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Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual GLP-1- and glucose-dependent insulinotropic polypeptide receptor co-agonist tirzepatide (referred to here collectively as "GLP-1-based therapy") are incretin-based therapies being used increasingly in the management of both type 2 diabetes and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (eg, hypoglycemia in individuals on insulin or sulphonylurea therapy). Their effects on the gallbladder may also be beneficial, contributing to reducing postprandial triglycerides, but they also potentially increase the risk of biliary disease. In this review, we summarize the effects of GLP-1 and incretin-based therapeutics on gastric, biliary and small intestinal function. An improved understanding of these effects will optimize the use of these drugs. [ABSTRACT FROM AUTHOR]

Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction. Data Acquisition We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. Data Synthesis Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. Conclusion Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs. [ABSTRACT FROM AUTHOR]

Background: The herbal preparation, STW5‐II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5‐II on esophago‐gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut–brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. Methods: STW5‐II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double‐blind, randomized fashion, on two separate occasions, separated by 3–7 days, to evaluate effects on (i) esophago‐gastric junction pressures following a standardized meal using solid‐state high‐resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high‐resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). Key Results: STW5‐II increased maximum intrabag volume (ml; STW5‐II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago‐gastric junction, pyloric, or duodenal pressures. Conclusions & Inferences: STW5‐II has marked region‐specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia. [ABSTRACT FROM AUTHOR]

Aim: To perform a direct, double‐blind, randomised, crossover comparison of subcutaneous and intravenous glucagon‐like peptide‐1 (GLP‐1) in hyperglycaemic subjects with type 2 diabetes naïve to GLP‐1‐based therapy. Materials and Methods: Ten fasted, hyperglycaemic subjects (1 female, age 63 ± 10 years [mean ± SD], glycated haemoglobin 73.5 ± 22.0 mmol/mol [8.9% ± 2.0%], both mean ± SD) received subcutaneous GLP‐1 and intravenous saline, or intravenous GLP‐1 and subcutaneous saline. Infusion rates were doubled every 120 min (1.2, 2.4, 4.8 and 9.6 pmol·kg−1·min−1 for subcutaneous, and 0.3, 0.6, 1.2 and 2.4 pmol·kg−1·min−1 for intravenous). Plasma glucose, total and intact GLP‐1, insulin, C‐peptide, glucagon and gastrointestinal symptoms were evaluated over 8 h. The results are presented as mean ± SEM. Results: Plasma glucose decreased more with intravenous (by ~8.0 mmol/L [144 mg/dL]) than subcutaneous GLP‐1 (by ~5.6 mmol/L [100 mg/dL]; p < 0.001). Plasma GLP‐1 increased dose‐dependently, but more with intravenous than subcutaneous for both total (∆max 154.2 ± 3.9 pmol/L vs. 85.1 ± 3.8 pmol/L; p < 0.001), and intact GLP‐1 (∆max 44.2 ± 2.2 pmol/L vs. 12.8 ± 2.2 pmol/L; p < 0.001). Total and intact GLP‐1 clearance was higher for subcutaneous than intravenous GLP‐1 (p < 0.001 and p = 0.002, respectively). The increase in insulin secretion was greater, and glucagon was suppressed more with intravenous GLP‐1 (p < 0.05 each). Gastrointestinal symptoms did not differ (p > 0.05 each). Conclusions: Subcutaneous GLP‐1 administration is much less efficient than intravenous GLP‐1 in lowering fasting plasma glucose, with less stimulation of insulin and suppression of glucagon, and much less bioavailability, even at fourfold higher infusion rates. [ABSTRACT FROM AUTHOR]

Aim: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). Methods: In cohort 1, 70 newly diagnosed, treatment‐naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75‐g glucose drink containing 150 mg 13C‐acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi‐solid mashed potato meal, labelled with 100 μl 13C‐octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). Results: Gastric emptying was slower in female than male subjects in both cohorts (both p <.01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p <.05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p <.001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p <.05). Conclusions: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume‐adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D. [ABSTRACT FROM AUTHOR]

Aim: To evaluate gastric emptying (GE) and the glycaemic response to a 75‐g oral glucose load in newly diagnosed, treatment‐naïve Han Chinese with type 2 diabetes (T2D) before insulin pump therapy, after 4 weeks of insulin pump therapy, and 12–15 months after insulin pump therapy. Materials and Methods: Twenty participants with T2D (baseline glycated haemoglobin [± SD] 10.7% [± 1.2%] 93 [± 10] mmol/mol) ingested a 75‐g glucose drink containing 150 mg 13C‐acetate, to determine the gastric half‐emptying time, and underwent assessment of plasma glucose and serum insulin, C‐peptide and glucagon‐like peptide‐1 (GLP‐1) over 180 min before and after 4 weeks of insulin pump therapy (discontinued for 48 h before re‐assessment). Data were compared to those in 19 healthy participants matched for sex and age. After 12–15 months, GE was re‐measured in 14 of the T2D participants. Results: At baseline, participants with T2D exhibited substantially augmented fasting and post‐glucose glycaemia, diminished insulin secretion, and more rapid GE (p < 0.05 each), but comparable GLP‐1, compared to healthy participants. Following insulin pump therapy, insulin secretion increased, GLP‐1 secretion was attenuated, fasting and post‐glucose glycaemia were lower, and GE was slowed (p < 0.05 each). The slowing of GE in T2D participants was sustained over 12–15 months of follow‐up. Conclusions: In newly diagnosed Han Chinese with T2D, GE is often accelerated despite poor glycaemic control and is slowed by short‐term insulin pump therapy. The effect on GE is maintained for at least 12 months. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Metformin lowers postprandial glycaemic excursions in individuals with type 2 diabetes by modulating gastrointestinal function, including the stimulation of glucagon-like peptide-1 (GLP-1). The impact of varying the timing of metformin administration on postprandial glucose metabolism is poorly defined. We evaluated the effects of metformin, administered at different intervals before an intraduodenal glucose infusion, on the subsequent glycaemic, insulinaemic and GLP-1 responses in metformin-treated type 2 diabetes. Methods: Sixteen participants with type 2 diabetes that was relatively well-controlled by metformin monotherapy were studied on four separate days in a crossover design. On each day, participants were randomised to receive a bolus infusion of metformin (1000 mg in 50 ml 0.9% saline) via a nasoduodenal catheter at t = −60, −30 or 0 min (and saline at the other timepoints) or saline at all timepoints (control), followed by an intraduodenal glucose infusion of 12.56 kJ/min (3 kcal/min) at t = 0–60 min. The treatments were blinded to both participants and investigators involved in the study procedures. Plasma glucose, insulin and total GLP-1 levels were measured every 30 min between t = −60 min and t = 120 min. Results: There was a treatment-by-time interaction for metformin in reducing plasma glucose levels and increasing plasma GLP-1 and insulin levels (p<0.05 for each). The reduction in plasma glucose levels was greater when metformin was administered at t = −60 or −30 min vs t = 0 min (p<0.05 for each), and the increases in plasma GLP-1 levels were evident only when metformin was administered at t = −60 or −30 min (p<0.05 for each). Although metformin did not influence insulin sensitivity, it enhanced glucose-induced insulin secretion (p<0.05), and the increases in plasma insulin levels were comparable on the 3 days when metformin was given. Conclusions/interpretation: In well-controlled metformin-treated type 2 diabetes, glucose-lowering by metformin is greater when it is given before, rather than with, enteral glucose, and this is associated with a greater GLP-1 response. These observations suggest that administration of metformin before meals may optimise its effect in improving postprandial glycaemic control. Trial registration: www.anzctr.org.au ACTRN12621000878875 Funding: The study was not funded by a specific research grant. [ABSTRACT FROM AUTHOR]

A study published in the American Journal of Physiology: Gastrointestinal & Liver Physiology examines the potential impact of the menstrual cycle on gastric myoelectrical activity in healthy humans. The study introduces a new technique called "body surface gastric mapping" (BSGM), which is an improved version of the traditional electrogastrography (EGG) method. The researchers found that the principal frequency of gastric slow waves is higher in the luteal phase compared to the follicular phase in premenopausal women. However, the clinical relevance of this finding and the mechanisms behind it remain unclear. The study highlights the need for further research and caution in interpreting the results. [Extracted from the article]

The article discusses the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on blood pressure. GLP-1 receptor agonists have been shown to have cardiovascular and renal protective effects, independent of their glucose-lowering properties. While these drugs have been found to reduce systolic blood pressure in hypertensive individuals, they have little effect on diastolic blood pressure or normotensive individuals. The article also highlights the importance of accurately measuring blood pressure, including postprandial blood pressure, and suggests that further research is needed to optimize the assessment of the effects of GLP-1 receptor agonists on blood pressure. [Extracted from the article]

Background: Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. Methods: Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. Results: Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = −0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = −0.34, P = 0.012) and dinner (r = −0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. Conclusions: In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article explores the relationship between outdoor sports and the age of empire on the American frontier using the lens of gender performance. Focused on the years from the mid to the late nineteenth century, it provides an exploration of hunting as a vector of imperial masculine journey and a physical and imaginative pursuit where hunters stalked and shot the iconic animals of the western states on behalf of settler colonialism. In the first part of the paper, contemporary testimonies are used to plot the ways in which hunting desires to own the animal body fuelled a powerful homosocial culture grounded in ideas of primal pageantry. Sport and game in this context represented essential elements of a performative leisure economy in which pursuit and capture dictated the terms of human-animal engagement and refracted broader impositions of colonial political authority. From here, it turns to dynamics of community on the game trail where the primacy of the sporting hero was confirmed and recalibrated along racial, class and gender lines, before travelling indoors to examine how the afterlife of the hunt (expressed in taxidermy) allowed the authority of the victorious hunter to be performed in the 'great indoors' and for colonial claims over space to be materially and symbolically affirmed. Today, the stories of the imperial hunter elite and their taxidermy trophies represent traumatic historical artefacts. However, they also denote important remnants of empire whose complicated provenance helps to explain how mutually supportive mechanisms of masculinity and colonialism operated to sanction the killing and (later) the conservation of game species. Offering a closer look at 'the bison in the room' and its embodied story of pursuit and capture, this paper provides valuable insights into the dynamics of sport in colonial space and the value of performance as a useful category for contextualising human-environmental relations in the age of empire. [ABSTRACT FROM AUTHOR]

Justified trust is rationally permitted trust; wise trust is excellent trust. Excellent (dis)trust is always justified (dis)trust, but the reverse is not true. You can be justified in distrusting someone and yet it be wise for you to trust. Contrary to folk saying, wisdom does not favour distrust ahead of trust. This paper explores what it takes to be wise in entering, maintaining, modifying and exiting trust relations. Wisdom is socially scaffolded, including by distributed networks of distrust that make local trust wise. [ABSTRACT FROM AUTHOR]

Addressing a paucity of large‐scale studies about women academics maternity experiences of leave in academia and under‐theorizing the influence of neoliberalism on this phenomenon, this research provides one of the largest studies of women's experiences of maternity leave in the academic sector. Secondary analysis of a subset of data from a global online mixed method survey with 553 women academics (82% UK, 18% international) was undertaken to explore experiences and implications of maternity leave for women. The findings reveal that women academics continued to undertake core academic work duties during maternity leave such as writing grant applications and journal articles, supervising doctoral students, teaching, and responding to emails. We document four distinct orientations adopted by women during maternity leave that characterize neoliberal subjectivity and use Foucauldian governmentality to unmask the inculcation of such norms. Our analysis shows how neoliberal ideology has gained a hegemonic position in academia that leaves little space for maternity leave, resulting in many women effectively relinquishing their maternity rights to sustain academic productivity. We argue that neoliberalism and new managerialism within the academy undermine policies to support women's maternity rights. The findings of this study will be of interest to scholars and Human Resources professionals, academic mothers, managers, and policymakers who are championing change in the sector. [ABSTRACT FROM AUTHOR]

Background and aims: Bariatric surgery is the most effective treatment in individuals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in individuals with and without post-bariatric surgery hypoglycaemia have not been systematically examined. Materials and methods: The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated individuals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA1c) was also evaluated. A random-effects meta-analysis was performed, and Hedges' g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ2 estimate and I2 statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias. Results: From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing individuals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA1c was less in individuals with hypoglycaemia − 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ2 = 0.2, I2 = 54.3. No publication bias was evident. Conclusion: Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in individuals with post-bariatric surgery hypoglycaemia, while HbA1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of individuals with hypoglycaemia following RYGB. PROSPERO Registration Number: CRD42021287515. [ABSTRACT FROM AUTHOR]

Seizure liability remains a significant cause of attrition throughout drug development. Advances in stem cell biology coupled with an increased understanding of the role of ion channels in seizure offer an opportunity for a new paradigm in screening. We assessed the activity of 15 pro-seizurogenic compounds (7 CNS active therapies, 4 GABA receptor antagonists, and 4 other reported seizurogenic compounds) using automated electrophysiology against a panel of 14 ion channels (Nav1.1, Nav1.2, Nav1.6, Kv7.2/7.3, Kv7.3/7.5, Kv1.1, Kv4.2, KCa4.1, Kv2.1, Kv3.1, KCa1.1, GABA α1β2γ2, nicotinic α4β2, NMDA 1/2A). These were selected based on linkage to seizure in genetic/pharmacological studies. Fourteen compounds demonstrated at least one "hit" against the seizure panel and 11 compounds inhibited 2 or more ion channels. Next, we assessed the impact of the 15 compounds on electrical signaling using human-induced pluripotent stem cell neurons in microelectrode array (MEA). The CNS active therapies (amoxapine, bupropion, chlorpromazine, clozapine, diphenhydramine, paroxetine, quetiapine) all caused characteristic changes to electrical activity in key parameters indicative of seizure such as network burst frequency and duration. The GABA antagonist picrotoxin increased all parameters, but the antibiotics amoxicillin and enoxacin only showed minimal changes. Acetaminophen, included as a negative control, caused no changes in any of the parameters assessed. Overall, pro-seizurogenic compounds showed a distinct fingerprint in the ion channel/MEA panel. These studies highlight the potential utility of an integrated in vitro approach for early seizure prediction to provide mechanistic information and to support optimal drug design in early development, saving time and resources. [ABSTRACT FROM AUTHOR]

Against a background of Bologna process goals to improve employment prospects for PhD graduates, and the crisis of precarious employment conditions and prospects afflicting postdoctoral researchers – hitherto postdocs, the OECD ([2021], "Reducing the Precarity of Academic Research Careers." In OECD Science, Technology and Industry Policy Papers. Paris: OECD Publishing,) called for research into postdoctoral careers and the precarity phenomenon. This paper responds by giving attention to career breaks as these represent a prevalent but under researched aspect of postdoc precarity in the contemporary academic labor market. Utilizing a substantial international mixed-method dataset with a sample of 950 postdocs, the study examined experiences and perceptions of the professional and personal implications of academic career breaks. Results reveal significant differences between males and females in key areas: maternity was the main reason for females' career breaks, and redundancy/end of contract for males. Females resumed employment more with the same employer and males with a different employer. Support surrounding career breaks was mixed, largely inadequate, but not associated with gender. Perceptions of career breaks differed significantly across groups of postdocs that previously experienced a career break, those on a career break, and postdocs that had never had a career break. The latter two groups perceived negative career outcomes and positive personal outcomes more than postdocs who had previously had a career break, however, significant gender differences indicate females were more negative about the personal implications of career breaks. Discussion of the findings concludes that under neoliberalism postdocs represent a growing lumpen proletariat, leading to recommendations for policy, practice and further research into gender, precarity and postdoctoral careers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity is a major challenge to health and social care systems around the world. There is limited research exploring the wider contextual determinants that are important to improving care for this cohort. In this study, we aimed to elicit and prioritise determinants of improved care in people with multiple conditions. Methods: A three-round online Delphi study was conducted in England with health and social care professionals, data scientists, researchers, people living with multimorbidity and their carers. Results: Our findings suggest a care system which is still predominantly single condition focused. 'Person-centred and holistic care' and 'coordinated and joined up care', were highly rated determinants in relation to improved care for multimorbidity. We further identified a range of non-medical determinants that are important to providing holistic care for this cohort. Conclusions: Further progress towards a holistic and patient-centred model is needed to ensure that care more effectively addresses the complex range of medical and non-medical needs of people living with multimorbidity. This requires a move from a single condition focused biomedical model to a person-based biopsychosocial approach, which has yet to be achieved. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the performance of machine learning algorithms for the prediction of discharge within 12 and 24 h to produce a measure of readiness for discharge after general surgery. Methods: Consecutive general surgery patients at two tertiary hospitals, over a 2‐year period, were included. Observation and laboratory parameter data were stratified into training, testing and validation datasets. Random forest, XGBoost and logistic regression models were evaluated. Each ward round note time was taken as a different event. Primary outcome was classification accuracy of the algorithmic model able to predict discharge within the next 12 h on the validation data set. Results: 42 572 ward round note timings were included from 8826 general surgery patients. Discharge occurred within 12 h for 8800 times (20.7%), and within 24 h for 9885 (23.2%). For predicting discharge within 12 h, model classification accuracies for derivation and validation data sets were: 0.84 and 0.85 random forest, 0.84 and 0.83 XGBoost, 0.80 and 0.81 logistic regression. For predicting discharge within 24 h, model classification accuracies for derivation and validation data sets were: 0.83 and 0.84 random forest, 0.82 and 0.81 XGBoost, 0.78 and 0.79 logistic regression. Algorithms generated a continuous number between 0 and 1 (or 0 and 100), representing readiness for discharge after general surgery. Conclusions: A derived artificial intelligence measure (the Adelaide Score) successfully predicts discharge within the next 12 and 24 h in general surgery patients. This may be useful for both treating teams and allied health staff within surgical systems. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: People with dementia living at home represent a growing group of social care services users in England. Many are unable to complete questionnaires due to cognitive impairment. The ASCOT-Proxy is an adapted version of an established measure, ASCOT, which was developed as a way of collecting social care-related quality of life (SCRQoL) data from this group of service users, either alone or alongside the ASCOT-Carer, a measure of SCRQoL for unpaid carers. The ASCOT-Proxy includes two perspectives, the proxy-proxy perspective ('My opinion: What I think') and proxy-person perspective ('What I think the person I represent thinks'). We aimed to establish the feasibility, construct validity and reliability of the ASCOT-Proxy and ASCOT-Carer, with unpaid carers of people with dementia living at home unable to self-report. We also aimed to establish structural characteristics of the ASCOT-Proxy. Methods: Cross-sectional data were collected using self-administered questionnaire (paper or online) among unpaid carers living in England between January 2020 and April 2021. Unpaid carers could take part if they supported someone living with dementia who was unable to self-complete a structured questionnaire. The person living with dementia or their unpaid carer had to use at least one social care service. We used the proportion of missing data to establish feasibility, ordinal exploratory factor analysis to establish structural characteristics, Zumbo's ordinal alpha for internal reliability, and hypothesis testing for construct validity. We also conducted Rasch analysis. Results: We analysed data for 313 carers (62.4(± 12.0) years, 75.7% (N=237) females). We were able to calculate the ASCOT-Proxy-proxy overall score for 90.7% of our sample, the ASCOT-Proxy-person overall score for 88.8% of our sample and in case of the ASCOT-Carer for 99.7% of our sample. As there was an issue with structural characteristics of the ASCOT-Proxy-proxy we conducted Rasch, reliability and construct validity analysis for the ASCOT-Proxy-person and ASCOT-Carer only. Conclusions: This was a first study to explore psychometric characteristics of the ASCOT-Proxy and ASCOT-Carer with unpaid carers of people with dementia living at home unable to self-report. There are some aspects of the psychometric characteristics of the ASCOT-Proxy and ASCOT-Carer that warrant further investigation in future. Trial registration NA [ABSTRACT FROM AUTHOR]

Aim: To investigate whether co‐ingestion of dietary protein with, or before, carbohydrate may be a useful strategy to reduce postprandial hyperglycaemia in older men with type 2 diabetes (T2D). Materials and Methods: Blood glucose, plasma insulin and glucagon concentrations were measured for 180 minutes following ingestion of a drink containing 30 g of glucose (G; 120 kcal), 30 g of whey protein (120 kcal), 30 g of glucose plus 30 g of whey protein (GP; 240 kcal), or control (~2 kcal) in older men with T2D (n = 10, 77 ± 1 years; 31 ± 1.7 kg/m2) and without T2D (n = 10, 78 ± 2 years; 27 ± 1.4 kg/m2). Mixed model analysis was used. Results: GP versus G markedly reduced the increase in blood glucose concentrations (P <.001) and had a synergistic effect on the increase in insulin concentrations (P <.001), in men both with and without T2D. Glucose concentrations were higher in men with T2D compared with those without T2D, whereas insulin and glucagon concentrations were largely unaffected by the presence of T2D. Gastric emptying was faster in men with T2D than in those without T2D. Conclusions: The ability of whey protein to reduce carbohydrate‐induced, postprandial hyperglycaemia is retained in older men with T2D compared with those without T2D, and whey protein supplementation may be a useful strategy in the prevention and management of T2D in older people. [ABSTRACT FROM AUTHOR]