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Intestinal glucose absorption is integral to postprandial glucose homeostasis. Glucose absorption is dependent on a number of factors, including the exposure of carbohydrate to the mucosa of the upper gastrointestinal tract (determined particularly by the rates of gastric emptying and small intestinal transit), the digestion of complex carbohydrate into monosaccharides, and glucose sensing and transport by the intestinal mucosa. The absorption of glucose in the small intestine is not only a determinant of the appearance of exogenous glucose in the peripheral circulation, but is also coupled to the release of gastrointestinal hormones that in turn influence postprandial glucose metabolism through modulating gastrointestinal motor function, insulin and glucagon secretion, and subsequent energy intake. This review describes the physiology and pathophysiology of intestinal glucose absorption in health and type 2 diabetes, including its relevance to glucose tolerance and the management of postprandial hyperglycaemia.

OBJECTIVE: Postprandial hypotension occurs frequently in older survivors of critical illness at 3 months after discharge. We aimed to determine whether postprandial hypotension and its predictors — gastric dysmotility and cardiovascular autonomic dysfunction — persist or resolve as older survivors of critical illness recover, and whether postprandial hypotension after intensive care unit (ICU) discharge is associated with adverse outcomes at 12 months. DESIGN: Prospective observational study. SETTING: Tertiary medical–surgical ICU. PARTICIPANTS: Older adults (aged > 65 years) who had been studied 3 months after ICU discharge and who returned for a follow-up study at 12 months after discharge. MAIN OUTCOME MEASURES: On both occasions after fasting overnight, participants consumed a 300 mL drink containing 75 g glucose, radiolabelled with 20 MBq 99mTcphytate. Blood pressure, heart rate, blood glucose concentration and gastric emptying rate were measured concurrently before and after ingestion of the drink. Falls, quality of life, hospitalisation and mortality rates were also quantified. RESULTS: Out of 35 older adults studied at 3 months, 22 returned for the follow-up study at 12 months. Postprandial hypotension was evident in 29% of participants (95% CI, 14–44%) at 3 months and 10% of participants (95% CI, 1–30%) at 12 months. Postprandial hypotension at 3 months was associated with a more than threefold increase in the risk of falls in the year after ICU discharge (relative risk, 3.7 [95% CI, 1.6–8.8]; P = 0.003). At 12 months, gastric emptying was normal (mean time taken for 50% of gastric contents to empty, 101.6 [SD, 33.3] min) and cardiovascular autonomic dysfunction prevalence was low (9% [95% CI, 1–29%]). CONCLUSIONS: In older adults who were evaluated 3 and 12 months after ICU discharge, postprandial hypotension at 3 months was associated with an increased risk of subsequent falls, but the prevalence of postprandial hypotension decreased with time.

Background and aims: Whey protein and guar gum have both been reported to reduce postprandial glycemia in health and type 2 diabetes, associated with stimulation of glucagon-like peptide-1 (GLP-1) and/or slowing of gastric emptying. Our aim was to evaluate, in type 2 diabetes, the acute effects of low dose “preloads” of whey and guar, given alone or in combination before a meal, on postprandial glycemia, insulin, GLP-1, and gastric emptying. Methods: 21 patients with type 2 diabetes, managed by diet or metformin alone, were each studied on 4 days. They received a preload “shake” 15min before a mashed potato meal (368.5 kcal) labeled with 13C-octanoic-acid. The preloads comprised either (i) 17 g whey (W), (ii) 5 g guar (G), (iii) 17 g whey + 5 g guar (WG) each sweetened with 60 mg sucralose, and (iv) 60 mg sucralose alone (control; C), all dissolved in 150 mL water. Venous blood was sampled frequently for measurements of glucose, insulin, and GLP-1 concentrations. Gastric half-emptying time (T50) was calculated from breath 13CO2 excretion over 240 min. Results: Postprandial blood glucose concentrations were lower with W and WG compared to C (each P < 0.0001, treatment × time interaction), and lower after G than C only at 30min. Insulin, GLP-1, and glucagon concentrations were higher after W than WG, G, or C (P < 0.05, treatment × time interaction), without differences between the latter three. Gastric emptying was slower with W (T50: 179.6 ± 6.1 min, P < 0.05) and WG (T50: 197.6 ± 9.7 min, P < 0.0001) when compared to C (T50: 162.9 ± 6.2 min), but did not differ between G (T50: 171.3 ± 7.0) and C (P > 0.99). Conclusion: Both whey and whey/guar preloads reduced postprandial glycemia, associated with slowing of gastric emptying. Low dose guar was less effective as a preload for glucose-lowering and did not slow gastric emptying usc Refereed/Peer-reviewed

usc Background: The interaction of nutrients with the small intestine stimulates the secretion of numerous enteroendocrine hormones that regulate postprandial metabolism. However, differences in gastrointestinal hormonal responses between the macronutrients are incompletely understood. In the present study, we compared blood glucose and plasma hormone concentrations in response to standardised intraduodenal (ID) fat and glucose infusions in healthy humans. Methods: In a parallel study design, 16 healthy males who received an intraduodenal fat infusion were compared with 12 healthy males who received intraduodenal glucose, both at a rate of 2 kcal/min over 120 min. Venous blood was sampled at frequent intervals for measurements of blood glucose, and plasma total and active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon.Results: Plasma concentrations of the incretin hormones (both total and active GLP-1 and GIP) and glucagon were higher, and plasma insulin and blood glucose concentrations lower, during intraduodenal fat, when compared with intraduodenal glucose, infusion (treatment by time interaction: P < 0.001 for each). Conclusions: Compared with glucose, intraduodenal fat elicits substantially greater GLP-1, GIP and glucagon secretion, with minimal effects on blood glucose or plasma insulin in healthy humans. These observations are consistent with the concept that fat is a more potent stimulus of the ‘gut-incretin’ axis than carbohydrate Refereed/Peer-reviewed

Aims: Gastric emptying is a major determinant of postprandial glycaemia in both health and type 2 diabetes (T2DM); the potential impact of ethnicity on gastric emptying is unclear. We compared the rate of gastric emptying of a standardised meal and the associated glycaemic response in Han Chinese and Caucasian patients with T2DM.Methods: 14 Han Chinese and 14 Caucasian T2DM patients, managed by diet and/or metformin monotherapy, underwent concurrent measurements of gastric emptying and blood glucose for 240 min after a 99mTc-calcium phytate-labelled mashed potato meal.Results: Han Chinese patients were slightly younger (P < 0.05), and had a lower BMI (P < 0.05), than Caucasians. There were no differences in either HbA1c or fasting blood glucose between them. Gastric half-emptying time (T50) was shorter (P < 0.05) and the postprandial blood glucose increment greater (P < 0.05) in Han Chinese than Caucasian patients. Both the increment in blood glucose from baseline at 60 min and peak blood glucose were related inversely to T50 (P < 0.05 each).Conclusions: Han Chinese with relatively well-controlled T2DM have more rapid gastric emptying compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. These differences may inform the choice of management, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying.

Background & aims: Enteral nutrition is important in critically ill patients and is usually administered via a nasogastric tube. As gastric emptying is frequently delayed, and this compromises the delivery of nutrient, it is important that the emptying rate can be quantified. Methods: A comprehensive search of MEDLINE/PubMed, of English articles, from inception to 1 July 2014. References of included manuscripts were also examined for additional studies. Results: A number of methods are available to measure gastric emptying and these broadly can be categorised as direct- or indirect-test and surrogate assessments. Direct tests necessitate visualisation of the stomach contents during emptying and are unaffected by liver or kidney metabolism. The most frequently used direct modality is scintigraphy, which remains the 'gold standard'. Indirect tests use a marker that is absorbed in the proximal small intestine, so that measurements of the marker, or its metabolite measured in plasma or breath, correlates with gastric emptying. These tests include drug and carbohydrate absorption and isotope breath tests. Gastric residual volumes (GRVs) are used frequently to quantify gastric emptying during nasogastric feeding, but these measurements may be inaccurate and should be regarded as a surrogate measurement. While the inherent limitations of GRVs make them less suitable for research purposes they are often the only technique that is available for clinicians at the bedside. Conclusions: Each of the available techniques has its strength and limitations. Accordingly, the choice of gastric emptying test is dictated by the particular requirement(s) and expertise of the investigator or clinician. Refereed/Peer-reviewed

We have shown that the capacity of 25 g whey preloads to slow gastric emptying and reduce post prandial glycaemia persists after 4 weeks regular exposure in patients with diet controlled type 2 diabetes. This dietary strategy therefore appears feasible for larger clinical trials to evaluate beneficial effects on long-term glycaemic control. Registered with the Australian New Zealand Clinical Trials Registry:ACTRN12614000831684. Refereed/Peer-reviewed

usc Postprandial hypotension occurs frequently in diabetes. We show in 9 type 2 patients, that the fall in systolic blood pressure is greater in response to intraduodenal glucose infused at 4 kcal/min than 2 kcal/min, implying that strategies to slow gastric emptying may be effective in the management of postprandial hypotension. Refereed/Peer-reviewed

Aims: To determine the prevalence of low faecal elastase-1 (FE-1) (≤200 μg/g) in type 2 diabetes (T2DM), and to test the hypothesis that pancreatic enzyme replacement therapy (PERT) would reduce postprandial glycaemia after a high-fat, high-carbohydrate meal in T2DM subjects with low FE-1. Methods: Of 109 community-based patients who submitted stool samples, 10 had low FE-1 and 8 were recruited (6 male, 2 female, 67.8 ± 3.0 years). Participants were given a high-fat, high-carbohydrate meal (718 kcal) with either pancrelipase (50,000 units) or placebo in a randomised, double-blind, crossover fashion. The primary outcome was the difference in postprandial glycaemia following PERT vs placebo, as evaluated by the incremental area under the postprandial plasma glucose curve (iAUC). Secondary outcomes included differences in gastric half-emptying time (T50) measured using scintigraphy, and C-peptide iAUC. Results: The prevalence of low FE-1 in T2DM was 9.2% (95% CI 3.8–14.6%). There was no difference in postprandial glycaemia iAUC (P = 0.38), gastric emptying T50 (P = 0.69) or C-peptide iAUC (P = 0.25) after PERT compared to placebo. Conclusions: Decreased FE-1 has a relatively low prevalence in community-based patients with T2DM, and PERT does not reduce postprandial glycaemia in these patients. Clinical Trial Registration Number: ACTRN12617000349347. usc Refereed/Peer-reviewed

Background Postprandial hypotension (PPH) occurs frequently in older individuals with disease and/or living in residential care, but its prevalence in "healthy" older individuals has not been evaluated in large cohorts. PPH is associated with substantial morbidity and increased mortality; current management is suboptimal. Recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is related to the rate of gastric emptying (GE), so that relatively more rapid GE may potentially be a risk factor for PPH. We aimed to determine the prevalence of, and evaluate the association of GE with PPH. Methods A total of 88 healthy "older", community-dwelling residents (47 women, 41 men; age 71.0 ± 0.5 years) attended a clinical research laboratory on a single occasion. Individuals consumed a 300 mL drink containing 75 g glucose and 150 mg C 13 -acetate. Exhaled breath was obtained for analysis of 13 CO 2 and calculation of the 50% GE time (T 50 ). BP and heart rate were assessed with an automated device. Results Eleven (12.8%) of 86 subjects had PPH (2 had diabetes and were excluded). GE was faster in subjects with PPH than the remainder of the group (T 50 118.0 ± 9.4 vs 142.3 ± 4.6 minutes, P Conclusions We conclude the prevalence of PPH in a cohort of otherwise healthy "older" individuals is 12.8% and PPH is associated with relatively more rapid GE. Therapies that slow GE may be useful in the management of PPH.

Multiple studies have reported prenatal stress as a potential risk factor for the development of autism spectrum disorder (ASD). In rodents, a significant reduction in sociability is seen in prenatally stressed offspring of genetically stress-susceptible dams. Certain dietary factors that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in adult offspring. Adults with a diet rich in omega-6 polyunsaturated fatty acids (PUFAs) display increased stress reactivity. In the current study, the effects of prenatal diet and prenatal stress on social behavior in adult offspring mice were examined. Pregnant C57BL/6J dams received either chronic variable stress or no stress, and were also placed on a control diet or a diet rich in omega-6 PUFAs, in a 2×2 design. We subsequently tested the adult offspring for sociability, anxiety, and locomotor behaviors using a 3-chambered social approach task, an elevated-plus maze, an open field task and a rotarod task. Results indicated that a maternal diet rich in omega-6 PUFAs during gestation and lactation produce changes in sociability consistent with those observed in ASD. Additionally, offspring exposed to a diet rich in omega-6 PUFAs during gestation and lactation had increased levels of anxiety in the elevated-plus maze. Prenatal stress had no effect on offspring behavior. These findings provide evidence for a possible environmental risk factor that contributes to the production of autistic-like behavior in mice.

Background: Macronutrient “preloads” can stimulate glucagonlike peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. Objective: We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. Design: Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a 13 C-octanoic acid–labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. Results: Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P , 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P , 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P , 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P , 0.05). Conclusions: In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910. Am J Clin Nutr doi: 10.3945/ajcn.111.021543.

Background: Dietary interventions represent a promising therapeutic strategy to optimize postprandial glycemia. The addition of protein to oral glucose has been reported to improve the glycemic profile. Objective: The aim of the current study was to evaluate the mechanisms by which protein supplementation lowers the blood glucose response to oral glucose. Design: Nine healthy men were studied on 3 d each in a random order. Subjects consumed 300-mL drinks containing either 50 g glucose (Glucose), 30 g gelatin (Protein), or 50 g glucose with 30 g gelatin (Glucose + Protein) in water labeled with 150 mg [ 13 C]acetate. Blood and breath samples were subsequently collected for 3 h to measure blood glucose and plasma insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations and gastric half-emptying time, which was calculated from 13 CO 2 excretion. Results: The blood glucose response was less after Glucose + Protein than after Glucose (P < 0.005); GIP was lower (P < 0.005), and there were no significant differences in plasma insulin or GLP-1. Protein alone stimulated insulin, GLP-1, and GIP (P < 0.05 for each) without elevating blood glucose. The gastric half-emptying time was greater after Glucose + Protein than after Glucose (P < 0.05) and tended to be greater for Glucose than for Protein (P = 0.06). Conclusions: In healthy humans, the addition of protein to oral glucose lowers postprandial blood glucose concentrations acutely, predominantly by slowing gastric emptying, although protein also stimulates incretin hormones and non-glucose-dependent insulin release.

The effects of fat on gastric emptying (GE), gut hormones, and energy intake are dependent on digestion to free fatty acids (FFAs). In animals, small intestinal oleic acid inhibits energy intake more potently than the triacylglyceride (TG) triolein, but there is limited information about the comparative effects of FFA and TG in human beings. We compared the effects of FFA and TG on GE, gut hormone secretion, appetite, and energy intake in healthy males.Nine men (age, 23 +/- 2 y; body mass index, 22 +/- 1 kg/m(2)) were studied on 3 occasions to evaluate the effects of (1) 40 g oleic acid (FFA, 1830 kJ), (2) 40 g macadamia oil (TG, 1856 kJ; both 600-mL oil-in-water emulsions stabilized with 4% milk protein and labeled with 15 MBq (123)I), or (3) 600 mL 4% milk protein (control, 352 kJ), administered intragastrically, on GE, plasma cholecystokinin (CCK) and peptide-YY (PYY) levels, appetite perceptions, and subsequent energy intake.GE of FFA was much slower than that of TG (P.05), with greater retention of FFA, than TG, in the proximal stomach (P.001). Hunger was less (P.05), and fullness was greater (P.05), after FFA when compared with control and TG. Increases in plasma CCK and PYY levels were greater after FFA than TG or control (P.05). Energy intake tended to be less after FFA compared with TG (control, 4754 +/- 610 kJ; TG, 5463 +/- 662 kJ; FFA, 4199 +/- 410 kJ).FFAs empty from the stomach more slowly, but stimulate CCK and PYY and suppress appetite more potently than TG in healthy human beings.

Purpose To evaluate the natural history of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. Subjects and methods We enrolled 20 patients (6 men, 14 women) with diabetes mellitus (16 with type 1 diabetes, 4 with type 2 diabetes). Each had measurements of gastric emptying of a solid (100 g of ground beef) and liquid (150 mL of 10% dextrose) meal using scintigraphy, glycemic control (glycosylated hemoglobin [HbA 1c ] and mean blood glucose levels), upper gastrointestinal symptoms, and autonomic nerve function at baseline and after a mean (± SD) of 12.3 ± 3.1 years of follow-up. Results There were no differences in mean gastric emptying of the solid component (retention at 100 minutes at baseline: 56% ± 19% vs. follow-up: 51% ± 21%, P = 0.23) or the liquid component (time for 50% to empty at baseline: 33 ± 11 minutes vs. follow-up: 31 ± 12 minutes, P = 0.71) during follow-up. Mean blood glucose (17.0 ± 5.6 mmol/L vs. 13.8 ± 4.9 mmol/L, P = 0.007) and HbA 1c (8.4% ± 2.3% vs. 7.6% ± 1.3%, P = 0.03) levels were lower at follow-up. There was no difference in symptom score (baseline: 3.9 ± 2.7 vs. follow-up: 4.2 ± 4.0, P = 0.78). There was evidence of autonomic neuropathy in 7 patients (35%) at baseline and 16 (80%) at follow-up. Conclusion In patients with diabetes mellitus, we did not observe any marked changes in either gastric emptying or upper gastrointestinal symptoms during a 12-year period.

Background: Aging is associated with a decrease in appetite and a slowing of gastric emptying. The gastrointestinal hormones cholecystokinin (CCK), glucagon-like peptide I (GLP-I), and peptide YY (PYY) may mediate these changes. Objective: We investigated whether aging influenced the secretion of CCK, GLP-1, and PYY and their effects on appetite and pyloric motility. Design: Eight healthy older (65-80 y) and 7 younger (20-34 y) men received isoenergetic (12.1 kJ/min) intraduodenal infusions of lipid and glucose for 120 min on separate days. Plasma CCK, GLP-1, and PYY concentrations were measured. Results: Plasma CCK concentrations were higher in older than in younger subjects (P = 0.004) as a result of higher baseline values (4.7 ± 0.2 compared with 3.2 ± 0.2 pmol/L; P < 0.0001) and a greater rise during lipid infusion (increase from baseline: 7.1 ± 0.5 compared with 5.3 ± 0.6 pmol/L; P = 0.048). Plasma GLP-I and PYY concentrations were not significantly different between groups. The decrease in hunger during intraduodenal lipid infusion was inversely related to the increase in CCK, GLP-I, and PYY in younger but not older subjects. During intraduodenal lipid infusion, the increase in isolated pyloric pressure wave (IPPW) frequency was positively related to GLP-1 and PYY and the increase in IPPW amplitude was positively related to CCK in older but not younger subjects, whereas the increase in IPPW amplitude and pyloric tone was negatively related to GLP-1 and PYY in younger subjects. Conclusions: Human aging is associated with increased CCK concentrations, which may contribute to the slowing of gastric emptying, mediated by increased pyloric motility. The role of increased plasma CCK concentrations in mediating the age-related decrease in appetite remains to be established.

Glucagon-like peptide-1 (GLP-1) may play a role in regulating gastric emptying. The aim of this study was to determine the relationship between gastric emptying of glucose and plasma concentrations of GLP-1. Gastric emptying of 75 g of glucose dissolved in 350 ml of water was measured by the use of scintigraphy in 12 normal volunteers. Venous blood samples for measurement of GLP-1 were obtained immediately before and for 180 min after ingestion of glucose. Plasma GLP-1 rose rapidly from a baseline of 8.5 +/- 1.2 pmol/l to 14.3 +/- 1.3 pmol/l at 10 min (p = 0.024), with a peak of 19.2 +/- 3.0 pmol/l at 30 min (p = 0.0006) after the glucose drink. The rate of gastric emptying was inversely related to the early rise in GLP-1, e.g., the 50% emptying time was related to the change in GLP-1 from baseline at 10 min (r = 0.57; p < 0.05). We conclude that there is an inverse relationship between gastric emptying of glucose and plasma GLP-1. This observation is consistent with the concept that GLP-1 is a determinant of, rather than determined by, the rate of gastric emptying.

The factors influencing appetite in humans are poorly understood. There is a weak relation between appetite and gastric emptying in normal subjects. Recent studies have shown that fasting and postprandial antral areas increase in patients with functional dyspepsia compared with normal subjects. We evaluated the hypothesis that antral area, and hence antral distention, is a significant determinant of postprandial fullness. Fourteen normal subjects had simultaneous measurements of gastric emptying by scintigraphy and antral area by ultrasound after ingestion of 350 mL 20% glucose. Fullness and hunger were assessed by visual analog scales. Measurements of the gastric-emptying half time (t1/2) by scintigraphy and ultrasound were not significantly different (129.6 +/- 11.8 min compared with 115.6 +/- 11.4 min). Fullness increased (P0.001) and hunger decreased (P0.001) after the drink. Both fullness and the magnitude of the increase in fullness after the drink were related to antral area (r0.56, P0.05), the increase in antral area (r0.59, P0.05), and the scintigraphic content of the distal stomach (r0.57, P0.05), but not to the ultrasound or scintigraphic t1/2 values. In contrast, hunger and the magnitude of the decrease in hunger after the drink were not related to either antral area, the increase in antral area, or the rate of gastric emptying. We conclude that postprandial fullness, but not hunger, was closely related to antral distention in normal subjects.

The preparations of: (a) the iodides (Me 3 Si) 2 C(SiMe 2 C 6 H 4 Y)(SiMe 2 I) (Y = H, p - OMe, p -Me, p -Cl, m -CF 3 ), via the corresponding hydrides; (b) the compounds (Me 3 Si) 2 C(SiMe 2 Ph)(SiMe 2 X) with X = F, O 2 CCF 3 , O 2 CCH 3 , OMe, N 3 , NCS and Cl; and (c) the iodide (p-MeC 6 H 4 ) 3 CSiMe 2 I are described.

The iodides (Me 3 Si) 2 C(SiMe 2 C 6 H 4 Y)(SiMe 2 I), with Y  H, p -OMe, and p -Cl, react with trifluoroacetic acid at 35°C to give the bis(trifluoroacetate) (Me 3 Si) 2 C(SiMe 2 O 2 CCF 3 ) 2 , 8 . The initial reaction involves solvolysis at the SiI bond to give HI and (Me 3 Si) 2 C(SiMe 2 C 6 H 4 Y)(SiMe 2 OCCF 3 ), and the HI then cleaves the Si-aryl bond in the latter and in the starting material to give (Me 3 Si)C(SiMe 2 I)(SiMe 2 O 2 CCF 3 ) and (Me 3 Si) 2 C(SiMe 2 I) 2 , which then undergo further solvolysis, with anchimeric assistance by γ-O 2 CCF 3 or γ-I to leaving of I − . In the case of the corresponding reaction of the bromide (Me 3 Si) 2 C(SiMe 2 Ph)(SiMe 2 Br) the dibromide is clearly seen as an intermediate. In keeping with the above, when Et 3 N is present to neutralize the HI the reaction of (Me 3 Si) 2 C(SiMe 2 C 6 H 4 Cl- p )(SiMe 2 I) gives only the expected (Me 2 Si) 2 C(SiMe 2 C 6 H 4 Cl- p )(SiMe 2 O 2 CCF 3 ). The reactions of the compounds (Me 3 Si) 2 C(SiMe 2 Ph)(SiMe 2 OR), R  Me or H, also give 8 , but the initial reaction is cleavage of the SiPh bond by CF 3 CO 2 H, and it is suggested that this process is assisted by initial protonation of the OR group followed by transfer of the proton to the nearby ipso carbon atom of the phenyl group.

portioned by service personnel using standardized portioning tableware. Energy (KJ) and protein (g) intakes were estimated by nursing staff using three visual methods: Method A: Food registration (each item, meat/fish, vegetables, potatoes, sauce) Method B: Reduced Plate Method (consumed 0, 25, 50 or 100%) Method C: Plate Method (consumed 0, 25, 50, 75 or 100%) As reference method separate weighting of all food items preand post serving was used. Results are given as median and [25%>, 75%> percentiles]. Wilcoxon Signed Rank Test was used, Alpha level 0.05. Results: The total energy served pr. lunch meal was 893.6 KJ [830.4 1034.3] and the weighed intake 676.6 kJ [421.4 870.0]. The median intake estimated by method A: 663.0 KJ [389.0 873.0] (p = 0.044), method B: 487.8 KJ [316.5 873.0] (p < 0.001) and method C: 636.0 KJ [436.5 873.0] (p < 0.001) respectively. The weighted protein content pr. served meal was 13.0 g [11.4 15.4] with a weighted intake of 10.3 g [5.3 13.1]. The median intake estimated by method A: 10.7 g [5.3 11.7] (P= 0.045), method B: 8.0 g [4.8 11.7] (p < 0.001) and method C: 9.3 g [5.8 11.7] (p < 0.001). Conclusion: All visual methods underestimated energy intake. Methods B and C underestimated protein intake whereas method A overestimated protein intake. However, best estimates was found using method A.

Acute hyperglycaemia slows gastric emptying, reduces proximal gastric tone, inhibits antral motility, and stimulates pyloric contractions. The mechanisms mediating these effects are unknown, but nitric oxide (NO), a key inhibitory neurotransmitter in the gut, could potentially be involved. Aim: To determine whether the NO synthase inhibitor, L-NAME, reverses the effects of hyperglycaemia on gastric emptying and proximal and distal gastric motility. Methods: Seven healthy volunteers (4 male; age 30.3±3.8 yr; BMI 23.6±1.2 kg/m2) were studied in a 4-way randomised crossover design (hyperglycaemia vs. euglycaemia; L-NAME vs. placebo) after an overnight fast. After positioning a transnasal manometry catheter across the pylorus, the blood glucose was maintained at either 15 mmol/L or 5 mmol/L using a glucose/insulin clamp. Once the blood glucose was stabilised for 30 min, an intravenous infusion of L-NAME (180 mcg/kg/h) or placebo (0.9% saline) was commenced (t = 0) and continued for 150 min. At t = 30, subjects ingested a test drink containing 50g glucose made up to 300ml with water. Gastric emptying and intragastric distribution (proximal and distal stomach retention) were measured using 3-D ultrasound. Antropyloroduodenalmotility was recorded concurrently. Statistical analysis was performed using repeated measures ANOVA. Data presented as mean ± SEM. Results: Gastric half-emptying time (T50) was prolonged on the hyperglycaemia/placebo day compared to the remaining 3 study days, which were no different from each other (127±19min [hyperglycaemia/placebo] vs. 86±7min [hyperglycaemia/L-NAME] vs. 77±12min [euglycaemia/placebo] vs. 81±5min [euglycaemia/ L-NAME]; P = 0.01). The effect of hyperglycaemia on gastric emptying was completely abolished by L-NAME. The rate of total gastric emptying closely correlated to that of proximal (r = 0.970; P < 0.0001), but not distal (P = N.S.), gastric emptying. Fasting antral motility index was suppressed during hyperglycaemia (P < 0.05). Basal pyloric pressure was increased during hyperglycaemia (P < 0.001), and decreased with L-NAME (P < 0.001). Conclusions: Hyperglycaemia-induced delay in gastric emptying is associated with increased proximal retention and increased basal pyloric pressure; these effects are attenuated markedly by L-NAME.

BACKGROUND: There is evidence that the menstrual cycle affects appetite, such that energy intake is lower pre-ovulation than post-ovulation (Li et al, Appetite 1999; 33:109-118). Since changes in gastric emptying (GE) contribute to acute energy intake, an understanding of how the menstrual cycle affects GE is important. Furthermore, knowledge on day-to-day variations in energy intake, i.e. within the same phase of the menstrual cycle, is limited. AIMS: To assess the hypotheses that (i) GE is slower, and hunger and energy intake are less, pre-ovulation than post-ovulation, (ii) GE and energy intake are reproducible when assessed twice within a particular phase of the menstrual cycle (eg pre-ovulation) and (iii) the reduction in hunger and energy intake pre-ovulation will be related to slower GE. METHODS: 9 healthy, lean females (aged 32±1 years; BMI: 21.6±0.5 kg/m2) were studied on 3 separate occasions; twice pre-ovulation (between days 6-12; “Pre-V1” and “Pre-V2”), and once post-ovulation (between days 18-24; “Post”). Visits were randomized in singleblind fashion over consecutive menstrual cycles. Following consumption of a 300 ml glucose drink (815 kJ), GE (using 3D ultrasound) and hunger (using visual analogue scales) were measured for 90 min. Between 90-120 min, energy intake at a buffet meal was quantified. RESULTS: During pre-ovulation, GE was slower (P

Gastric emptying and intragastric distribution of a meal, and gastrointestinal hormones, including cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), play an important role in appetite regulation. Healthy, lean, young males have widely been used in studies evaluating energy intake. It has, however, been reported that there is marked inter-individual variability in energy intake in this group. Whether there is significant intra-individual variation in acute energy intake after a nutrient preload, and, if so, this relates to changes in gastric emptying and gastrointestinal hormone release, is unclear. We hypothesised that appetite/energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying and gastrointestinal hormone release. 15 healthy males consumed a glucose preload (50 g glucose in 300 ml water; 195 kcal) on 3 separate occasions. Gastric emptying and intragastric meal distribution (measured by 3D ultrasound), plasma CCK and GLP-1 and appetite perceptions were evaluated over 90 min, after which energy intake from a cold, buffet-style meal was quantified. Energy intake (kJ) and amount eaten (g) showed excellent agreement between visits (intraclass correlation coefficient, ri >0.8), while for macronutrient distribution, reproducibility was moderate to good (0.54 0.8), between days. Therefore, in healthy males, patterns of gastric emptying and gastrointestinal hormone secretion are highly reproducible, when measured repeatedly on separate occasions, and associated with reproducible energy intakes.

The effects of fat on gastric emptying, gastrointestinal hormone release and energy intake are dependent on the digestion of fat to free fatty acids (FFAs). There is limited information about the comparative effects of FFAs and triglycerides (TGs) on these factors. In animals, oleic acid inhibits energy intake more potently than an isocaloric infusion of its TG, triolein. Nine healthy males (23±2 years, BMI 22±1 kg/m 2 ) were studied on three occasions to evaluate the effects of (i) 40 g of oleic acid (“FFA”) (1830 kJ), (ii) 40 g of macadamia oil (“TG”) (1856 kJ) (both 600 ml oil-in-water emulsions stabilized with 4% milk protein and labelled with 15 MBq 123 I), or (iii) 600 ml 4% milk protein (“control”, 352 kJ), administered intragastrically, on gastric emptying, plasma CCK and PYY, appetite and energy intake. Gastric emptying of FFA was much slower than of TG ( P P P P P P Conclusion Free fatty acids empty from the stomach more slowly, but stimulate CCK and PYY release and suppress appetite and energy intake much more potently, than triglycerides.

Studies in animals indicate that endogenous nitric oxide (NO) is an important inhibitory neurotransmitter in the gastrointestinal tract and that it modulates food intake. We evaluate the role of NO mechanisms in mediating the effects of small intestinal nutrients on antropyloroduodenal motility and appetite in humans.On 2 separate days, 8 healthy adult men received intravenous L-NAME 180 microg/kg/h or 0.9% saline (0-150 min); between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole manometric assembly. During the infusions, perceptions of hunger and fullness were assessed with visual analog questionnaires and amount and macronutrient content of food consumed at the buffet meal were quantified. Blood pressure and heart rate were monitored at regular intervals.Intraduodenal lipid infusion was associated with increases in fullness (P0.05) and in frequency of isolated pyloric pressure waves (P0.05) and basal pyloric pressure (P0.05); and decreases in hunger (P0.05) and in frequency of antral (P0.05) and duodenal (P0.05) pressure waves. L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart rate (P0.05), but had no effect on antropyloroduodenal pressures or food intake.Intravenous administration of the systemic NO synthase inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy humans does not modify the antropyloroduodenal motor and appetite responses to intraduodenal lipid infusion.