Comparison of energy intake in critical illness survivors, general medical patients, and healthy volunteers: A descriptive cohort study.

BACKGROUND: Intensive care unit (ICU) survivors have reduced oral intake; it is unknown whether intake and associated barriers are unique to this group. OBJECTIVE: To quantify energy intake and potential barriers in ICU survivors compared with general medical (GM) patients and healthy volunteers. DESIGN: A descriptive cohort study in ICU survivors, GM patients, and healthy volunteers. Following an overnight fast, participants consumed a 200 ml test-meal (213 kcal) and 180 min later an ad libitum meal to measure energy intake (primary outcome). Secondary outcomes; taste recognition, nutrition-impacting symptoms, malnutrition, and quality of life (QoL). Data are mean ± SD, median (interquartile range [IQR]) or number [percentage]). RESULTS: Twelve ICU survivors (57 ± 17 years, BMI: 30 ± 6), eight GM patients (69 ± 19 years, BMI: 30 ± 6), and 25 healthy volunteers (58 ± 27 years, BMI: 25 ± 4) were included. Recruitment ceased early because of slow recruitment and SARS-CoV-2. Energy intake was lower in both patient groups than in health (ICU: 289 [288, 809], GM: 426 [336, 592], health: 815 [654, 1165] kcal). Loss of appetite was most common (ICU: 78%, GM: 67%). For ICU survivors, GM patients and healthy volunteers, respectively, severe malnutrition prevalence; 40%, 14%, and 0%; taste identification; 8.5 [7.0, 11.0], 8.5 [7.0, 9.5], and 8.0 [6.0, 11.0]; and QoL; 60 [40-65], 50 [31-55], and 90 [81-95] out of 100. CONCLUSIONS: Energy intake at a buffet meal is lower in hospital patients than in healthy volunteers but similar between ICU survivors and GM patients. Appetite loss potentially contributes to reduced energy intake.

A Biphasic Glucose Response during an Oral Glucose Tolerance Test Is Associated with Greater Plasma Insulin and GLP-1 Responses and a Reduction in 1-Hour Glucose but Does Not Relate to the Rate of Gastric Emptying in Healthy, Older Adults.

BACKGROUND: The pattern of the plasma glucose response curve during an oral glucose tolerance test (OGTT) is of prognostic significance with "biphasic" when compared with "monophasic" patterns being associated with greater insulin sensitivity/secretion and a reduced risk of progression to diabetes. The relationships of the glucose response curves with gastric emptying and incretin hormone secretion are not known. METHODS: Thirty-six adults (age > 65 years) without known diabetes consumed a 300 mL drink containing 75 g glucose and 150 mg C13-acetate at baseline and follow-up after 5.8 ± 0.1 years. Plasma glucose, glucagon-like peptide-1 (GLP-1), glucose independent insulinotropic polypeptide (GIP) and insulin were measured, and participants classified according to the pattern of their glucose response. Gastric emptying was measured on breath samples (stable isotope breath test). RESULTS: At baseline, 22 participants had a "monophasic" and 14 a "biphasic" glucose response. The 1 h plasma glucose response curve was greater and the GLP-1 AUC0-120 min and insulin secretion lower in the monophasic group. There were no differences in gastric emptying, GIP or insulin sensitivity. At the follow-up, the 1 h glucose response curve was greater again, while GLP-1 AUC0-120 min was lower in the monophasic group. CONCLUSIONS: A biphasic curve is associated with a higher 60 min glucose response curve and increases in GLP-1, but no difference in either GIP or gastric emptying.

Effect of gastric distension with concurrent small intestinal saline or glucose infusion on incretin hormone secretion in healthy individuals: A randomized, controlled, crossover study.

AIM: To evaluate the effect of gastric distension, induced using a gastric 'barostat', on the secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the presence and absence of small intestinal nutrients in healthy individuals. MATERIALS AND METHODS: Eight healthy participants (two females, six males, mean age 69.3 ± 1.2 years, body mass index 23.5 ± 0.8 kg/m2 ) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. RESULTS: Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP-1 with or without gastric distension (P = 1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P = 1.00 for saline infusion and P = .99 for glucose infusion). CONCLUSIONS: Gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans.

Disparities in the Glycemic and Incretin Responses to Intraduodenal Glucose Infusion Between Healthy Young Men and Women.

CONTEXT: Premenopausal women are at a lower risk of type 2 diabetes (T2D) compared to men, but the underlying mechanism(s) remain elusive. The secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), from the small intestine is a major determinant of glucose homeostasis and may be influenced by sex. OBJECTIVES: This study compared blood glucose and plasma insulin and incretin responses to intraduodenal glucose infusions in healthy young males and females. DESIGN: In Study 1, 9 women and 20 men received an intraduodenal glucose infusion at 2 kcal/min for 60 minutes. In Study 2, 10 women and 26 men received an intraduodenal glucose at 3 kcal/min for 60 minutes. Venous blood was sampled every 15 minutes for measurements of blood glucose and plasma insulin, GLP-1 and GIP. RESULTS: In response to intraduodenal glucose at 2 kcal/min, the incremental area under the curve between t = 0-60 minutes (iAUC0-60min) for blood glucose and plasma GIP did not differ between the 2 groups. However, iAUC0-60min for plasma GLP-1 (P = 0.016) and insulin (P = 0.011) were ∼2-fold higher in women than men. In response to intraduodenal glucose at 3 kcal/min, iAUC0-60min for blood glucose, plasma GIP, and insulin did not differ between women and men, but GLP-1 iAUC0-60min was 2.5-fold higher in women (P = 0.012). CONCLUSION: Healthy young women exhibit comparable GIP but a markedly greater GLP-1 response to intraduodenal glucose than men. This disparity warrants further investigations to delineate the underlying mechanisms and may be of relevance to the reduced risk of diabetes in premenopausal women when compared to men.

Acute Administration of the GLP-1 Receptor Agonist Lixisenatide Diminishes Postprandial Insulin Secretion in Healthy Subjects But Not in Type 2 Diabetes, Associated with Slowing of Gastric Emptying.

INTRODUCTION: It is uncertain whether lixisenatide has postprandial insulinotropic effects when its effect on slowing gastric emptying is considered, in healthy subjects and type 2 diabetes mellitus (T2DM). We evaluated the effects of single administration of 10 µg sc lixisenatide on glycaemia, insulin secretion and gastric emptying (GE), measured using the 'gold standard' technique of scintigraphy following an oral glucose load (75 g glucose). METHODS: Fifteen healthy subjects (nine men, six women; age 67.2 ± 2.3 years) and 15 patients with T2DM (nine men, six women; age 61.9 ± 2.3 years) had measurements of GE, plasma glucose, insulin and C-peptide for 180 min after a radiolabeled 75 g glucose drink on two separate days. All subjects received lixisenatide (10 µg sc) or placebo in a randomised, double-blind, crossover fashion 30 min before the drink. Insulin secretory response (ISR) was determined using the C-peptide deconvolution method. RESULTS: GE was markedly slowed by lixisenatide compared with placebo in both healthy subjects (1.45 ± 0.10 kcal/min for placebo vs. 0.60 ± 0.14 kcal/min for lixisenatide) and diabetes (1.57 ± 0.06 kcal/min for placebo vs. 0.75 ± 0.13 kcal/min for lixisenatide) (both P < 0.001) with no difference between the two groups (P = 0.42). There was a moderate to strong inverse correlation between the early insulin secretory response calculated at 60 min and gastric retention at 60 min with lixisenatide treatment in healthy subjects (r = - 0.8, P = 0.0003) and a trend in type 2 diabetes (r = - 0.4, P = NS), compared with no relationships in the placebo arms (r = - 0.02, P = NS, healthy subjects) and (r = - 0.16, P = NS, type 2 diabetes). CONCLUSION: The marked slowing of GE of glucose induced by lixisenatide is associated with attenuation in the rise of postprandial glucose in both healthy subjects and diabetes and early insulin secretory response in healthy subjects. CLINICAL TRIALS REGISTRATION NUMBER: NCT02308254.

Comparative effects of low-carbohydrate, full-strength and low-alcohol beer on gastric emptying, alcohol absorption, glycaemia and insulinaemia in health.

AIMS: The aim of this study was to evaluate the comparative effects of low-carbohydrate (LC), full-strength (FS), and low-alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health. METHODS: Eight subjects (four male, four female; age: 20.4 ± 0.4 years; BMI 22.7 ± 0.4 kg/m2 ) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc-calcium phytate, in random order. RESULTS: There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 ± 13.5 min vs LC: 79.5 ± 12.9 min vs LA: 74.6 ± 12.4 min; P = .39). Plasma ethanol was less after LA than LC (P < .001) and FS (P < .001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = -0.87, P < .01) and a trend for inverse relationships after LC (r = -0.67, P = .07) and FS (r = -0.69, P = .06). The AUC 0-180 min for blood glucose was greater for LA than LC (P < .001), with no difference between LA and FS (P = .40) or LC and FS (P = 1.0). CONCLUSION: In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response.

Measurement of Gastric Emptying Using a 13C-octanoic Acid Breath Test with Wagner-Nelson Analysis and Scintigraphy in Type 2 Diabetes.

INTRODUCTION: Breath tests utilising 13C-labelled substrates for the assessment of gastric emptying have been applied widely. Wagner-Nelson analysis is a pharmacokinetic model that can be utilised to generate a gastric emptying curve from the % 13CO2 measured in breath samples. We compared Wagner-Nelson analysis with (i) scintigraphy and (ii) conventional breath test modelling to quantify gastric emptying in type 2 diabetes. METHODS: Thirteen patients (age 68.1±1.5 years, body mass index 31.0±0.9 kg/m2, HbA1c 6.3±0.2%) consumed a mashed potato meal comprising 65 g powdered potato, 20 g glucose, 250 ml water, an egg yolk labelled with 100 µL 13C-octanoic acid and 20MBq 99mTc-calcium phytate. Scintigraphic data were acquired and breath samples collected for 4 hours after the meal. Gastric emptying curves were derived based on each technique; the 50% emptying time and intragastric retention at 60 min were also calculated. RESULTS: With Wagner-Nelson analysis, a Kel=0.60 (the elimination constant) best approximated the scintigraphic gastric emptying curve. There was a relationship between the T50 calculated with scintigraphy and by both Wagner-Nelson Kel=0.60 (r2=0.45, P<0.05) and conventional analysis (r2=0.44, P<0.05). There was no significant difference in the 50% gastric emptying time for scintigraphy (68.5±4.8 min) and Wagner-Nelson Kel=0.60 (71.3±4.5 min), however, the 50% gastric emptying time calculated by conventional analysis was much greater at 164.7±6.0 min (P<0.001). CONCLUSION: In type 2 diabetes, gastric emptying of a mashed potato meal measured using a 13C-octanoic acid breath test analysed with Wagner-Nelson Kel=0.60 closely reflects measurements obtained with scintigraphy, whereas, in absolute terms, the conventional breath test analysis does not.

Inconsistent relationship between depth of sedation and intensive care outcome: systematic review and meta-analysis.

PURPOSE: To determine the effect of depth of sedation on intensive care mortality, duration of mechanical ventilation, and other clinically important outcomes. METHODS: We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO from 2000 to 2020. Randomised controlled trials (RCTs) and cohort studies that examined the effect of sedation depth were included. Two reviewers independently screened, selected articles, extracted data and appraised quality. Data on study design, population, setting, patient characteristics, study interventions, depth of sedation and relevant outcomes were extracted. Quality was assessed using Critical Appraisal Skills Programme tools. RESULTS: We included data from 26 studies (n=7865 patients): 8 RCTs and 18 cohort studies. Heterogeneity of studies was substantial. There was no significant effect of lighter sedation on intensive care mortality. Lighter sedation did not affect duration of mechanical ventilation in RCTs (mean difference (MD): -1.44 days (95% CI -3.79 to 0.91)) but did in cohort studies (MD: -1.52 days (95% CI -2.71 to -0.34)). No statistically significant benefit of lighter sedation was identified in RCTs. In cohort studies, lighter sedation improved time to extubation, intensive care and hospital length of stay and ventilator-associated pneumonia. We found no significant effects for hospital mortality, delirium or adverse events. CONCLUSION: Evidence of benefit from lighter sedation is limited, with inconsistency between observational and randomised studies. Positive effects were mainly limited to low quality evidence from observational studies, which could be attributable to bias and confounding factors.

Gastric emptying in health and type 2 diabetes: An evaluation using a 75 g oral glucose drink.

AIM: Gastric emptying is a major determinant of the glycaemic response to carbohydrate and is frequently abnormal in type 2 diabetes (T2DM). There is little information about how chronic glycaemic control affects gastric emptying in T2DM. We evaluated gastric emptying of a 75 g glucose drink in community-based patients with T2DM of short duration with good or poor glycaemic control, and compared this to young and older controls. METHODS: T2DM patients managed by diet and/or metformin, either well-controlled or poorly-controlled, together with young and age-matched older controls without diabetes, consumed a 75 g oral glucose drink containing 150 mg 13C-acetate for evaluation of gastric emptying (breath test) and blood glucose over 180 min. RESULTS: The gastric half-emptying time (T50) was longer in the older than the young non-diabetic subjects (P = 0.041), but shorter in well-controlled T2DM patients than age-matched older controls (P = 0.043). The T50 in poorly-controlled T2DM patients was shorter than in older controls (P = 0.006), but similar to young non-diabetic subjects. CONCLUSIONS: Gastric emptying of a glucose drink is delayed with ageing, but more rapid in patients with T2DM of relatively short duration, regardless of their glycaemic status. These observations support interventions that slow gastric emptying to improve postprandial glycaemia in these patients with T2DM.

The use of altered rapid response calling criteria in a tertiary referral facility.

PURPOSE: The purpose of this study was to examine the current utilisation of altered rapid response calling criteria (ARRCCs) at a tertiary hospital. METHODS: A retrospective review of all acute care admissions across 17 months was undertaken using the hospital administration system and electronic medical record to identify patients with ARRCCs. In patients with altered criteria, the type of alteration, frequency of rapid response calls, cardiac arrest, intensive care admission, and death in the hospital were identified. Comparisons were made using standard statistical methods. RESULTS: The total hospital admissions numbered 45 912, with ARRCCs used in 768 (1.7%). Patients with an ARRCC during hospital admission were older (68.5 [55.5, 79.0] vs 59.0 [43.0, 72.0] years, p < 0.001) and had a significantly longer length of hospital stay (6.9 [3.0, 16.3] vs 2 [1, 5] days, p < 0.001).Compared with the total group of patient admissions, patients with ARRCCs more frequently triggered a rapid response team (9.0% vs 14.2%, χ2(1, n = 46 680) = 23.87, p < 0.001), more frequently suffered a cardiac arrest (0.2 vs 0.9%, χ2(1, n = 46 678) = 20.34, p < 0.001), more frequently died in the hospital (p < 0.001), and were less frequently discharged home (χ2(1, n = 46 680) = 43.91, p < 0.001). CONCLUSION: Patients with an ARRCC stayed longer in the hospital and were at increased risk of cardiac arrest and death during hospitalisation. Further exploration of the role of ARRCCs in facilitating individualised care to meet the needs and treatment goals of each patient in the acute hospital setting is required.

Acute Effects of Lixisenatide on Energy Intake in Healthy Subjects and Patients with Type 2 Diabetes: Relationship to Gastric Emptying and Intragastric Distribution.

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal (p < 0.001) and distal (p < 0.001) stomach and decreased EI (p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo (r = -0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

Longitudinal Changes in the Blood Pressure Responses to, and Gastric Emptying of, an Oral Glucose Load in Healthy Older Subjects.

The rate of gastric emptying is a major determinant of the hypotensive response to a meal. Cross-sectional studies suggest that healthy aging is associated with a modest slowing of gastric emptying. We aimed to determine longitudinal changes in the blood pressure (BP) response to, and gastric emptying of, glucose in healthy older people. Thirty-three participants (77.0 ± 0.7 years) had baseline and follow-up measurements after 5.8 ± 0.1 years. Participants consumed a 300-mL drink containing 75 g glucose and 150 mg C13-acetate. BP and heart rate (HR) were measured at 5-minute intervals for 120 minutes after the drink. Exhaled breath was collected to calculate the gastric 50% emptying time. The prevalence of postprandial hypotension (PPH) doubled from 9.1% to 18.2%. Gastric emptying was slower at follow-up (p = .04). The fall in systolic BP (SBP) was related directly to the rate of gastric emptying at both the initial study (r = .54, p = .005) and at follow-up (r = .41, p = .04). The change in the maximum fall in SBP was related to the increase in baseline SBP (r = -.63, p < .001). In conclusion, in healthy older people over a period of ~5.8 years, there was an increased prevalence of PPH and a modest slowing of gastric emptying. The latter was related directly to a greater hypotensive response.

The relationship between plasma GIP and GLP-1 levels in individuals with normal and impaired glucose tolerance.

AIMS: Glucose-dependent insulinotropic polypeptide (GIP) is released primarily from the proximal small intestine and glucagon-like peptide-1 (GLP-1) from the more distal small intestine and colon. Their relative importance to the incretin effect in health has been contentious in the past, although it now appears that GIP has the dominant role. It is uncertain whether there is a relationship between GIP and GLP-1 secretion. We aimed to evaluate the relationship between plasma GIP and GLP-1 responses to a 75-g oral glucose load in individuals with normal (NGT) and impaired glucose tolerance (IGT). METHODS: One hundred healthy subjects had measurements of blood glucose, serum insulin, plasma GIP and GLP-1 concentrations for 240 min after a 300 mL drink containing 75 g glucose. RESULTS: Fifty had NGT and 41 IGT; 9 had type 2 diabetes and were excluded from analysis. In both groups, there were increases in plasma GIP and GLP-1 following the glucose drink, with no difference in the magnitude of the responses between t = 0-240 min. There was a weak relationship between the iAUC0-240 min for GIP and GLP-1 in the combined (r = 0.23, P = 0.015) and in the IGT (r = 0.34, P = 0.01), but not in the NGT (r = 0.15, P = 0.14) group. CONCLUSIONS: There is a weak relationship between oral glucose-induced GIP and GLP-1 secretions in non-diabetic subjects.

A randomized, crossover study of the acute effects of acarbose and gastric distension, alone and combined, on postprandial blood pressure in healthy older adults.

BACKGROUND: Postprandial hypotension (PPH) occurs frequently in the elderly and patients with type 2 diabetes, and lacks a satisfactory treatment. Gastric distension and the α-glucosidase inhibitor, acarbose, may attenuate the postprandial fall in blood pressure (BP) by complementary mechanisms. We aimed to determine whether gastric distension and acarbose have additive effects to attenuate the fall in BP induced by oral sucrose. METHODS: Ten healthy older adults (74.0 ± 1.4 yr) had measurements of BP and superior mesenteric artery (SMA) blood flow for 120 min after receiving either (i) the 'study drink' of 100 g sucrose in 300 mL of water (control treatment), (ii) a 300 mL water 'preload' 15 min before the 'study drink' (distension treatment), (iii) 100 mg acarbose dissolved in the 'study drink' (acarbose treatment) or (iv) a 300 ml water 'preload' 15 min before 100 mg acarbose dissolved in the 'study drink' (acarbose and distension treatment). RESULTS: The area under the curve (AUC)0-120min for mean arterial pressure (MAP) was greater (P = 0.005) and the maximum fall in MAP was less (P = 0.006) during treatments with acarbose. Gastric distension did not affect the MAP-AUC0-120min response to acarbose (P = 0.44) and there was no effect of gastric distension alone (P = 0.68). Both acarbose treatments attenuated the rise in SMA blood flow (P = 0.003), whereas gastric distension had no effect. CONCLUSIONS: In healthy older adults, acarbose (100 mg), but not gastric distension, attenuates the fall in BP and rise in SMA blood flow after oral sucrose. The observations support the use of acarbose, but not gastric distension, to attenuate a postprandial fall in BP. TRIAL REGISTRATION: The study was retrospectively registered at ( ACTRN12618000152224 ) on February 02nd 2018.

Longitudinal Changes in Fasting and Glucose-Stimulated GLP-1 and GIP in Healthy Older Subjects.

CONTEXT: It is not known whether glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels correlate within individuals, nor whether levels change with age. Previous studies have all been cross-sectional in design. OBJECTIVE: To evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects. PATIENTS AND DESIGN: Forty-one healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75-g oral glucose load on two occasions separated by 5.9 ± 0.1 years [mean age at the initial study: 71.2 ± 3.8 (SD) years]. Breath samples were collected to calculate the gastric 50% emptying time (T50). RESULTS: For GLP-1, both fasting concentrations (P < 0.001) and area under the curve 0 to 120 minutes (P = 0.001) were decreased at followup. Fasting GIP was also lower (P = 0.03) at follow up, but there was no change in the area under the curve 0 to 120 minutes (P = 0.26). The gastric emptying T50 was slower at followup (P = 0.008). Neither the change in T50 nor the body mass index at the initial study was a determinant of the change in incretin responses. Between the two study days, fasting GIP (r = 0.72, P < 0.001) correlated well, but not fasting GLP-1 (r = 0.23, P = 0.18). However, both glucose-stimulated GLP-1 (r = 0.50, P = 0.002) and GIP (r = 0.60, P < 0.001) showed correlations between the initial and follow-up studies. CONCLUSIONS: Fasting GIP and glucose-stimulated GLP-1 and GIP concentrations correlate within individuals over a follow-up period of ∼5.9 years. Aging is associated with reductions in fasting GLP-1 and GIP, and glucose-stimulated GLP-1, which may predispose to the development of glucose intolerance and type 2 diabetes.

Effects of lixisenatide on postprandial blood pressure, gastric emptying and glycaemia in healthy people and people with type 2 diabetes.

AIM: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM). MATERIALS AND METHODS: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 µg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink. RESULTS: Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001). CONCLUSIONS: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension.

Effects of Glutamine on Gastric Emptying of Low- and High-Nutrient Drinks in Healthy Young Subjects-Impact on Glycaemia.

Glutamine is a potent stimulus for the release of glucagon-like peptide-1, which increases postprandial insulin and slows gastric emptying (GE). We determined the effects of glutamine on GE of, and glycaemic responses to, low- and high-nutrient drinks in eight healthy males (mean age 21.6 ± 0.7 years and BMI 22.9 ± 0.7 kg/m²). Participants were studied on four occasions on which they consumed either a low-nutrient (beef soup; 18 kcal) or high-nutrient (75 g dextrose; 255 kcal) drink, each with or without 30 g of glutamine (120 kcal), in a randomised, crossover design. GE (2D ultrasound), blood glucose and plasma insulin concentrations were measured concurrently. Glutamine slowed GE (half emptying time (T50)) of both low- (45 ± 3 min vs. 26 ± 2 min, p < 0.001), and high-nutrient, (100 ± 5 min vs. 77 ± 5 min, p = 0.03) drinks, however, there was no effect on GE of the high nutrient drinks when expressed as kcal/min (3.39 ± 0.21 kcal/min vs. 3.81 ± 0.20 kcal/min, p = 0.25). There was no change in blood glucose after the low-nutrient drinks with or without glutamine, despite a slight increase in plasma insulin with glutamine (p = 0.007). The rise in blood glucose following the high-nutrient drink (p = 0.0001) was attenuated during the first 60 min by glutamine (p = 0.007). We conclude that in healthy subjects, glutamine slows GE of both low- and high-nutrient drinks comparably and attenuates the rise in blood glucose after the high-nutrient glucose drink.

Comparative effects of small intestinal glucose on blood pressure, heart rate, and noradrenaline responses in obese and healthy subjects.

Meal consumption leads to an increase in sympathetic output to compensate for hemodynamic changes and maintain blood pressure (BP). Obesity is associated with a blunting of the sympathetic response to meal ingestion, but interpretation of studies investigating these responses is compromised by their failure to account for the rate of gastric emptying, which is an important determinant of postprandial cardiovascular and sympathetic responses and, in both health and obesity, exhibits a wide interindividual variation. We sought to determine the effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP, heart rate (HR), and noradrenaline responses in obese and healthy control subjects. 12 obese subjects (age 36.6 ± 3.9 years, body mass index (BMI) 36.1 ± 1.3 kg/m2 ) and 23 controls (age 27.8 ± 2.4 years, BMI 22.4 ± 0.5 kg/m2 ) received intraduodenal infusions of glucose at 1 or 3 kcal/min, or saline, for 60 min (t = 0-60 min), followed by intraduodenal saline (t = 60-120 min). BP and HR were measured with an automatic cuff, and blood samples collected for measurement of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with a fall in diastolic BP in the control subjects only (P < 0.01), with no change in systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01), with no difference in responses between the groups. We conclude that cardiovascular and sympathetic responses to intraduodenal glucose infusion are comparable between obese and control subjects, and dependent on the rate of glucose delivery.

Effects of randomized whey-protein loads on energy intake, appetite, gastric emptying, and plasma gut-hormone concentrations in older men and women.

Background: Protein- and energy-rich supplements are used widely for the management of malnutrition in the elderly. Information about the effects of protein on energy intake and related gastrointestinal mechanisms and whether these differ between men and women is limited.Objective: We determined the effects of whey protein on energy intake, appetite, gastric emptying, and gut hormones in healthy older men and women.Design: Eight older women and 8 older men [mean ± SEM age: 72 ± 1 y; body mass index (in kg/m2): 25 ± 1] were studied on 3 occasions in which they received protein loads of 30 g (120 kcal) or 70 g (280 kcal) or a flavored water control drink (0 kcal). At regular intervals over 180 min, appetite (visual analog scales), gastric emptying (3-dimensional ultrasonography), and blood glucose and plasma gut-hormone concentrations [insulin, glucagon, ghrelin, cholecystokinin, gastric inhibitory polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and peptide tyrosine tyrosine (PYY)] were measured, and ad libitum energy intake was quantified from a buffet meal (180-210 min; energy intake, appetite, and gastric emptying in the men have been published previously).Results: Energy intake at the buffet meal was ∼80% higher in older men than in older women (P < 0.001). Energy intake was not suppressed by protein compared with the control in men or women (P > 0.05). There was no effect of sex on gastric emptying, appetite, gastrointestinal symptoms, glucose, or gut hormones (P > 0.05). There was a protein load-dependent slowing of gastric emptying, an increase in concentrations of insulin, glucagon, cholecystokinin, GIP, GLP-1, and PYY, and an increase in total energy intake (drink plus meal: 12% increase with 30 g and 32% increase with 70 g; P < 0.001). Energy intake at the buffet meal was inversely related to the stomach volume and area under the curve of hormone concentrations (P < 0.05).Conclusion: In older men and women, whey-protein drinks load-dependently slow gastric emptying and alter gut hormone secretion compared with a control but have no suppressive effect on subsequent ad libitum energy intake. This trial was registered at www.anzctr.org.au as ACTRN12612000941864.

Comparative effects of glucose and water drinks on blood pressure and cardiac function in older subjects with and without postprandial hypotension.

Postprandial hypotension (PPH) occurs frequently and is thought to reflect an inadequate increase in cardiac output to compensate for the rise in splanchnic blood flow after a meal. Gastric distension by water attenuates the postprandial fall in blood pressure (BP). Cardiac hemodynamics (stroke volume (SV), cardiac output (CO), and global longitudinal strain (GLS)) have hitherto not been measured in PPH We sought to determine the comparative effects of water and glucose drinks on cardiac hemodynamics in healthy older subjects and individuals with PPH Eight healthy older subjects (age 71.0 ± 1.7 years) and eight subjects with PPH (age 75.5 ± 1.0 years) consumed a 300 mL drink of either water or 75 g glucose (including 150 mg 13C-acetate) in randomized order. BP and heart rate (HR) were measured using an automatic device, SV, CO, and GLS by transthoracic echocardiography and gastric emptying by measurement of 13CO2 In both groups, glucose decreased systolic BP (P < 0.001) and increased HR, SV, and CO (P < 0.05 for all). The fall in systolic BP was greater (P < 0.05), and increase in HR less (P < 0.05), in the PPH group, with no difference in SV or CO Water increased systolic BP (P < 0.05) in subjects with PPH and, in both groups, decreased HR (P < 0.05) without affecting SV, CO, or GLS In subjects with PPH, the hypotensive response to glucose and the pressor response to water were related (R = -0.75, P < 0.05). These observations indicate that, in PPH, the hypotensive response to oral glucose is associated with inadequate compensatory increases in CO and HR, whereas the pressor response to water ingestion is maintained and, possibly, exaggerated.