plasma triacylglycerol although non-esterified fatty acid and 3-hydroxybutyrate levels were suppressed 5 h after the meal tolerance test. CONCLUSION: Prior acute consumption of a high-dose of resistant starch enhanced carbohydrate handling in the postprandial period the following day potentially due to the increased rate of colonic fermentation.

Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite.

Protein, generally agreed to be the most satiating macronutrient, may differ in its effects on appetite depending on the protein source and variation in digestion and absorption. We investigated the effects of two milk protein types, casein and whey, on food intake and subjective ratings of hunger and fullness, and on postprandial metabolite and gastrointestinal hormone responses. Two studies were undertaken. The first study showed that energy intake from a buffet meal ad libitum was significantly less 90 min after a 1700 kJ liquid preload containing 48 g whey, compared with an equivalent casein preload (P<0.05). In the second study, the same whey preload led to a 28 % increase in postprandial plasma amino acid concentrations over 3 h compared with casein (incremental area under the curve (iAUC), P<0.05). Plasma cholecystokinin (CCK) was increased by 60 % (iAUC, P<0.005), glucagon-like peptide (GLP)-1 by 65 % (iAUC, P<0.05) and glucose-dependent insulinotropic polypeptide by 36 % (iAUC, P<0.01) following the whey preload compared with the casein. Gastric emptying was influenced by protein type as evidenced by differing plasma paracetamol profiles with the two preloads. Greater subjective satiety followed the whey test meal (P<0.05). These results implicate post-absorptive increases in plasma amino acids together with both CCK and GLP-1 as potential mediators of the increased satiety response to whey and emphasise the importance of considering the impact of protein type on the appetite response to a mixed meal.

The ability of habitual exercise to influence appetite and food intake in response to high- and low-energy preloads in man.

The present study tested the hypothesis that habitual exercisers demonstrate an increased accuracy of regulation of food intake in compensation for previous dietary energy intake. Twenty-three lean healthy male subjects were divided into two groups on the basis of their habitual exercise levels: non-exercisers (no exercise sessions/week, n 9), and exercisers (>two exercise sessions of 40 min or more/week, n 14). The appetite response to covert liquid preloads of high (2513 kJ) energy (HE) and low (1008 kJ) energy (LE) was investigated Sixty minutes after the preload subjects were offered an ab libitum buffet-style meal and energy intake (EI) was calculated. Subjective hunger and satiety were assessed throughout using self-rated visual-analogue scales. Buffet EI in non-exercisers was not significantly different following the LE or HE preloads (mean compensation 7 %), but the exercise group significantly reduced their energy intake following the HE, compared with the LE, preload (mean compensation 90 %; P=0.0035). A broadly similar pattern of response was observed for both moderate (two to three sessions/week, n 7) and high exercisers (>four sessions/week, n 7). There were no significant differences between hunger or satiety ratings following HE or LE preloads for either group. However non-exercisers scored significantly higher on their self-ratings of hunger at the start of the study, before preload consumption, compared with the exercisers (P<0.01). These findings demonstrate that habitual exercisers have an increased accuracy of short-term regulation of food intake in compensation for preload manipulation, and provide additional support for advocating regular exercise in the prevention of overweight and obesity.

Postprandial hormone and metabolic responses amongst shift workers in Antarctica.

The circadian rhythms of many night-shift workers are maladapted to their imposed behavioural schedule, and this factor may be implicated in the increased occurrence of cardiovascular disease (CVD) reported in shift workers. One way in which CVD risk could be mediated is through inappropriate hormonal and metabolic responses to meals. This study investigated the responses to standard meals at different circadian times in a group of night-shift workers on a British Antarctic Survey station at Halley Bay (75 degrees S) in Antarctica. Twelve healthy subjects (ten men and two women) were recruited. Their postprandial hormone and metabolic responses to an identical mixed test meal of 3330 kJ were measured on three occasions: (i) during daytime on a normal working day, (ii) during night-time at the beginning of a period of night-shift work, and (iii) during the daytime on return from night working to daytime working. Venous blood was taken for 9 h after the meal for the measurement of glucose, insulin, triacylglycerol (TAG) and non-esterified fatty acids. Urine was collected 4-hourly (longer during sleep) on each test day for assessment of the circadian phase via 6-sulphatoxymelatonin (aMT6s) assay. During normal daytime working, aMT6s acrophase was delayed (7.7+/-1.0 h (s.e.m.)) compared with that previously found in temperate zones in a comparable age-group. During the night shift a further delay was evident (11.8+/-1.9 h) and subjects' acrophases remained delayed 2 days after return to daytime working (12.4+/-1.8 h). Integrated postprandial glucose, insulin and TAG responses were significantly elevated during the night shift compared with normal daytime working. Two days after their return to daytime working, subjects' postprandial glucose and insulin responses had returned to pre-shift levels; however, integrated TAG levels remained significantly elevated. These results are very similar to those previously found in simulated night-shift conditions; it is the first time such changes have been reported in real shift workers in field conditions. They provide evidence that the abnormal metabolic responses to meals taken at night during unadapted night shifts are due, at least in part, to a relative insulin resistance, which could contribute to the documented cardiovascular morbidity associated with shift work. When applied to the 20% of the UK workforce currently employed on shift work, these findings have major significance from an occupational health perspective.

A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans.

Seven studies have now been published pertaining to the acute effect of iv administration of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake. In four of these studies energy intake was significantly reduced following the glucagon-like peptide-1 infusion compared with saline. In the remaining studies, no significant effect of glucagon-like peptide-1 could be shown. Lack of statistical power or low glucagon-like peptide-1 infusion rate may explain these conflicting results. Our aim was to examine the effect of glucagon-like peptide-1 on subsequent energy intake using a data set composed of subject data from previous studies and from two as yet unpublished studies. Secondly, we investigated whether the effect on energy intake is dose dependent and differs between lean and overweight subjects. Raw subject data on body mass index and ad libitum energy intake were collected into a common data set (n = 115), together with study characteristics such as infusion rate, duration of infusion, etc. From four studies with comparable protocol the following subject data were included if available: plasma concentrations of glucagon-like peptide-1, subjective appetite measures, well-being, and gastric emptying rate of a meal served at the start of the glucagon-like peptide-1 infusion. Energy intake was reduced by 727 kJ (95% confidence interval, 548-908 kJ) or 11.7% during glucagon-like peptide-1 infusion. Although the absolute reduction in energy intake was higher in lean (863 kJ) (634-1091 kJ) compared with overweight subjects (487 kJ) (209-764 kJ) (P = 0.05), the relative reduction did not differ between the two groups (13.2% and 9.3%, respectively). Stepwise regression analysis showed that the glucagon-like peptide-1 infusion rate was the only independent predictor of the reduction in energy intake during glucagon-like peptide-1 (7-36) amide infusion (r = 0.4, P < 0.001). Differences in mean plasma glucagon-like peptide-1 concentration on the glucagon-like peptide-1 and placebo day (n = 43) were related to differences in feelings of prospective consumption (r = 0.40, P < 0.01), fullness (r = 0.38, P < 0.05), and hunger (r = 0.26, P = 0.09), but not to differences in ad libitum energy intake. Gastric emptying rate was significantly lower during glucagon-like peptide-1 infusion compared with saline. Finally, well-being was not influenced by the glucagon-like peptide-1 infusion. Glucagon-like peptide-1 infusion reduces energy intake dose dependently in both lean and overweight subjects. A reduced gastric emptying rate may contribute to the increased satiety induced by glucagon-like peptide-1.

Community participation in health: perpetual allure, persistent challenge.

The concept of community participation continues to capture the attention of international health policymakers and analysts nearly a quarter of a century after it was formally introduced at the Alma Ata Conference. This paper reviews trends in the participation literature of the 1990s, drawing examples primarily from Latin America. The following topics are discussed: sustainability, new methods for operationalizing and evaluating participation, the significance of local and cultural variability in determining outcomes, participatory self-determination as raised in the social movements literature, the increasing importance of intersectoral linkages, and continuing impediments posed by biomedical ideologies and systems. While the rhetoric and practice of participation have become fully integrated into mainstream health and development discourses, the paper concludes that ideological and political disagreements continue to divide pragmatists, who favour utilitarian models of participation, from activists, who prefer empowerment models.

Nutrient regulation of post-heparin lipoprotein lipase activity in obese subjects.

This study examines the immediate effect of ingestion of oral carbohydrate and fat on lipoprotein lipase (LPL) activity post-heparin in six lean and six obese age-matched women. Subjects were given, on two separate occasions, 340 kcal carbohydrate or an equicaloric amount of fat, both in 300 ml of water. Post-heparin LPL activity (10,000 U) was measured on each occasion 120 minutes after ingestion of the meal. Following oral carbohydrate postprandial plasma insulin levels were significantly higher in obese subjects than in lean (p < 0.01). Impaired glucose tolerance was seen in the obese group. GIP secretion was similar in lean and obese subjects both during oral fat and carbohydrate ingestion. GLP-1 secretion post-carbohydrate was lower in obese subjects. Total LPL activity unadjusted for body weight was similar in the two groups after carbohydrate administration but was significantly lower when adjusted per kg body weight. Total LPL activity was lower in the lean group at 130 minutes after fat administration (p < 0.02). Fasting serum triglycerides were higher in the obese group and were inversely related to the post-carbohydrate LPL activity (r = - 0.65, p < 0.02). Intraluminal lipoprotein lipase activity is not increased in established obesity. Fat and carbohydrate nutrients may affect LPL activity differently in lean and obese subjects.

Detection of glycated gastric inhibitory polypeptide within the intestines of diabetic obese (ob/ob) mice.

Gastric inhibitory polypeptide (GIP) is produced within endocrine cells of the small intestine and released into the circulation upon nutrient ingestion. This study has quantified the levels of this insulinotropic peptide in the intestines of lean and diabetic obese ob/ob mice and estimated the proportion that is glycated. The total intestinal GIP concentration and content of the diabetic mice were significantly greater (p < 0.01) than that of control animals. Affinity chromatographic separation and side-viewing GIP radioimmunoassay demonstrated that approx 20% of the GIP extracted from intestines of ob/ob mice was present in glycated form. Less than 2% of intestinal GIP was glycated in lean mice. In conclusion substantial quantities of glycated GIP exist within the intestines of diabetic ob/ob mice, suggesting that this may be a contributing factor to the physiological disarray of this syndrome.

Maternal and early dietary fatty acid intake: changes in lipid metabolism and liver enzymes in adult rats.

Over the last decade, much evidence has emerged to suggest that alterations in maternal nutrition during pregnancy may irreversibly affect aspects of physiological and biochemical functions in the fetus. This study was designed to determine the mechanisms involved in these alterations. Our hypothesis was that the type of maternal dietary fat received in early life could determine the level of lipoprotein lipase (LPL; EC 3.1.1.34) activity and gene expression which would be maintained into later life. A diet high in (n-3) polyunsaturated fatty acids was predicted to be associated with higher levels of lipoprotein lipase (LPL) activity and expression and lower levels of plasma triglyceride after a high fat meal challenge. Using a 2x2 factorial design, Wistar Albino rats were pair-fed either a fish oil diet (50 g/kg) or a mixed oil diet (50 g/kg) for the last 2 wk of gestation, during lactation and pups were fed these diets until 5 wk of age. After 5 wk, the rats were fed nonpurified diet. The rats were killed at 5 wk (young) or 10 wk (adult) of age after a mixed oil (50 g/kg) test meal. There were significant age effects on plasma triglyceride (P<0.02), cholesterol (P<0.001), glucose-dependent insulinotrophic polypeptide (GIP) (P<0.001) and liver glutathione reductase activity (P<0.05) which were all higher in the young rats compared to the adults. There were significant effects of diet on triglyceride (P<0.001), cholesterol (P<0.001) and LPL mRNA levels (P<0.001). GIP and triglyceride levels were significantly correlated (r = 0.66; P<0.001). Omental adipose tissue LPL activity as significantly higher in the fish-oil fed groups compared to the other groups (P<0.001), whereas Epididymal adipose tissue LPL mRNA was significantly higher in the mixed oil-fed adults compared to the other groups (P<0.001). The latter result suggested an imprinting effect of fatty acid composition in early life on LPL gene expression. Liver superoxide dismutase activity was affected by age and diet and was higher in the young than in the adults and higher in the fish oil-fed young than in those fed the mixed oil-fed (P<0.005). Catalase activity was also affected by age (P<0.001) and diet (P<0.001), and there was a significant interaction between age and diet (P<0.001). Catalase activity was higher in rats fed fish oils at both stages of development, suggesting that feeding fish oils to rats in early life raises oxidative stress throughout life. The majority of the significant differences shown were between the age groups and not between the two dietary groups, suggesting that postprandial handling of a standard fat meal is affected more by age than by early dietary fatty acid composition. However, the mechanisms of biological imprinting of fatty acids on LPL expression and on enzymes related to oxidative stress requires more investigation.

Diurnal variations in peripheral insulin resistance and plasma non-esterified fatty acid concentrations: a possible link?

Glucose tolerance becomes impaired towards the evening. Increased peripheral insulin resistance may be responsible, at least in part, for this effect. The mechanism for the diurnal variation in insulin sensitivity is undefined. It is, however, possible that variations in non-esterified fatty acids (NEFA) could contribute to this variation because NEFA have been implicated in the pathogenesis of insulin resistance. Therefore, we have investigated insulin sensitivity and plasma NEFA responses to insulin at 0830 h and 2030 h in nine healthy men by measuring arterialized plasma glucose and venous plasma NEFA concentrations during a short insulin tolerance test. The studies were standardized for a period of fasting, pre-test meal and exercise. Insulin sensitivity measured KITT was greater (P < 0.05) in the morning [(20 +/- 7) x 10(-3) mmol/L/min] than in the evening [(11.6 +/- 2) x 10(-3) mmol/L/min]. Fasting NEFA levels were lower (P < 0.01) in the morning (373 +/- 84 mumol/L) than in the evening (913 +/- 122 mumol/L). Following insulin, NEFA fell more slowly (P < 0.01) in the morning (149 +/- 26 mumol/L/15 min) than in the evening (491 +/- 91 mumol/L/15 min). These results confirm diurnal variations in insulin sensitivity and plasma NEFA concentrations irrespective of feeding and exercise. We speculate that the relatively elevated plasma NEFA levels in the evening are the cause rather than the consequence of increased insulin resistance at this time.

Inhibition of insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion by octreotide has no effect on post-heparin plasma lipoprotein lipase activity.

This study examines the immediate effect of modulating postprandial insulin and insulinotropic hormone (glucose-dependent insulinotropic polypeptide, GIP; glucagon-like peptide-1, GLP-1) secretion on the activation of lipoprotein lipase (LPL) in six lean and six obese age-matched women. Subjects were given, on two separate occasions, 340 kcal of carbohydrate alone or combined with an IV infusion of octreotide, (100 microg infusion from 30 min before the meal for 150 min). Post-heparin LPL activity (10,000 U) was measured on each occasion 120 minutes post-carbohydrate. Following oral carbohydrate postprandial plasma insulin levels were significantly higher in obese subjects than in lean (p < 0.01). Glucose tolerance was slightly impaired in obese subjects. Insulin, GIP and GLP-1 secretion post-carbohydrate was markedly reduced by octreotide in lean and obese subjects. LPL activity was similar in the two groups after carbohydrate administration and was unaffected by octreotide. Inhibition of postprandial insulin, GIP and GLP-1 secretion acutely did not reduce post-heparin LPL activity either in lean or obese subjects.

The influence of the colon on postprandial glucagon-like peptide 1 (7-36) amide concentration in man.

Glucagon-like peptide (7-36) amide (GLP-1) is an incretin hormone of the enteroinsular axis released rapidly after meals despite the fact that GLP-1 secreting cells (L-cells) occur predominantly in the distal gut. The importance of these colonic L-cells for postprandial GLP-1 was determined in healthy control subjects and in ileostomy patients with minimal small bowel resection (<5 cm). Subjects were fed a high complex carbohydrate test meal (15.3 g starch) followed by two carbohydrate-free, high fat test meals (25 g and 48.7 g fat respectively). Circulating levels of glucose, insulin, glucagon, glucose insulinotrophic peptide (GIP) and GLP-1 were measured over a 9-h postprandial period. For both subject groups the complex carbohydrate test meal failed to elicit a rise in either GIP or GLP-1. However, both hormones were elevated after the fat load although the GLP-1 concentration was significantly reduced in the ileostomist group when compared with controls (P=0.02). Associated with this reduction in circulating GLP-1 was an elevation in glucagon concentration (P=0.012) and a secondary rise in the plasma glucose concentration (P=0.006). These results suggest that the loss of colonic endocrine tissue is an important determinant in the postprandial GLP-1 concentration. Ileostomists should not be assumed to have normal enteroinsular function as the colon appears to have an important role in postprandial metabolism.

No effect of glucagon-like peptide-1 on short-term satiety and energy intake in man.

Centrally administered glucagon-like peptide-1 (GLP-1) inhibits feeding in fasted rats, but its role in human satiety has been largely unexplored. The present study investigated the effect of peripheral GLP-1 infusion on gastric emptying and satiety in man. Ten non-obese male subjects were infused in a randomized single-blind within-subject crossover study using saline infusion as control. They received either a GLP-1 infusion (1.2 pmol/kg per min) or a saline infusion for 1 h, at 18.00 hours. At 20 min after starting the infusion the gastric emptying of a 400 ml water load was measured. Subjects completed behavioural self-rating scales to assess hunger and satiety. After 40 min subjects were given a buffet meal ad libitum and their food intake was recorded. GLP-1 infusion raised circulating GLP-1 concentrations to approximately twice those seen following a meal. It did not affect circulating insulin levels but caused a small fall in glucose levels. Gastric emptying of the water load was significantly delayed by the GLP-1 infusion. Energy intake from the buffet was unaffected by GLP-1 infusion. Self-assessment of hunger and satiety was similarly unaffected by the infusion before the buffet meal, although subjects tended to be less hungry after the buffet meal following GLP-1 infusion (P < 0.09). GLP-1 infusion delayed gastric emptying but had a minimal effect on food intake and satiety. This study casts doubts on whether GLP-1 is a major satiety factor in man, although a raised circulating plasma glucose level, as would normally occur postprandially, might be necessary for GLP-1 to increase satiety.