Glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) or glucagon receptor agonists have emerged as promising agents to treat metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH). Although the beneficial effects of GLP-1RAs on glycemic control and weight are well-established, clinicians may be unfamiliar with other potential benefits of this class.

We examined the pleiotropic effects of GLP-1RAs and how they relate to gastroenterologists for MASLD/MASH treatment. Our narrative review of English articles included four GLP-1RAs (subcutaneous semaglutide, liraglutide, dulaglutide, and efpeglenatide), a dual GLP-1/GIP agonist (tirzepatide), a dual GLP-1/glucagon receptor agonist (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes and landscape.

In Phase I - III trials, GLP-1RAs are associated with clinically relevant hepatic improvements including MASH resolution, liver fat reduction, and preventing worsening fibrosis. Effects on cardiometabolic parameters align with type 2 diabetes/obesity Phase III data, comprising substantial improvements in glycemic, weight, and cardiovascular outcomes. Promising data also suggest benefits in common comorbidities, including obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.GLP-1RAs represent a valuable pharmacotherapeutic option for gastroenterologists managing individuals with MASLD/MASH and cardiometabolic comorbid conditions.

Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.

A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.

The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21-5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46-0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31-0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27-0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).

This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.

Obesity is associated with an increased risk of reflux esophagitis (RE). Metabolic abnormalities have been implicated in the pathogenesis of RE. However, the role of metabolic status in the risk of RE among individuals with varying degrees of obesity remains unclear. Therefore, our study aimed to assess the association between metabolic obesity phenotypes and the risk of RE.

This study included a cohort of 24,368 participants aged 18 years and older who underwent upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University during health checkups between January 1, 2008, and December 31, 2021. Among these participants, a total of 9,947 individuals were classified into four groups based on their obesity phenotype: metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO). To account for potential confounding factors, multivariate logistic regression analysis was applied to examine the association between metabolic obesity phenotypes and the risk of RE, with stratification by sex and age.

Among all participants, the MUNW, MHO, and MUO groups demonstrated a higher risk of RE when compared to the MHNW group. After controlling for all confounding factors, the MUO group exhibited the highest risk, with an odds ratio (OR) of 3.723 (95% CI: 2.751-5.040) in males and 5.482 (95% CI: 4.080-7.367) in females. The prevalence of RE increased in proportion to the number of metabolic risk factors. Subgroup analyses, which accounted for all confounders, revealed that the MHO, MUNW, and MUO phenotypes were associated with an elevated risk of RE in individuals under 60 years old as well as those over 60 years old. Interestingly, a more comprehensive analysis indicated that obesity may have a greater effect on the risk of RE than metabolic disorders.

Both metabolic disorders and obesity were associated with an increased risk of RE. The effect of obesity on RE prevalence may be stronger than that of metabolic disorders, emphasizing the significance of obesity regardless of metabolic health status. Clinical interventions should address not only obesity but also metabolic disorders in order to reduce the risk of RE.

The global prevalence of Metabolic Syndrome (MetS) is increasing, primarily characterized by abdominal obesity, which significantly heightens the risk of cardiovascular diseases, gastrointestinal disorders, and cancers. Constipation is a common gastrointestinal issue that impacts both physiological and psychological health and worsens with age. Calcium, an essential mineral vital for human health, has been proven to be crucial not only for bone health but also beneficial for gastrointestinal health. However, the results regarding its impact on constipation are inconsistent. This study aimed to investigate the relationship between dietary calcium intake and constipation in individuals with MetS.

This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. Participants were assessed for MetS based on the International Diabetes Federation (IDF) criteria. Dietary calcium intake was evaluated through 24-h dietary recalls, and constipation was defined based on the frequency of bowel movements recorded in the bowel health questionnaire. The relationship between calcium intake and constipation was explored using logistic regression models with adjustment for covariates, and restricted cubic spline analyses were also used to investigate nonlinear relationships.

The study included 4,838 adult participants with MetS. Adjusted logistic regression revealed that an increase in dietary calcium intake was significantly associated with a reduced risk of constipation (OR: 0.562, 95% CI: 0.379 to 0.835, p = 0.006). Compared to the lowest quartile, the highest quartile of dietary calcium intake significantly decreased the risk of constipation (OR: 0.282, 95% CI: 0.115 to 0.691, p = 0.008). Results from the restrictive cubic spline analysis indicated a negative linear association between dietary calcium intake and constipation risk (non-linearity p = 0.704).

The findings suggested that increased dietary calcium intake is associated with a decreased risk of constipation among MetS patients, emphasizing dietary calcium as a potentially modifiable factor for managing gastrointestinal symptoms in this population.

The relationship between the metabolically healthy obesity (MHO) phenotype and the occurrence of gastroesophageal reflux disease (GERD) and inefficient esophageal motility (IEM) is still unclear. Thus, we assessed the association between different metabolic obesity phenotypes and GERD and IEM using empirical data.

We collected clinical and test data of 712 patients, including 24-h multichannel intraluminal impedance-pH (24-h MII-pH) monitoring, high-resolution manometry (HRM), and endoscopy. We divided 567 individuals into four categories according to their metabolic obesity phenotype: metabolically unhealthy non-obesity (MUNO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHNO), and MHO. We compared differences in the 24-h MII-pH monitoring, HRM, and endoscopy findings among the four metabolic obesity phenotypes.

Patients with the MUNO, MHO, or MUO phenotype showed a greater risk of IEM and GERD (pathologic acid exposure time [AET] >6%) compared with patients with the MHNO phenotype. Regarding the HRM results, patients with the MHNO or MUNO phenotype had a lower integrated relaxation pressure, esophageal sphincter pressure, and esophagogastric junction contractile integral, and more ineffective swallows than patients with the MHO or MUO phenotype (p < 0.05). In terms of 24-h MII-pH, patients with the MHO or MUO phenotype had a higher total, upright, and supine AET; a higher total number of reflux episodes (TRs); and a lower mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index compared with those with the MHNO or MUNO phenotype (all p < 0.05). Considering the odds ratio of 19.086 (95% confidence interval 6.170-59.044) for pathologic AET and 3.659 (95% confidence interval 1.647-8.130) for IEM, patients with the MUO phenotype had the greatest risk after adjusting for all confounding variables.

Obesity and metabolic disorders increase the risk of GERD and IEM. Obesity has a greater impact on esophageal dysmotility and pathologic acid exposure than metabolic diseases.

Obesity is association with elevated risks of erosive esophagitis (EE), and metabolic abnormalities play crucial roles in its development. The aim of the study was to assess the association between metabolic obesity phenotypes and the risk of EE.

This retrospective study enrolled 11,599 subjects who had undergone upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University from January 1, 2008, to December 31, 2023. The enrolled individuals were grouped into four cohorts based on their metabolic health and obesity profiles, namely, metabolically healthy non-obesity (MHNO; n=2134, 18.4%), metabolically healthy obesity (MHO; n=1736, 15.0%), metabolically unhealthy non-obesity (MUNO; n=4290, 37.0%), and metabolically unhealthy obesity (MUO; n=3439, 29.6%). The relationships of the different phenotypes of metabolic obesity with the risks of developing EE in the different sexes and age groups were investigated by multivariate logistic regression analysis.

The MUNO, MHO, and MUO cohorts exhibited elevated risks of developing EE than the MHNO cohort. The confounding factors were adjusted for, and the findings revealed that the MUO cohort exhibited the greatest risk of EE, with odds ratios (ORs) of 5.473 (95% CI: 4.181-7.165) and 7.566 (95% CI: 5.718-10.010) for males and females, respectively. The frequency of occurrence of EE increased following an increase in proportion of metabolic risk factors. Subgroup analyses showed that the individuals under and over 60 years of age in the MHO, MUNO, and MUO cohorts exhibited elevated risks of developing EE. Further analysis suggested that obesity has a stronger influence on the risks of developing EE compared to metabolic disorders.

Metabolic disorders and obesity are both related with an elevated risk of EE, in which obesity has a potentially stronger influence. Clinical interventions should target both obesity and metabolic disorders to reduce EE risk.

The relationship between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) is complex. We aimed to determine the association of self-reported and objective sleep parameters with diverse manifestations of the GERD spectrum.

We prospectively recruited 561 individuals who underwent an electrocardiogram-based cardiopulmonary coupling for OSA screening during a health check-up. All participants received the Reflux Disease Questionnaire and an upper endoscopy to determine the presence of troublesome reflux symptoms and erosive esophagitis (EE). Sleep quality was evaluated by the Pittsburgh Sleep Quality Index and sleep dysfunction was defined as a Pittsburgh Sleep Quality Index score > 5. OSA was defined as a cardiopulmonary coupling-derived apnea-hypopnea index exceeding 15 events/h. Comparisons were made between participants on the GERD spectrum with respect to their various self-reported and objective sleep parameters.

Among the 277 patients with GERD (49.4%), 198 (35.3%) had EE. Patients with GERD had higher PSQI scores (6.99 ± 3.97 vs 6.07 ± 3.73, P = .005) and a higher prevalence of sleep dysfunction (60.6% vs 49.6%, P = .009). Patients with EE had a higher prevalence of OSA (42.9% vs 33.9%, P = .034). Along the GERD spectrum, symptomatic patients with EE had the highest PSQI scores and prevalence of sleep dysfunction (70.7%), while asymptomatic patients with EE had the highest prevalence of OSA (44%).

Our findings indicate a high prevalence of sleep dysfunction among individuals with GERD. Furthermore, patients on the GERD spectrum are prone to experiencing a range of self-reported and objective sleep disturbances.

Hu K-Y, Tseng P-H, Hsu W-C, et al. Association of self-reported and objective sleep disturbance with the spectrum of gastroesophageal reflux disease. J Clin Sleep Med. 2024;20(6):911-920.

Gastroesophageal reflux disease (GERD) is a prevalent global health concern with a rising incidence. Various risk factors, including obesity, hiatal hernia, and smoking, contribute to its development. Recent research suggests associations between GERD and metabolic syndrome, cardiac diseases, and hypertension (HTN). Mechanisms linking GERD to HTN involve autonomic dysfunction, inflammatory states, and endothelial dysfunction. Furthermore, GERD medications such as proton-pump inhibitors may impact blood pressure regulation. Conversely, antihypertensive medications like beta-blockers and calcium channel blockers can exacerbate GERD symptoms. While bidirectional causality exists between GERD and HTN, longitudinal studies are warranted to elucidate the precise relationship. Treatment of GERD, including anti-reflux surgery, may positively influence HTN control. However, the interplay of lifestyle factors, comorbidities, and medications necessitates further investigation to comprehensively understand this relationship. In this editorial, we comment on the article published by Wei et al in the recent issue of the World Journal of Clinical Cases. We evaluate their claims on the causal association between GERD and HTN.

The prevalence of reflux esophagitis (RE) is relatively high around the world. We investigated routine metabolic parameters for associations with RE prevalence and severity, creating a user-friendly RE prediction nomogram.

We included 10,881 individuals who had upper gastrointestinal endoscopy at a hospital. We employed univariate and multivariate logistic regression for independent risk factors related to RE prevalence, and conducted ordinal logistic regression for independent prognostic factors of RE severity. Subsequently, a nomogram was constructed using multivariate logistic regression analysis, and its performance was assessed through the utilization of receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) analysis.

In this study, 43.8% (4769 individuals) had confirmed RE. Multivariate analysis identified BMI, age, alcohol use, diabetes, Helicobacter pylori, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), albumin, uric acid (UA), fT3, and fT4 as independent RE risk factors (p < 0.05). The personalized nomogram used 17 factors to predict RE, with an AUC of 0.921 (95% CI: 0.916-0.926), specificity 84.02%, sensitivity 84.86%, and accuracy 84.39%, reflecting excellent discrimination. Calibration, decision, and CIC analyses affirmed the model's high predictive accuracy and clinical utility. Additionally, ordinal logistic regression linked hypertension, diabetes, HDL-C, LDL-C, TG, and TC to RE severity.

Our study highlights the association between the routine metabolic parameters and RE prevalence and severity. The nomogram may be of great value for the prediction of RE prevalence.

Reflux esophagitis has an increasing prevalence and complex and diverse symptoms. Identifying its risk factors is crucial to understanding the etiology, prevention, and management of the disease. The occurrence of reflux esophagitis may be associated with food reactions, Helicobacter pylori (H. pylori) infection, and metabolic syndromes.

To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin (Ig) G-mediated food intolerance, H. pylori infection, and metabolic syndrome on reflux esophagitis.

Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled. The patients' basic information, test results, gastroscopy results, H. pylori test results, and IgG-mediated food intolerance results were collected. Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis. Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H. pylori infection affecting reflux esophagitis.

A total of 7954 outpatients were included; the prevalence of reflux esophagitis, IgG-mediated food intolerance, H. pylori infection, and metabolic syndrome were 20.84%, 61.77%, 35.91%, and 60.15%, respectively. Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance (OR = 1.688, 95%CI: 1.497-1.903, P < 0.00001) and metabolic syndrome (OR = 1.165, 95%CI: 1.030-1.317, P = 0.01484), and the independent protective factor for reflux esophagitis was H. pylori infection (OR = 0.400, 95%CI: 0.351-0.456, P < 0.00001). IgG-mediated food intolerance had a partially positive mediating effect on H. pylori infection as it was associated with reduced occurrence of reflux esophagitis (P = 0.0200). Metabolic syndrome had a partially negative mediating effect on H. pylori infection and reduced the occurrence of reflux esophagitis (P = 0.0220).

Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis, while patients with H. pylori infection were at lower risk. IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H. pylori infection; however, metabolic syndrome increased the risk of patients with H. pylori infection developing reflux esophagitis.