Explore the vast range of titles available.

The true prevalence, however, remains uncertain because of a lack of population-based studies and inconsistent criteria to define gastroparesis, including variations in the technique used to quantify gastric emptying (where scintigraphy remains the gold standard method and stable isotope breath tests and ultrasonography represent acceptable alternatives), the desirable blood glucose levels during the emptying measurement, the magnitude of the delay in gastric emptying regarded as abnormal, and whether the presence of gastrointestinal symptoms represents a prerequisite for the diagnosis. [...]in an individual type 2 diabetic patient, the impact of a GLP-1 agonist on postprandial glycemia is likely to be dependent on both the baseline rate of emptying and the choice of GLP-1 agonist.

Gastric emptying is a major determinant of postprandial blood glucose, accounting for ~35% of variance in peak glucose in both healthy individuals and those with type 2 diabetes. Gastric emptying is frequently disordered in individuals with diabetes (both abnormally delayed and accelerated). Delayed gastric emptying, i.e. diabetic gastroparesis, may be linked to upper gastrointestinal symptoms for which current treatment remains suboptimal; pharmacological acceleration of delayed emptying is only weakly associated with symptom improvement. Accordingly, the relationship between symptoms and delayed gastric emptying is not simply ‘cause and effect’. In insulin-treated patients, disordered gastric emptying, even when not associated with gastrointestinal symptoms, can cause a mismatch between the onset of insulin action and the availability of absorbed carbohydrate, leading to suboptimal glycaemic control. In patients with type 2 diabetes, interventions that slow gastric emptying, e.g. glucagon-like peptide-1 receptor agonists, reduce postprandial blood glucose. This review focuses on recent insights into the impact of gastric emptying on postprandial blood glucose, effects of diabetes therapy on gastric emptying and the management of disordered gastric emptying in diabetes. In view of the broad relevance of gastric emptying to diabetes management, it is important that future clinical trials evaluating novel therapies that may affect gastric emptying should quantify the latter with an appropriate technique, such as scintigraphy or a stable isotope breath test.

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), which are released from the intestines after meals, are responsible for augmenting insulin secretion (ie, the incretin effect). Because the insulinotropic effect of GIP is markedly attenuated in type 2 diabetes, therapeutic development to date has focused on GLP-1, which also lowers blood glucose by suppressing glucagon and energy intake, and slowing gastric emptying.1 Use of GLP-1 receptor agonists for the management of type 2 diabetes is increasing rapidly, and is associated with weight loss, negligible risk of hypoglycaemia, and potential cardiovascular protection. [...]how much does GIP receptor stimulation contribute to the effects of tirzepatide? GIP has incompletely understood effects on adipose tissue, intestinal blood flow, glucagon secretion, and even bone resorption; moreover, its insulinotropic effect can be restored, in part, with fastidious glycaemic control.8 Historically, the evaluation of GIP actions has been hampered by species differences, but a human GIP receptor antagonist is now available, and should be used in future mechanistic studies.9 Second, does persistent slowing of gastric emptying by GLP-1 receptor stimulation contribute to the substantial reductions in postprandial glycaemia by tirzepatide? [...]the positioning of tirzepatide in the therapeutic algorithm will be influenced by emerging information on cardiovascular outcomes, fatty liver disease, renal protection, and durability of effects, which is awaited with interest.

Abstract 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 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.

Anxiety disorders are common, complex psychiatric disorders with twin heritabilities of 30–60%. We conducted a genome-wide association study of Lifetime Anxiety Disorder (ncase = 25 453, ncontrol = 58 113) and an additional analysis of Current Anxiety Symptoms (ncase = 19 012, ncontrol = 58 113). The liability scale common variant heritability estimate for Lifetime Anxiety Disorder was 26%, and for Current Anxiety Symptoms was 31%. Five novel genome-wide significant loci were identified including an intergenic region on chromosome 9 that has previously been associated with neuroticism, and a locus overlapping the BDNF receptor gene, NTRK2. Anxiety showed significant positive genetic correlations with depression and insomnia as well as coronary artery disease, mirroring findings from epidemiological studies. We conclude that common genetic variation accounts for a substantive proportion of the genetic architecture underlying anxiety.

Abstract Context Gastric emptying is a major determinant of postprandial glycemia and is often delayed in long-standing, complicated type 2 diabetes mellitus (T2DM). However, there is little information about gastric emptying in well-controlled T2DM. Objective To evaluate the rate of gastric emptying in community-based patients with relatively well-controlled T2DM compared with young and older control subjects without diabetes. Participants and Design A total of 111 patients with T2DM managed by diet (n = 52) or metformin monotherapy (n = 59) (HbA1c 6.6 ± 0.1%/49.0 ± 0.9 mmol/mol), 18 age- and body mass index (BMI)-matched older subjects without diabetes, and 15 young healthy subjects consumed a standardized mashed potato meal (368.5 kcal) containing 100 μL 13C-octanoic acid. Gastric emptying (by breath test) and blood glucose were evaluated over 240 minutes. Results Gastric emptying was slower in the older than in the young subjects without diabetes (2.3 ± 0.1 vs 3.0 ± 0.1 kcal/min, P = 0.0008). However, relative to the age- and BMI-matched subjects without diabetes, gastric emptying (2.8 ± 0.1 kcal/min) was faster in patients with T2DM (P = 0.0005). Furthermore, gastric emptying was faster in the metformin-treated (3.0 ± 0.1 kcal/min) than in the diet-controlled (2.7 ± 0.1 kcal/min) patients with T2DM (P = 0.011), although there were no differences in age, BMI, HbA1c, or the duration of known diabetes. The increments in blood glucose (at t = 30 and 60 minutes and the incremental area under the curve during t = 0 to 120 minutes) after the meal were related directly to the rate of gastric emptying in the subjects with T2DM regardless of treatment with or without metformin (P < 0.05 each). Conclusions Gastric emptying is slowed with aging but otherwise is relatively more rapid in patients with well-controlled T2DM. This provides a strong rationale for slowing gastric emptying to improve postprandial glycemic control in these patients. Gastric emptying is slowed with aging but otherwise more rapid in relatively well-controlled T2DM patients, in whom the postprandial blood glucose excursion is related to gastric emptying.