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Tan Y, Zhang X, Lv XH, Sun YN, Yang JL, Xiao X. Glucagon-like peptide-1 receptor agonists increase the risk of residual gastric content and pulmonary aspiration on upper endoscopy: A meta-analysis. Dig Liver Dis 2025:S1590-8658(25)00281-6. [PMID: 40133086 DOI: 10.1016/j.dld.2025.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 02/02/2025] [Accepted: 03/01/2025] [Indexed: 03/27/2025]
Abstract
BACKGROUND AND AIMS Glucagon-like peptide-1 receptor agonists (GLP1-RA) are associated with increased residual gastric content (RGC); however, there is debate about their impact on RGC-related clinical outcomes, particularly aspiration. METHODS PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched for studies published up to January 4, 2025, comparing GLP1-RA with control groups (non-GLP1-RA) in patients undergoing endoscopy. The outcomes of interest included the risk of RGC, pulmonary aspiration, interrupted and repeated endoscopic procedures, and delays in gastric transit time during capsule endoscopy. For the meta-analysis, a random-effects model was used to calculate the pooled odds ratio (OR) and mean difference (MD) with 95 % confidence intervals (CIs). RESULTS Thirty-nine studies composed of a total of 1,253,498 subjects, were included. The pooled analysis demonstrated that the GLP1-RA group had a significantly increased risk of RGC (OR 4.86, 95 % CI 3.85-6.14; adjusted OR 5.24, 95 % CI 3.49-7.87), pulmonary aspiration (OR 2.29, 95 % CI 1.36-3.87), interrupted endoscopic procedures (OR 3.22, 95 % CI 1.65-6.29), repeated endoscopy (OR 2.16, 95 % CI 1.14-4.11), and delays in gastric transit time during capsule endoscopy (MD 45.51, 95 % CI 1.33-89.68). CONCLUSIONS GLP1-RA use increased the risk of RGC, pulmonary aspiration, interrupted and repeated endoscopy and gastric transit time, reducing the safety and completion of upper endoscopy.
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Affiliation(s)
- Ying Tan
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
| | - Xian Zhang
- Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
| | - Xiu-He Lv
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
| | - Yi-Ning Sun
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
| | - Jin-Lin Yang
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
| | - Xue Xiao
- Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
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Kornum DS, Krogh K, Keller J, Malagelada C, Drewes AM, Brock C. Diabetic gastroenteropathy: a pan-alimentary complication. Diabetologia 2025:10.1007/s00125-025-06365-y. [PMID: 39934370 DOI: 10.1007/s00125-025-06365-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
Autonomic neuropathy contributes to the pathophysiology of diabetic gastroenteropathy, which impacts the entire gastrointestinal tract alongside pancreatic and gallbladder functions. This is evident in the widespread morphological remodelling of the enteric nervous system, smooth muscle cells, interstitial cells of Cajal and vascular supply, causing pan-enteric motor, sensory and secretory disturbances. The gastrointestinal symptoms caused by these changes are often burdensome and non-specific and frequently coexist with poor glycaemic management and even malnutrition, impacting quality of life negatively. The Gastroparesis Cardinal Symptom Index and the Gastrointestinal Symptom Rating Scale are validated questionnaires for assessing gastrointestinal symptoms. However, clinical supplementary objective measures are essential. Transit time assessments are frequently used and typically evaluated using gastric emptying scintigraphy, breath tests or colonic radiopaque markers, but they cannot measure contractile activity or fluid transport. The primary treatment goals are to prevent further disease progression and to obtain symptomatic relief. Treatments include improved glycaemic management and dietary modifications, while pharmacological treatments target gastrointestinal symptoms, small intestinal bacterial overgrowth and exocrine pancreatic insufficiency. Invasive interventions may involve gastric peroral pyloromyotomy or the implantation of a gastric neurostimulator to manage pharmacologically refractory gastroparesis. This review describes the prevalence, pathophysiology, clinical presentation, assessment and treatment of diabetic gastrointestinal dysfunction within each segment of the gastrointestinal tract and directly connected exocrine organs.
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Affiliation(s)
- Ditte S Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jutta Keller
- Department of Internal Medicine, Israelitic Hospital, Academic Hospital University of Hamburg, Hamburg, Germany
| | - Carolina Malagelada
- Digestive System Research Unit, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.
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Cheng M, Ding F, Li L, Dai C, Sun X, Xu J, Chen F, Li M, Li X. Exploring the role of curcumin in mitigating oxidative stress to alleviate lipid metabolism disorders. Front Pharmacol 2025; 16:1517174. [PMID: 39950117 PMCID: PMC11822302 DOI: 10.3389/fphar.2025.1517174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/15/2025] [Indexed: 02/16/2025] Open
Abstract
Lipid metabolism plays a crucial role in maintaining homeostasis and overall health, as lipids are essential molecules involved in bioenergetic processes. An increasing body of research indicates that disorders of lipid metabolism can contribute to the development and progression of various diseases, including hyperlipidemia, obesity, non-alcoholic fatty liver disease (NAFLD), diabetes mellitus, atherosclerosis, and cancer, potentially leading to poor prognoses. The activation of the oxidative stress pathway disrupts lipid metabolism and induces cellular stress, significantly contributing to metabolic disorders. A well-documented crosstalk and interconnection between these metabolic disorders exists. Consequently, researchers have sought to identify antioxidant-rich substances in readily accessible everyday foods for potential use as complementary therapies. Curcumin, known for its anti-inflammatory and antioxidant properties, has been shown to enhance cellular antioxidant activity, mitigate oxidative stress, and alleviate lipid metabolism disorders by reducing reactive oxygen species (ROS) accumulation. These effects include decreasing fat deposition, increasing fatty acid uptake, and improving insulin sensitivity. A review of the existing literature reveals numerous studies emphasizing the role of curcumin in the prevention and management of metabolic diseases. Curcumin influences metabolic disorders through multiple mechanisms of action, with the oxidative stress pathway playing a central role in various lipid metabolism disorders. Thus, we aimed to elucidate the role of curcumin in various metabolic disorders through a unified mechanism of action, offering new insights into the prevention and treatment of metabolic diseases. Firstly, this article provides a brief overview of the basic pathophysiological processes of oxidative stress and lipid metabolism, as well as the role of oxidative stress in the pathogenesis of lipid metabolism disorders. Notably, the article reviews the role of curcumin in mitigating oxidative stress and in preventing and treating diseases associated with lipid metabolism disorders, including hyperlipidemia, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, obesity, and diabetes, thereby highlighting the therapeutic potential of curcumin in lipid metabolism-related diseases.
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Affiliation(s)
- Maojun Cheng
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Fang Ding
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Liyang Li
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Changmao Dai
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xiaolan Sun
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Jia Xu
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Feier Chen
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Mingxiu Li
- Sichuan No. 2 Hosptial of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Xueping Li
- Hosptial of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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Varma R, Williams CE, McClain ES, Bailey KR, Ordog T, Bharucha AE. Utility of a 13C-Spirulina Stable Isotope Gastric Emptying Breath Test in Diabetes Mellitus. Neurogastroenterol Motil 2025:e15008. [PMID: 39873950 DOI: 10.1111/nmo.15008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 11/07/2024] [Accepted: 01/06/2025] [Indexed: 01/30/2025]
Abstract
BACKGROUND The carbon-13 spirulina gastric emptying breath test (GEBT) is approved to identify delayed, but not accelerated, gastric emptying (GE). We compared the utility of the GEBT to scintigraphy for diagnosing abnormal GE in patients with diabetes mellitus. METHODS Twenty-eight patients with diabetes ate a 230-kcal test meal labeled with technetium 99 m and 13C-spirulina, after which 10 scintigraphic images and breath samples (baseline, 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min) were collected on 2 occasions 1 week apart. We assessed the accuracy of 13C-spirulina GEBT excretion rate (percent dose multiplied by 1000 [kPCD] min-1) values to predict scintigraphic half-life and distinguish between normal, delayed, and accelerated GE and the intraindividual reproducibility of the GEBT. KEY RESULTS Scintigraphy revealed normal, delayed, and accelerated GE, respectively, in 17 (30%), 29 (52%), and 10 (18%) test results. GE T½ values measured with scintigraphy and GEBT were highly concordant within individuals; the intraindividual reproducibility was 34% (scintigraphy) and 15% (GEBT). Compared to current criteria, the kPCD150 (150 min) and kPCD180 values provided equally sensitive (90%) and more specific (81% vs. 67%) approach for distinguishing between delayed versus normal/accelerated GE. A new metric (kPCD60-kPCD15 min) was 90% sensitive and 83% specific for distinguishing between accelerated versus normal/delayed GE. These findings were used to create nomograms and an algorithm for interpreting GEBT results. CONCLUSIONS AND INFERENCES Among patients with poorly controlled diabetes, the 13C-spirulina GEBT can accurately and precisely assess GE and effectively distinguish between normal, delayed, and accelerated GE.
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Affiliation(s)
- Revati Varma
- Division of Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | | | - Kent R Bailey
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota, USA
| | - Tamas Ordog
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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5
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Wattchow DA, Brookes SJH, Spencer NJ, De Giorgio R, Costa M, Dinning PG. Gut Neuropathies and Intestinal Motility Disorders. Neurogastroenterol Motil 2025:e14995. [PMID: 39777822 DOI: 10.1111/nmo.14995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 11/26/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND The enteric nervous system plays a key role in the coordination of gastrointestinal motility together with sympathetic, parasympathetic, and extrinsic sensory pathways. In some cases, abnormalities in neural activity in these pathways contribute to disorders of gut motility. Where this is associated with damage or death of enteric neurons, usually detected by microscopy, this is considered a gut neuropathy. PURPOSE This review summarizes recent advances in the identification of neuropathies in a range of gastrointestinal motility disorders.
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Affiliation(s)
- David A Wattchow
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
- Department of Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
| | - Simon J H Brookes
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Nick J Spencer
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Marcello Costa
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Phil G Dinning
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
- Department of Surgery, Flinders Medical Centre, Adelaide, South Australia, Australia
- Department of Gastroenterology, Flinders Medical Centre, Adelaide, South Australia, Australia
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6
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Shah VN, Peters AL, Umpierrez GE, Sherr JL, Akturk HK, Aleppo G, Bally L, Cengiz E, Cinar A, Dungan K, Fabris C, Jacobs PG, Lal RA, Mader JK, Masharani U, Prahalad P, Schmidt S, Zijlstra E, Ho CN, Ayers AT, Tian T, Aaron RE, Klonoff DC. Consensus Report on Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Treatment for Individuals With Type 1 Diabetes Using an Automated Insulin Delivery System. J Diabetes Sci Technol 2025; 19:191-216. [PMID: 39517127 PMCID: PMC11571606 DOI: 10.1177/19322968241291512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
With increasing prevalence of obesity and cardiovascular diseases, there is a growing interest in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as an adjunct therapy in type 1 diabetes (T1D). The GLP-1RAs are currently not approved by the US Food and Drug Administration for the treatment of T1D in the absence of randomized controlled trials documenting efficacy and safety of these agents in this population. The Diabetes Technology Society convened a series of three consensus meetings of clinicians and researchers with expertise in diabetes technology, GLP-1RA therapy, and T1D management. The project was aimed at synthesizing current literature and providing conclusions on the use of GLP-1RA therapy as an adjunct to automated insulin delivery (AID) systems in adults with T1D. The expert panel members met virtually three times on January 17, 2024, and April 24, 2024, and August 14, 2024, to discuss topics ranging from physiology and outcomes of GLP-1RAs in T1D to limitations of current sensors, algorithms, and insulin for AID systems. The panelists also identified research gaps and future directions for research. The panelists voted to in favor of 31 recommendations. This report presents the consensus opinions of the participants that, in adults with T1D using AID systems, GLP-1RAs have the potential to (1) provide effective adjunct therapy and (2) improve glycemic and metabolic outcomes without increasing the risk of severe hypoglycemia or diabetic ketoacidosis.
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Affiliation(s)
- Viral N. Shah
- Division of Endocrinology & Metabolism, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Anne L. Peters
- Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA
| | | | | | - Halis Kaan Akturk
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Grazia Aleppo
- Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Lia Bally
- Inselspital, University Hospital of Bern, University of Bern, Bern, Switzerland
| | - Eda Cengiz
- Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
| | - Ali Cinar
- Department of Chemical and Biological Engineering, Illinois Institute of Technology, Chicago, IL, USA
| | - Kathleen Dungan
- Division of Endocrinology, Diabetes and Metabolism, College of Medicine, The Ohio State University, Columbus, OH, USA
| | - Chiara Fabris
- Center for Diabetes Technology, School of Medicine, University of Virginia, Charlottesville, VA, USA
| | - Peter G. Jacobs
- Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA
| | - Rayhan A. Lal
- Division of Endocrinology, Department of Medicine, Stanford University, Stanford, CA, USA
- Division of Endocrinology, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA
| | - Julia K. Mader
- Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Umesh Masharani
- Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
| | - Priya Prahalad
- Division of Endocrinology, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA
| | | | | | - Cindy N. Ho
- Diabetes Technology Society, Burlingame, CA, USA
| | | | - Tiffany Tian
- Diabetes Technology Society, Burlingame, CA, USA
| | | | - David C. Klonoff
- Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA, USA
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7
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Changri L, Sun H, Bao Y, Zhang M. Rotigaptide inhibits spontaneous contractions of gastric smooth muscle in diabetic rats via the PKCα-Cx43 pathway. Cell Biol Int 2025; 49:92-100. [PMID: 39400417 DOI: 10.1002/cbin.12253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 09/19/2024] [Accepted: 09/24/2024] [Indexed: 10/15/2024]
Abstract
The study aimed to investigate the effect of rotigaptide (ZP123) on spontaneous contractions of gastric smooth muscle in diabetic rats and explore the underlying mechanisms. Twelve rats were randomly divided into model and normal control groups. Changes in gastric smooth muscle spontaneous contractions in each group were observed. Western blot analysis was performed to detect Cx43 and PKCα expression. Rat gastric smooth muscle cells were cultured in vitro and divided into normal glucose, high glucose and high glucose+rotigaptide group. The intracellular Ca2+ content was observed by immunofluorescence. The amplitude and frequency of gastric smooth muscle spontaneous contractions were reduced in the model group than the normal control group (all p < .01), which were reduced after rotigatide treatment than before treatment in the model group (all p < .01). The model+rotigaptide group showed decreased membrane expression of Cx43, increased cytoplasmic expression of Cx43, increased membrane expression of p-PKCα Thr497 and lower membrane/cytoplasm ratio of Cx43 expression compared with the model group (all p < .01). The intracellular Ca2+ content was increased in the high glucose group than the normal glucose group (p < .01), while no significant difference was observed between the high glucose+rotigaptide and high glucose groups. Our findings suggest that rotigatide can stabilize the intracellular Ca2+ concentration in gastric smooth muscle cells under high glucose condition by upregulating PKCα activity and downregulating the number of GJs and the opening rate of GJ hemichannels through the PKCα-Cx43 pathway, thus inhibiting spontaneous contractions of gastric smooth muscle in diabetic rats.
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Affiliation(s)
- Lu Changri
- Medical College, Yanbian University, Yanji, China
| | - Haibei Sun
- Medical College, Yanbian University, Yanji, China
| | - Yitegele Bao
- Medical College, Yanbian University, Yanji, China
| | - Mohan Zhang
- Medical College, Yanbian University, Yanji, China
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Changela S, Ashraf S, Lu JY, Duong KE, Henry S, Wang SH, Duong TQ. New-onset gastrointestinal disorders in COVID-19 patients 3.5 years post-infection in the inner-city population in the Bronx. Sci Rep 2024; 14:31850. [PMID: 39738536 PMCID: PMC11685902 DOI: 10.1038/s41598-024-83232-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/12/2024] [Indexed: 01/02/2025] Open
Abstract
This study examined the incidence, characteristics, and risk factors of new gastrointestinal disorders (GID) associated with SARS-CoV-2 infection up to 3.5 years post-infection. This retrospective study included 35,102 COVID-19 patients and 682,594 contemporary non-COVID-19 patients without past medical history of GID (controls) from the Montefiore Health System in the Bronx (3/1/2020 to 7/31/2023). Comparisons were made with unmatched and propensity-matched (1:2) controls. The primary outcome was new GID which included peptic ulcer, inflammatory bowel disease, irritable bowel syndrome, diverticulosis, diverticulitis, and biliary disease. Multivariate Cox proportional hazards model analysis was performed with adjustment for covariates. There were 2,228 (6.34%) COVID-19 positive patients who developed new GID compared to 38,928 (5.70%) controls. COVID-19 patients had an elevated risk of developing new GID (adjusted HR = 1.18 (95% CI 1.12-1.25) compared to propensity-matched controls, after adjusting for confounders that included smoking, obesity, diabetes, hypertension. These findings underscore the need for additional research and follow-up of at-risk individuals for developing GID post infection.
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Affiliation(s)
- Sagar Changela
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
| | - Samad Ashraf
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
| | - Justin Y Lu
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
| | - Kevin E Duong
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
| | - Sonya Henry
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
| | - Stephen H Wang
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Tim Q Duong
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
- Center for Health & Data Innovation, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
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9
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Aldali JA, Asseri MK, Almufarrij HA, Alromih AM, Alajlan AM, Alrashed KA, ALghadeer AI, Almutawa BI, Alshalani A. Prevalence of Gastroparesis and the Impact of Metformin in Diabetic Patients: A Cross-Sectional Study in Riyadh, Saudi Arabia. Gastroenterol Res Pract 2024; 2024:3713569. [PMID: 39664090 PMCID: PMC11634406 DOI: 10.1155/grp/3713569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 10/08/2024] [Accepted: 11/08/2024] [Indexed: 12/13/2024] Open
Abstract
Background: The prevalence of gastroparesis in individuals with diabetes mellitus varies significantly across different studies. This study is aimed at estimating the prevalence of gastroparesis among diabetic patients in Riyadh, Saudi Arabia, and evaluating the association between metformin use and clinical manifestations of gastroparesis. Methods: This cross-sectional study employed an online survey distributed via Google Forms, targeting patients at a diabetes clinic. The survey comprised three sections, including the Gastroparesis Cardinal Symptom Index (GCSI). Eligible participants were those diagnosed with either type 1 or type 2 diabetes mellitus and aged 18 or older. Results: The study included 385 participants, with the majority diagnosed with type 2 diabetes (55.6%) for over 10 years (59.5%). A significant proportion had poorly controlled blood glucose levels (56.6%) and were taking metformin (50.9%). Among gastrointestinal (GI) symptoms, "stomach fullness" was reported most frequently (53.2%), whereas "vomiting" was reported least often (17.9%). GCSI scores did not differ significantly between type 1 and type 2 diabetes patients (p = 0.88). However, patients with diabetes durations of less than 3 years, those with durations of 5-7 years controlled blood glucose levels, and those on metformin exhibited higher GCSI scores (p = 0.20, p = 0.02, and p = 0.10, respectively). Conclusion: This study identified some commonalities as well as differences in the prevalence and symptomatology of gastroparesis among diabetic patients. We observed no significant variation in GCSI scores between type 1 and type 2 diabetes. Nevertheless, higher GCSI scores were associated with shorter diabetes durations, controlled blood glucose levels, and metformin use. However, due to the small sample size and reliance on self-reported data, one should interpret the study's findings with caution.
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Affiliation(s)
- Jehad A. Aldali
- Department of Pathology, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
| | - Mushabbab K. Asseri
- Department of Endocrine & Diabetes, Prince Sultan Medical Military City, Riyadh 11159, Saudi Arabia
| | - Haneen A. Almufarrij
- Medical School, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), Riyadh 11481, Saudi Arabia
| | - Aroob M. Alromih
- Medical School, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
| | - Albandari M. Alajlan
- Medical School, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
| | - Khawlah A. Alrashed
- Medical School, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
| | - Atheer I. ALghadeer
- Medical School, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13317, Saudi Arabia
| | - Bushra I. Almutawa
- Medical School, College of Medicine, King Saud Bin Abdul Aziz University for Health Sciences (KSAU-HS), Riyadh 11481, Saudi Arabia
| | - Abdulrahman Alshalani
- Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
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10
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Kimura Y, Taniguchi M. Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice. Fitoterapia 2024; 179:106249. [PMID: 39395697 DOI: 10.1016/j.fitote.2024.106249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 09/09/2024] [Accepted: 10/09/2024] [Indexed: 10/14/2024]
Abstract
The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT3 receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT3 agonist. C. officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.
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Affiliation(s)
- Yoshiyuki Kimura
- Department of Biochemical Pharmacology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan; Department of Natural Product Research Sciences, Faculty of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, Nasahara, Takatsuki, Osaka, Japan.
| | - Masahiko Taniguchi
- Department of Natural Product Research Sciences, Faculty of Pharmaceutical Sciences, Osaka Medical and Pharmaceutical University, Nasahara, Takatsuki, Osaka, Japan
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11
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Sastre JA, López T, Julián R, Bustos D, Sanchís-Dux R, Molero-Díez YB, Sánchez-Tabernero Á, Ruiz-Simón FA, Sánchez-Hernández MV, Gómez-Ríos MÁ. Assessing Full Stomach Prevalence with Ultrasound Following Preoperative Fasting in Diabetic Patients with Dysautonomia: A Comparative Observational Study. Anesth Analg 2024; 139:1300-1308. [PMID: 39116006 DOI: 10.1213/ane.0000000000007110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
BACKGROUND Traditionally, diabetics have been considered patients with a high risk of aspiration due to having delayed gastric emptying; However, the evidence concerning residual gastric volume (GV) in fasting diabetic patients is inconsistent. This study aimed to compare the fasting GV of diabetic patients with or without dysautonomia with control patients scheduled for elective surgery using gastric ultrasound. METHODS This bicentric prospective single-blinded case-control study was conducted at 2 university hospitals in Spain. Patients aged over 18 years, classified as American Society of Anesthesiologists (ASA) physical statuses I to III and having similar fasting statuses, were included in the study. The primary outcome was to compare the prevalence of risk stomach using the Perlas gastric content grading scale evaluated by ultrasound in the 3 groups. Secondary outcomes included the measurement of cross-sectional area (CSA) and GV in the right lateral decubitus (RLD) position, as well as the prevalence of solid gastric residue. RESULTS A total of 289 patients were recruited for the study, comprising 145 diabetic patients (83 of whom had dysautonomia) and 144 patients in the control group. The percentage of patients classified as Perlas grade 2 was 13.2% in the control group, 16.1% in diabetic patients without dysautonomia, and 22.9% in diabetic patients with dysautonomia ( P = .31). Antral CSA was significantly higher in diabetic patients with dysautonomia (6.5 [4.8-8.4]) compared to the control group (5.4 [4.0-7.2]; P = .04). However, no significant differences were observed between groups in residual GV. Among diabetic patients with dysautonomia, 12% exhibited solid gastric residue, which was twice the percentage observed in diabetic patients without dysautonomia (4.8%) and 3 times higher than that in the control group (3.5%; P = .03). The presence of dysautonomia was associated with an increased odds ratio of solid gastric residue (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.28-8.87; P = .01) after adjusting for confounding factors. CONCLUSIONS This study offers insights into the relationship between dysautonomia in patients with diabetes mellitus and the presence of full stomach, underscoring the significance of preoperative gastric ultrasound evaluation in managing perioperative risks in this population.
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Affiliation(s)
- José A Sastre
- From the Department of Anesthesiology, Salamanca University Hospital, Salamanca, Spain
| | - Teresa López
- From the Department of Anesthesiology, Salamanca University Hospital, Salamanca, Spain
| | - Roberto Julián
- Department of Anesthesiology, Hospital Virgen de la Concha, Zamora, Spain
| | - Domingo Bustos
- From the Department of Anesthesiology, Salamanca University Hospital, Salamanca, Spain
| | - Raquel Sanchís-Dux
- Department of Anesthesiology, Hospital Virgen de la Concha, Zamora, Spain
| | | | | | | | | | - Manuel Á Gómez-Ríos
- Department of Anesthesiology and Perioperative Medicine, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain
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12
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McCallum RW, Parkman HP, Fass R, Bhandari BR, Carlson MR, Buck RD. Metoclopramide Nasal Spray in Women With Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study. Clin Gastroenterol Hepatol 2024; 22:2497-2505.e5. [PMID: 37924856 DOI: 10.1016/j.cgh.2023.10.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 10/19/2023] [Accepted: 10/24/2023] [Indexed: 11/06/2023]
Abstract
BACKGROUND & AIMS Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared with placebo in reducing symptoms of diabetic gastroparesis in women. METHODS This US multicenter, randomized, double-blind, parallel group study enrolled women aged 18-75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy end point was change in mean daily Gastroparesis Symptom Assessment total score from baseline to Week 4. The Gastroparesis Symptom Assessment daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a 5-point ordinal scale. RESULTS Two hundred and five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared with the placebo group from baseline to Week 4 (P = .881). However, subjects with moderate-to-severe symptoms at baseline had a significant treatment effect from Weeks 1 to 3 (P < .05) and experienced a significant reduction in nausea and upper abdominal pain for all 4 weeks versus placebo (P < .05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently. CONCLUSIONS Although the primary end point was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate-to-severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. (ClinicalTrials.gov identifier: NCT02025725.).
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Affiliation(s)
- Richard W McCallum
- Internal Medicine, Division of Gastroenterology, Texas Tech University Health Sciences Center, El Paso, Texas.
| | - Henry P Parkman
- GI Motility Laboratory, Gastroenterology, Department of Medicine, Temple University Hospital, Philadelphia, Pennsylvania
| | - Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, Ohio
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13
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Wang X, Ma L, Jiang M, Zhu H, Ni C, Yang X, Hu J, Zhang HH. Analysis of gastric electrical rhythm in patients with type 2 diabetes mellitus. Endocrine 2024; 86:612-619. [PMID: 38861116 PMCID: PMC11489290 DOI: 10.1007/s12020-024-03908-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 05/30/2024] [Indexed: 06/12/2024]
Abstract
AIM To analysis the change of electrogastrogram (EGG) in patients with type 2 diabetes mellitus (T2DM), and evaluate the prevalence of abnormal gastric electrical rhythm (AGER) and its relative influencing factors. METHODS A total of 65 patients with T2DM hospitalized at the Second Affiliated Hospital of Soochow University from Dec. 2020 to Dec. 2021 were included in the cross-sectional study. General information, clinical data, and medical history data of all study subjects, including name, gender, body mass index (BMI), duration of diabetes, anti-diabetic therapies, high blood pressure (HBP) history, smoking history, and medication history, were completely collected. The results of laboratory tests, including biochemical parameters, glycosylated hemoglobin (HbA1c), fasting C-peptide, 2 h postprandial C-peptide, 24 h urine total protein (24 hUTP), urine microalbumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were recorded. EGG, Gastroparesis Cardinal Symptom Index (GCSI), gastric emptying ultrasound, fundus examination, carotid artery ultrasonography, cardiac autonomic function test, heart rate variability (HRV) were all examined and recorded as well. According to the results of EGG, the subjects were divided into normal gastric electrical rhythm (NGER) group and abnormal gastric electrical rhythm (AGER) group. RESULTS (1) Fasting blood glucose (FBG), HbA1c, the presence of diabetic peripheral neuropathy (DPN) and diabetic cardiac autonomic neuropathy (DCAN) were significantly higher in the AGER group (p < 0.05). Low frequency (LF) and high frequency (HF), the indicators of HRV, were significantly lower in the AGER group (p < 0.05). In addition, the prevalence of feeling excessively full after meals, loss of appetite, and stomach or belly visibly larger after meals of gastrointestinal symptoms of gastroparesis were significantly higher in the AGER group (p < 0.05). Multiple logistic regression analysis showed that FBG and the prevalence of DCAN were the independent risk factors. CONCLUSION AGER was associated with high FBG and the presence of DCAN. EGG examination is recommended for patients with gastrointestinal symptoms and clues of DCAN.
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Affiliation(s)
- Xixi Wang
- The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Lianhua Ma
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Miao Jiang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- NO.2 People's Hospital of Fuyang City, Fuyang, China
| | - Hong Zhu
- The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China
| | - Chendong Ni
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | | | - Ji Hu
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
| | - Hong-Hong Zhang
- Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.
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14
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Kornum DS, Brock C, Okdahl T, Bertoli D, Kufaishi H, Wegeberg AM, Høyer KL, Mark EB, Brock B, Hansen CS, Knop FK, Drewes AM, Krogh K. Diabetic gastroenteropathy: Associations between gastrointestinal symptoms, motility, and extraintestinal autonomic measures. Neurogastroenterol Motil 2024:e14956. [PMID: 39485948 DOI: 10.1111/nmo.14956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 10/03/2024] [Accepted: 10/21/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers. METHODS We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function. KEY RESULTS Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04-1.35), p = 0.01; GSRS: 1.15 (1.03-1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03-1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89-0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03-1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16-1.19), p = 0.03; GSRS: 0.87 (0.30-1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers. CONCLUSIONS & INFERENCES Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived.
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Affiliation(s)
- Ditte S Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Tina Okdahl
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Thisted Research Unit, Aalborg University Hospital Thisted, Aalborg, Denmark
| | - Katrine L Høyer
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Esben B Mark
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | | | - Filip K Knop
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk A/S, Bagsværd, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
- Thisted Research Unit, Aalborg University Hospital Thisted, Aalborg, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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15
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Fan MW, Tian JL, Chen T, Zhang C, Liu XR, Zhao ZJ, Zhang SH, Chen Y. Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications. World J Diabetes 2024; 15:2041-2057. [PMID: 39493568 PMCID: PMC11525733 DOI: 10.4239/wjd.v15.i10.2041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 08/14/2024] [Accepted: 08/26/2024] [Indexed: 09/26/2024] Open
Abstract
Diabetes mellitus (DM) is one of the major causes of mortality worldwide, with inflammation being an important factor in its onset and development. This review summarizes the specific mechanisms of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway in mediating inflammatory responses. Furthermore, it comprehensively presents related research progress and the subsequent involvement of this pathway in the pathogenesis of early-stage DM, diabetic gastroenteropathy, diabetic cardiomyopathy, non-alcoholic fatty liver disease, and other complications. Additionally, the role of cGAS-STING in autonomic dysfunction and intestinal dysregulation, which can lead to digestive complications, has been discussed. Altogether, this study provides a comprehensive analysis of the research advances regarding the cGAS-STING pathway-targeted therapeutic agents and the prospects for their application in the precision treatment of DM.
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Affiliation(s)
- Ming-Wei Fan
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Jin-Lan Tian
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Tan Chen
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Can Zhang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Xin-Ru Liu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Zi-Jian Zhao
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Shu-Hui Zhang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Yan Chen
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
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16
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Xu H, Miao F, Fan Y. A bibliometric analysis of diabetic gastroparesis from 1979 to 2024. Front Med (Lausanne) 2024; 11:1445276. [PMID: 39450111 PMCID: PMC11500038 DOI: 10.3389/fmed.2024.1445276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 09/09/2024] [Indexed: 10/26/2024] Open
Abstract
Objective Gastroparesis is one of the complications of diabetes mellitus, which has a major impact on the quality of life of patients, and the limited therapeutic options currently available make it a public health problem. No bibliometric studies on diabetic gastroparesis have been published to date. Therefore, the aim of this paper is to summarize and analyze the research hotspots for researchers. Methods Research articles related to Diabetic gastroparesis were searched in Web of Science Core Collection (WOSCC), and relevant information was extracted after screening. A comprehensive bibliometric analysis of 699 publications was conducted using Microsoft Excel 2019, Citespace and VOSviewers. Result A total of 699 papers from 738 institutions in 41 countries were retrieved. Publications in this field have increased rapidly since 1979. USA (n = 370) and Mayo Clinical (n = 69) were the most productive country and institution, respectively. Neurogastroenterology and Motility (n = 67) was the most published journal with Parkman, Henry P. (n = 40) having the highest number of articles; Gastroenterology and Mccallum, Richard W. were the most influential journals and authors. Conclusions The research hotspots of Diabetic gastroparesis are mainly focused on treatment modalities and pathological mechanisms. Future research in diabetic gastroparesis will focus on exploring the pathomechanisms, finding long-term effective treatments, and improving patients' quality of life.
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Affiliation(s)
| | | | - Yushan Fan
- College of Acupuncture-Moxibustion and Tuina, Guangxi University of Chinese Medicine, Nanning, China
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17
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Yaghmour KA, Al Shamrani NA, Alshamrani FM, Alluhib SA, Alghamdi EA, Alghamdi WS. Prevalence and Severity of Diabetic Gastroparesis Symptoms in Relation to Diabetics in Saudi Arabia. Cureus 2024; 16:e71920. [PMID: 39564066 PMCID: PMC11574914 DOI: 10.7759/cureus.71920] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND Gastroparesis is a chronic illness characterized by delayed emptying of the stomach without any mechanical obstruction and therefore presents with conditions such as bloating, early satiety, and abdominal pain, among others. In the Kingdom of Saudi Arabia population, it is a major risk factor because, through review, one can find very limited data on the prevalence and severity of the atrophic gastritis condition among diabetes populations in the region. OBJECTIVES The objectives of this study were to determine the magnitude and severity of symptoms of gastroparesis in type 1 and type 2 diabetic patients in Saudi Arabia, for information-based decision-making in health practices and policy. METHODS The design of the study, in the present research, is descriptive, cross-sectional, and non-intervening. Information is directly collected for this study from the 119 diabetic patients, both type 1 and type 2, directly by having interviews and telephone surveys during 2023-2024. Patients belong to the age group of 18-69 years; patient participation in the study is voluntary. The Gastroparesis Cardinal Symptom Index is used for scoring the prevalence followed by the symptoms. Descriptive and inferential statistics with the chi-square test and logistic regression models were used to analyze data. RESULTS In this study, 68.4% were type 2 and 63.4% were type 1 diabetic patients and more than half of those with type 2 diabetes were in the age range of 50 to 59 years, while the ages of type 1 diabetic patients were evenly distributed. Key findings from this study are: There was a rate of 22.0% for the occurrence of moderate nausea in type 1 and 29.1% in type 2. Vomiting was infrequent in Type 2 (49.4%) compared to Type 1 (31%). Symptom severity: A significant statistical difference was judged by the feeling of stomach fullness (p = 0.038), with more occurrences among the type 2 DM patients. On univariate analysis, symptoms were more severe in younger patients (< 60 years). There were clear socio-economic disparities; non-Saudi nationals and those of a lower educational and income status reported much more severe symptomatology. CONCLUSION This sign- and symptom-based substantiated research was done in Saudi Arabia to identify whether gastroparesis prevalence and severity differ in type 1 and type 2 diabetic patients. More patients suffering were young and had type 2 diabetes and low socio-economic status. Such findings would surely accentuate the need and call for indispensable, targeted interventions from more longitudinal studies, for a better approach and understanding of diabetic gastroparesis.
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Affiliation(s)
- Khaled A Yaghmour
- Department of Family Medicine, King Abdulaziz University, Jeddah, SAU
| | | | | | | | | | - Waleed S Alghamdi
- Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, SAU
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18
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Kim TY, De R, Choi I, Kim H, Hahn SK. Multifunctional nanomaterials for smart wearable diabetic healthcare devices. Biomaterials 2024; 310:122630. [PMID: 38815456 DOI: 10.1016/j.biomaterials.2024.122630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 05/19/2024] [Indexed: 06/01/2024]
Abstract
Wearable diabetic healthcare devices have attracted great attention for real-time continuous glucose monitoring (CGM) using biofluids such as tears, sweat, saliva, and interstitial fluid via noninvasive ways. In response to the escalating global demand for CGM, these devices enable proactive management and intervention of diabetic patients with incorporated drug delivery systems (DDSs). In this context, multifunctional nanomaterials can trigger the development of innovative sensing and management platforms to facilitate real-time selective glucose monitoring with remarkable sensitivity, on-demand drug delivery, and wireless power and data transmission. The seamless integration into wearable devices ensures patient's compliance. This comprehensive review evaluates the multifaceted roles of these materials in wearable diabetic healthcare devices, comparing their glucose sensing capabilities with conventionally available glucometers and CGM devices, and finally outlines the merits, limitations, and prospects of these devices. This review would serve as a valuable resource, elucidating the intricate functions of nanomaterials for the successful development of advanced wearable devices in diabetes management.
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Affiliation(s)
- Tae Yeon Kim
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Ranjit De
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Inhoo Choi
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea
| | - Hyemin Kim
- Department of Cosmetics Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, South Korea.
| | - Sei Kwang Hahn
- Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk, 37673, South Korea.
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19
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Li S, Wang G. External application of traditional Chinese medicine to treat diabetic gastroparesis. Asian J Surg 2024; 47:4427-4428. [PMID: 39068074 DOI: 10.1016/j.asjsur.2024.07.184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 07/21/2024] [Indexed: 07/30/2024] Open
Affiliation(s)
- Siyun Li
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, People's Republic of China
| | - Gang Wang
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, People's Republic of China.
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20
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Tustumi F, Ho V, Payne SC, Carra RB. Editorial: Gastrointestinal autonomic disorders. Front Neurol 2024; 15:1492409. [PMID: 39403269 PMCID: PMC11471610 DOI: 10.3389/fneur.2024.1492409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 09/17/2024] [Indexed: 01/04/2025] Open
Affiliation(s)
- Francisco Tustumi
- Department of Gastroenterology, Instituto do cancer do Estado de São Paulo, São Paulo, SP, Brazil
- Department of Health Sciences, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Vincent Ho
- Department of Gastroenterology, Western Sydney University, Penrith, NSW, Australia
| | - Sophie Clementine Payne
- Department of Medical Bionics, University of Melbourne, Melbourne, VIC, Australia
- Bionics Institute, Melbourne, VIC, Australia
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21
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Varma R, Chakraborty SC, Ramu SK, Burton DD, Deb B, Ryks MD, Feuerhak KJ, Bailey KR, Bharucha AE. Effects of ondansetron on symptoms during a gastric emptying study and enteral lipid challenge and on daily symptoms in diabetic gastroenteropathy. Neurogastroenterol Motil 2024; 36:e14857. [PMID: 38946172 PMCID: PMC11321918 DOI: 10.1111/nmo.14857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 05/24/2024] [Accepted: 06/17/2024] [Indexed: 07/02/2024]
Abstract
BACKGROUND This study compared the effects of ondansetron and placebo in patients with diabetes mellitus and symptoms of dyspepsia (diabetic gastroenteropathy [DGE]). METHODS We performed a randomized, double-blinded, placebo-controlled study of ondansetron tablets (8 mg) three times daily for 4 weeks in DGE patients. Symptoms were assessed with the Gastroparesis Cardinal Symptom Index daily diaries. Gastric emptying (GE) of solids (scintigraphy) and duodenal lipid infusions (300 kcal over 2 h) were each assessed twice, with placebo and ondansetron. Drug effects on GE, symptoms during the GE study and during lipid infusion, and daily symptoms were analyzed. KEY RESULTS Of 41 patients, 37 completed both GE studies and one completed 1; 31 completed both lipid infusions and four only placebo; and all 35 randomized patients completed 4 weeks of treatment. Compared to placebo, ondansetron reduced the severity of fullness (p = 0.02) and belching (p = 0.049) during lipid infusion but did not affect GE T1/2. Both ondansetron and placebo improved daily symptoms versus the baseline period (p < 0.05), but the differences were not significant. In the analysis of covariance of daily symptoms during the treatment period, the interaction term between treatment and the acute effect of ondansetron on symptoms during lipid challenge was significant (p = .024). CONCLUSIONS & INFERENCES Ondansetron significantly reduced fullness during enteral lipid infusion in patients with DGE. Overall, ondansetron did not improve daily symptoms versus placebo. But patients in whom ondansetron improved symptoms during enteral lipid challenge were perhaps more likely to experience symptom relief during daily treatment.
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Affiliation(s)
- Revati Varma
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Duane D. Burton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Brototo Deb
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Michael D. Ryks
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Kelly J. Feuerhak
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Kent R. Bailey
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Adil E. Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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22
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Huang J, Song Y, Cheng S, Yang X. Mechanism of action of FoxiangSan in diabetic gastroparesis: Gut microbiota and cAMP/PKA pathway. Heliyon 2024; 10:e35558. [PMID: 39211931 PMCID: PMC11357790 DOI: 10.1016/j.heliyon.2024.e35558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 07/24/2024] [Accepted: 07/31/2024] [Indexed: 09/04/2024] Open
Abstract
Diabetic gastroparesis, a common complication of type 2 diabetes (T2DM), presents a significant treatment challenge. FoxiangSan is emerging as a potential therapy. FoxiangSan is a traditional Chinese medicine formula with the potential for treating diabetic gastroparesis by modulating gut microbiota and cAMP/PKA signaling pathways. This study explores the mechanisms behind FoxiangSan's effects on T2DM-induced gastroparesis, focusing on its impact on gut microbiota and the cAMP/PKA pathway. A rat model of type 2 diabetic gastroparesis was established through a high-fat diet and streptozotocin (STZ) injection, and the effects of FoxiangSan were assessed. Additionally, protein expression related to the cAMP/PKA pathway was examined, and FoxiangSan's influence on gut microbiota was studied using 16S rRNA sequencing. FoxiangSan significantly alleviated hyperglycemia, improved gastric pathology in rats with gastroparesis, enhanced the expression of 5-HT4, cAMP, PKA, and pPKA in the gastric antrum, and rebalanced gut microbiota. FoxiangSan demonstrates the therapeutic potential for T2DM-associated gastroparesis by modulating the cAMP/PKA pathway and gut microbiota.
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Affiliation(s)
- Jukai Huang
- Department of Endocrinology, Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing, 100700, PR China
| | - Yaling Song
- Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, PR China
| | - Shuli Cheng
- Department of Intensive Care Unit, Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing, 100700, PR China
| | - Xiaohui Yang
- Department of Endocrinology, Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing, 100700, PR China
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23
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Vasatko M, Evinova E, Hugova K, Simkova D, Yepishkina K, Amin S, Martinek J. Endoscopic pyloromyotomy for treatment of gastroparesis: A new standard or still an experimental approach? Best Pract Res Clin Gastroenterol 2024; 71:101910. [PMID: 39209413 DOI: 10.1016/j.bpg.2024.101910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 04/03/2024] [Indexed: 09/04/2024]
Abstract
Gastroparesis (GP) can be a severe and debilitating disease. Its pathophysiology is complex and not completely understood. Two principal mechanisms are responsible for the development of symptoms - gastric hypomotility and pylorospasm. Pylorus targeted therapies aim to decrease presumably elevated pyloric tone - pylorospasm. There is a growing body of evidence about their role in the treatment algorithm of GP. G-POEM (endoscopic pyloromyotomy) is an extensively studied pylorus targeted therapy. Its efficacy ranges between 56 and 80% and the number of recurrences among those with treatment effect seems low. G-POEM is a safe procedure with very low frequency of severe adverse events. At present, G-POEM should not be considered as an experimental approach and may be offered to all patients with refractory and severe GP. Nevertheless, G-POEM is not a first line treatment. Conservative measures such as diet modification and pharmacotherapy should always be tried before G-POEM is considered. Further research must focus on better patient selection as at present there are no standardized criteria. Functional imaging such as impedance planimetry (EndoFlip) may hold promise in this regard.
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Affiliation(s)
- Martin Vasatko
- Department of Hepatogastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Physiology, Charles University in Prague, Prague, Czech Republic
| | - Eva Evinova
- Institute of Physiology, Charles University in Prague, Prague, Czech Republic; Department of Gastroenterology, Vitkovice Hospital, Czech Republic
| | - Kristina Hugova
- Department of Hepatogastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Physiology, Charles University in Prague, Prague, Czech Republic
| | - Dagmar Simkova
- Department of Hepatogastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Physiology, Charles University in Prague, Prague, Czech Republic
| | - Katerina Yepishkina
- Department of Hepatogastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic
| | - Sunil Amin
- Division of Digestive Health and Liver Disease, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Jan Martinek
- Department of Hepatogastroenterology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic; Institute of Physiology, Charles University in Prague, Prague, Czech Republic; Faculty of Medicine, Ostrava University, Ostrava, Czech Republic.
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24
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Vaganova AN, Markina AA, Belousov AM, Lenskaia KV, Gainetdinov RR. Dopamine Receptors and TAAR1 Functional Interaction Patterns in the Duodenum Are Impaired in Gastrointestinal Disorders. Biomedicines 2024; 12:1590. [PMID: 39062162 PMCID: PMC11274761 DOI: 10.3390/biomedicines12071590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/20/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Currently, there is a growing amount of evidence for the involvement of dopamine receptors and the functionally related trace amine-associated receptor, TAAR1, in upper intestinal function. In the present study, we analyzed their expression in the duodenum using publicly accessible transcriptomic data. We revealed the expression of DRD1, DRD2, DRD4, DRD5, and TAAR1 genes in different available datasets. The results of the gene ontology (GO) enrichment analysis for DRD2 and especially TAAR1 co-expressed genes were consistent with the previously described localization of D2 and TAAR1 in enteric neurons and secretory cells, respectively. Considering that co-expressed genes are more likely to be involved in the same biological processes, we analyzed genes that are co-expressed with TAAR1, DRD2, DRD4, and DRD5 genes in healthy mucosa and duodenal samples from patients with functional dyspepsia (FD) or diabetes-associated gastrointestinal symptoms. Both pathological conditions showed a deregulation of co-expression patterns, with a high discrepancy between DRDs and TAAR1 co-expressed gene sets in normal tissues and patients' samples and a loss of these genes' functional similarity. Meanwhile, we discovered specific changes in co-expression patterns that may suggest the involvement of TAAR1 and D5 receptors in pathologic or compensatory processes in FD or diabetes accordingly. Despite our findings suggesting the possible role of TAAR1 and dopamine receptors in functional diseases of the upper intestine, underlying mechanisms need experimental exploration and validation.
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Affiliation(s)
- Anastasia N. Vaganova
- Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia; (A.N.V.)
- St. Petersburg State University Hospital, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia;
| | - Alisa A. Markina
- Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia; (A.N.V.)
| | - Aleksandr M. Belousov
- St. Petersburg State University Hospital, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia;
| | - Karina V. Lenskaia
- Department of Medicine, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia;
| | - Raul R. Gainetdinov
- Institute of Translational Biomedicine, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia; (A.N.V.)
- St. Petersburg State University Hospital, St. Petersburg State University, Universitetskaya nab. 7/9, 199034 St. Petersburg, Russia;
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25
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Liu R, He M, Zhao X, Sun M, Cao J, Wang X, Wang X, Zhao S, Wang F, Li T. Effects of stimulating single acupoint and combination acupoints on diabetic gastroparesis: A randomised controlled trial study. J Tradit Complement Med 2024; 14:446-455. [PMID: 39035685 PMCID: PMC11259726 DOI: 10.1016/j.jtcme.2024.01.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 01/09/2024] [Accepted: 01/21/2024] [Indexed: 07/23/2024] Open
Abstract
Background and aim The most effective among the acupoints remains to be determined for treating diabetic gastroparesis (DGP). This study aimed to compare single and combination acupoints for their effectiveness in DGP. Experimental procedure A prospective, patient-assessor-blinded randomised controlled trial was designed to compare the efficacy of 8-week acupuncture at a single acupoint (Zhongwan, CV-12), combination acupoints (Zhongwan, CV-12 and Zusanli, ST-36), and a sham-acupoint, in 99 adults with DGP. The primary clinical outcome was measured using the Gastroparesis Cardinal Symptom Index (GCSI), while barium meal examination, fasting plasma glucose, the 2-h plasma glucose, short-form health survey (SF-36), and GCSI subscales were performed for evaluating secondary clinical outcomes. These results were analysed by two factorial analysis of variance (ANOVA) test, Chi-Square, Fisher Exact, Kruskal-Wallis tests and Tukey's Honest Significant Difference (HSD) test. Results After randomization, 97 patients completed the study. GCSI scores of all groups decreased during both post-treatment and the follow-up period, they were statistically significant compared to the baseline period (p < 0.01), but there was no significant difference among the groups (p > 0.05) during the post-treatment period. GCSI scores improved more in the combination acupoints group than in the single acupoint group which was better than the sham group after treatment. During the follow-up period, the same trend was observed. Conclusions Among patients with DGP, the combination acupoints were more beneficial compared with single and sham acupoints. Trial registration number NCT02452489.
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Affiliation(s)
- Renming Liu
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Min He
- Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, PR China
| | - Xuewei Zhao
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Mengmeng Sun
- Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, PR China
| | - Jiazhen Cao
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Xinyue Wang
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Xingbang Wang
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Shuming Zhao
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Fuchun Wang
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
- The “973” National Basic Research Program of China, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
| | - Tie Li
- Department of Acupuncture and Moxibustion, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, PR China
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26
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Varma R, Chakraborty S, Burton DD, Bailey KR, Bharucha AE. Small intestinal bacterial overgrowth in diabetic gastroenteropathy. Neurogastroenterol Motil 2024; 36:e14798. [PMID: 38651669 DOI: 10.1111/nmo.14798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/06/2024] [Accepted: 04/03/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE. METHODS In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO. KEY RESULTS Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006). CONCLUSIONS & INFERENCES Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.
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Affiliation(s)
- Revati Varma
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Duane D Burton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kent R Bailey
- Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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27
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Abdalla MMI. Enteric neuropathy in diabetes: Implications for gastrointestinal function. World J Gastroenterol 2024; 30:2852-2865. [PMID: 38947292 PMCID: PMC11212710 DOI: 10.3748/wjg.v30.i22.2852] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 05/04/2024] [Accepted: 05/21/2024] [Indexed: 06/05/2024] Open
Abstract
Diabetes, commonly known for its metabolic effects, also critically affects the enteric nervous system (ENS), which is essential in regulating gastrointestinal (GI) motility, secretion, and absorption. The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions, such as gastroparesis and irregular bowel habits, primarily due to disruptions in the function of neuronal and glial cells within the ENS, as well as oxidative stress and inflammation. This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients. Additionally, it discusses the latest advances in diagnostic approaches, emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals. The editorial also reviews current and emerging therapeutic strategies, focusing on pharmacological treatments, dietary management, and potential neuromodulatory interventions. Ultimately, this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes, aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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28
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Kornum DS, Bertoli D, Kufaishi H, Wegeberg AM, Okdahl T, Mark EB, Høyer KL, Frøkjær JB, Brock B, Krogh K, Hansen CS, Knop FK, Brock C, Drewes AM. Transcutaneous vagal nerve stimulation for treating gastrointestinal symptoms in individuals with diabetes: a randomised, double-blind, sham-controlled, multicentre trial. Diabetologia 2024; 67:1122-1137. [PMID: 38546822 PMCID: PMC11058613 DOI: 10.1007/s00125-024-06129-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 02/06/2024] [Indexed: 04/30/2024]
Abstract
AIMS/HYPOTHESIS Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).
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Affiliation(s)
- Ditte S Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Thisted Research Unit, Aalborg University Hospital Thisted, Thisted, Denmark
| | - Tina Okdahl
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Esben B Mark
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Katrine L Høyer
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jens B Frøkjær
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Department of Radiology, Aalborg University Hospital, Aalborg, Denmark
| | | | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | - Filip K Knop
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
- Thisted Research Unit, Aalborg University Hospital Thisted, Thisted, Denmark.
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.
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29
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Wang Z, Liu T, Cao D, Luo H, Yang Z, Kang X, Pan Y. The associations between functional dyspepsia and potential risk factors: A comprehensive Mendelian randomization study. PLoS One 2024; 19:e0302809. [PMID: 38718064 PMCID: PMC11078438 DOI: 10.1371/journal.pone.0302809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 04/13/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Previous cross-sectional studies have identified multiple potential risk factors for functional dyspepsia (FD). However, the causal associations between these factors and FD remain elusive. Here we aimed to fully examine the causal relationships between these factors and FD utilizing a two-sample MR framework. METHODS A total of 53 potential FD-related modifiable factors, including those associated with hormones, metabolism, disease, medication, sociology, psychology, lifestyle and others were obtained through a comprehensive literature review. Independent genetic variants closely linked to these factors were screened as instrumental variables from genome-wide association studies (GWASs). A total of 8875 FD cases and 320387 controls were available for the analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach to assess the relationship between genetic variants of risk factors and the FD risk. Sensitivity analyses were performed to evaluate the consistency of the findings using the weighted median model, MR-Egger and MR-PRESSO methods. RESULTS Genetically predicted depression (OR 1.515, 95% confidence interval (CI) 1.231 to 1.865, p = 0.000088), gastroesophageal reflux disease (OR 1.320, 95%CI 1.153 to 1.511, p = 0.000057) and years of education (OR 0.926, 95%CI 0.894 to 0.958, p = 0.00001) were associated with risk for FD in univariate MR analyses. Multiple medications, alcohol consumption, poultry intake, bipolar disorder, mood swings, type 1 diabetes, elevated systolic blood pressure and lower overall health rating showed to be suggestive risk factors for FD (all p<0.05 while ≥0.00167). The positive causal relationship between depression, years of education and FD was still significant in multivariate MR analyses. CONCLUSIONS Our comprehensive MR study demonstrated that depression and lower educational attainment were causal factors for FD at the genetic level.
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Affiliation(s)
- Zeyu Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
| | - Tangyi Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
| | - Dan Cao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
| | - Hui Luo
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
| | - Ze Yang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
| | - Xiaoyu Kang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
| | - Yanglin Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi an, China
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Kędzierska-Kapuza K, Safranow K, Niewiński K, Niewiński G, Durlik M, Szczuko M. Indices of Nutrition Status of Kidney and Pancreas Transplant Candidates. Transplant Proc 2024; 56:813-821. [PMID: 38692964 DOI: 10.1016/j.transproceed.2024.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/28/2024] [Accepted: 03/29/2024] [Indexed: 05/03/2024]
Abstract
Nutritional assessment is used to implement early nutritional interventions and reduce complications associated with malnutrition, which plays a crucial role in improving postoperative outcomes for patients undergoing pancreas and/or kidney transplantation. OBJECTIVE The aim of this study was to analyze the nutritional status (NS) in patients eligible for kidney transplantation (KTx) and simultaneous kidney-pancreas transplantation (SPKTx). METHODS We analyzed the database of hospitalized patients from 2020 to 2023 to identify preoperative parameters of NS in patients eligible for KTx and SPKTx. A total of 59 patients participated in the study, all of whom were candidates for KTx-23 or SPKTx-36. The study population consisted of 35 women (W) and 24 men (M), with an overall mean age of 44.8 ± 10.2 years (43.5 ± 10.2 years for W and 46.2 ± 10.9 years for M). Both groups included patients on hemodialysis (n = 34) and peritoneal dialysis (n = 12), and patients in the predialysis period (pre-emptive, n = 13). The examined parameters included Onodera's prognostic nutritional index (PNIO), the nutritional risk index (NRI), proper body mass calculated using the Lorenz formula, and the neutrophil-to-lymphocyte ratio (NLR). All patients were assessed according to the NRS 2002 scale. RESULTS Analysis of the obtained results revealed that the NLR was only one differentiating parameter between Ktx and SPKtx group. Multivariate analysis adjusted for patients' age and gender, comparing quantitative NS indicators was performed. Albumin serum concentration was not dependent on patients' group (KTx/SPKTx) neither age nor gender P = .382. BMI was dependent on patients' age and gender, but not a group (KTx/SPKTx) P = .008. PNIO, NRI, and NRL were not dependent on patients' group (KTx/SPKTx) neither age nor gender. CONCLUSIONS Additional effort should be devoted to the development of a proper nutrition plan for SPKTx a especially in peritoneal dialysis patients. Toward patients on the waiting list, the regular assessment of nutritional status should be performed which is not a rule in dialysis centers. SPKTx candidates in the perioperative period should receive proper nutrition taking into account their caloric and protein needs.
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Affiliation(s)
- Karolina Kędzierska-Kapuza
- Department of Gastroenterological Surgery and Transplantology, Centre of Postgraduate Medical Education, Warsaw, Poland.
| | - Krzysztof Safranow
- Independent Laboratory of Biostatistics, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Kacper Niewiński
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of the Ministry of Interior Affairs and Administration, Warsaw, Poland
| | - Grzegorz Niewiński
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of the Ministry of Interior Affairs and Administration, Warsaw, Poland
| | - Marek Durlik
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of the Ministry of Interior Affairs and Administration, Warsaw, Poland
| | - Małgorzata Szczuko
- Department of Human Nutrition and Metabolomic, Pomeranian Medical University in Szczecin, Szczecin, Poland.
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Zheng X, Xue Q, Wang Y, Lu L, Pan Y, Xu J, Zhang J. A. officinarum Hance - P. cablin (Blanco) Benth drug pair improves oxidative stress, intracellular Ca 2+ concentrations and apoptosis by inhibiting the AGE/RAGE axis to ameliorate diabetic gastroparesis: In vitro and in vivo studies. JOURNAL OF ETHNOPHARMACOLOGY 2024; 324:117832. [PMID: 38280660 DOI: 10.1016/j.jep.2024.117832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 01/24/2024] [Indexed: 01/29/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Alpinia officinarum Hance is a perennial natural medicine herbivorous plant, has been used in the management of treat stomach pain and diabetes, it is abundantly cultivated in Qiongzhong, Baisha and other places. P. cablin (Blanco) Benth, one of the most important traditional Chinese plants, which plays functions in antioxidant and gastrointestinal regulation, has been extensively planted in Hainan, Guangdong and other regions. AIM OF THE STUDY In this study, we investigated the role and underlying molecular mechanism of AP on diabetic gastroparesis (DGP) in vitro and in vivo. MATERIALS AND METHODS In this study, using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum Hance-P. cablin (Blanco) Benth drug pair (AP). Molecular docking were utilized to explore the potential mechanism of AP treatment of DGP. In in vitro assays, gastric smooth muscle cells (GSMCs) were treated with 35 mM glucose to promote apoptosis and construct the DGP model, which was treated with different concentrations of AP. Furthermore, transfection technology was used to overexpress RAGE in GSMCs and elucidate the underlying mechanisms of alleviation of DGP by AP. RESULTS Using UPLC-MS/MS analysis, nine components of AP were identified. We found that AP effectively blocked the increase in apoptosis, oxidative stress, and intracellular Ca2+ concentrations. For in vivo experiments, mice were fed with a high-fat irregular diet to construct DGP model, and AP was co-administered via oral gavage daily to prevent the development of DGP. Compared with DGP mice, AP significantly decreased fasting blood glucose levels and increased gastric emptying levels. Consistent with in vitro experiments, AP also considerably decreased the increase in oxidative stress in DGP mice. Mechanistically, AP alleviates apoptosis and DGP by decreasing oxidative stress and intracellular Ca2+ concentrations via the inhibition of the AGE/RAGE axis. CONCLUSIONS Collectively, this study has established that AP can improve DGP, and the mechanism may be related to the inhibition the AGE/RAGE axis to mitigate apoptosis and DGP. To summarize, this study provides a novel supplementary strategy for DGP treatment.
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Affiliation(s)
- Xiuwen Zheng
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
| | - Qianrong Xue
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
| | - Yinghuan Wang
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
| | - Lu Lu
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
| | - Yipeng Pan
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
| | - Jian Xu
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
| | - Junqing Zhang
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory of R & D on Tropical Herbs, Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hepatobiliary and Liver Transplantation Department of Hainan Digestive Disease Center of The Second Affiliated Hospital of Hainan Medical University, Engineering Research Center of Tropical Medicine of Ministry of Education, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
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Yagyu T, Yakami Y, Bando T. Acute gastric dilatation with segmented abdominal paresis as a rare manifestation of herpes zoster: a case report and review of the literature. J Med Case Rep 2024; 18:165. [PMID: 38584287 PMCID: PMC11000452 DOI: 10.1186/s13256-024-04487-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 03/01/2024] [Indexed: 04/09/2024] Open
Abstract
BACKGROUND Herpes zoster is a common disease that can affect men and women at any age. Sensory neuropathy is the most common complication while motor neuropathy of the abdominal muscles is rare complication appearing in ~ 0.7% of patients. Furthermore, visceral nerve involvement causing gastroparesis is an extremely rare postherpetic complication. We present an extremely rare case of acute gastric dilatation with segmented abdominal paresis as a rare manifestation of herpes zoster infection. CASE PRESENTATION A 91-year-old Asian man was admitted to hospital with 2-day history of vomiting and left abdominal protrusion. He was previously treated for a rash on the left abdominal wall as herpes zoster infection with oral valaciclovir 2 weeks prior. On physical examination, characteristic herpes zoster rash scars and an ipsilateral abdominal bulge were observed on the left side. Computed tomography revealed no abdominal wall defect, mass, or stenosis. Remarkable distension of the stomach, asymmetrical left flank wall bulge, and a thinner abdominal wall on the left compared with the right side were shown. He was diagnosed as acute gastric dilatation owing to gastroparesis and segmental paresis of the abdominal musculature associated with herpes zoster infection. The patient showed significant improvement in symptoms and abdominal paresis within a month of conservative treatment, including nasogastric tube decompression and mosapride administration. CONCLUSION Acute gastric dilatation with abdominal paresis is an extremely rare complication of herpes zoster infection, and to date there have been no reports in the literature. It alerts us that, when examining patients with abdominal bulge, we should be conscious of this rare pathology for the optical diagnosis, avoiding unnecessary invasive examination or surgical exploration.
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Affiliation(s)
- Toshihiko Yagyu
- Department of Gastroenterology, Higashi Osaka Hospital, 1-7-22, Chuo, Jyoto-Ku, Osaka, 536-0005, Japan.
| | - Yoshikazu Yakami
- Department of Gastroenterology, Higashi Osaka Hospital, 1-7-22, Chuo, Jyoto-Ku, Osaka, 536-0005, Japan
| | - Tomoki Bando
- Department of Gastroenterology, Higashi Osaka Hospital, 1-7-22, Chuo, Jyoto-Ku, Osaka, 536-0005, Japan
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Perlas A, Xiao MZX, Tomlinson G, Jacob B, Abdullah S, Kruisselbrink R, Chan VWS. Baseline Gastric Volume in Fasting Diabetic Patients Is Not Higher than That in Nondiabetic Patients: A Cross-sectional Noninferiority Study. Anesthesiology 2024; 140:648-656. [PMID: 37883294 DOI: 10.1097/aln.0000000000004815] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]
Abstract
BACKGROUND The physiology of diabetes mellitus can increase the risk of perioperative aspiration, but there is limited and contradictory evidence on the incidence of "full stomach" in fasting diabetic patients. The aim of this study is to assess the baseline gastric content (using gastric ultrasound) in diabetic and nondiabetic patients scheduled for elective surgery who have followed standard preoperative fasting instructions. METHODS This was a prospective, noninferiority study of 180 patients (84 diabetic and 96 nondiabetic patients). Bedside ultrasound was used for qualitative and quantitative assessment of the gastric antrum in the supine and right lateral decubitus positions. Fasting gastric volume was estimated based on the cross-sectional area of the gastric antrum and a validated model. The hypothesis was that diabetic patients would not have a higher baseline fasting gastric volume compared to nondiabetic patients, with a noninferiority margin of 0.4 ml/kg. Secondary aims included the comparison of the incidence of full stomach (solid content or more than 1.5 mL/kg of clear fluid), estimation of the 95th percentile of the gastric volume distribution in both groups, and examination of the association between gastric volume, glycemic control, and diabetic comorbidities. RESULTS The baseline gastric volume was not higher in diabetic patients (0.81 ± 0.61 ml/kg) compared to nondiabetic patients (0.87 ± 0.53 ml/kg) with a mean difference of -0.07 ml/kg (95% CI, -0.24 to 0.10 ml/kg). A total of 13 (15.5%) diabetic and 11 (11.5%) nondiabetic patients presented more than 1.5 ml/kg of gastric volume (95% CI for difference, -7.1 to 15.2%). There was little correlation between the gastric volume and either the time since diagnosis or HbA1C. CONCLUSIONS The data suggest that the baseline gastric volume in diabetic patients who have followed standard fasting instructions is not higher than that in nondiabetic patients. EDITOR’S PERSPECTIVE
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Affiliation(s)
- Anahi Perlas
- Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada; and Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | | | - George Tomlinson
- Biostatistical Research Unit, University Health Network, Toronto, Ontario, Canada
| | - Binu Jacob
- Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | - Sara Abdullah
- Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada
| | | | - Vincent W S Chan
- Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
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Lombardo F, Bombaci B, Costa S, Valenzise M, Giannitto N, Cardile D, Baldari S, Salzano G, Passanisi S. Gastroparesis in Adolescent Patient with Type 1 Diabetes: Severe Presentation of a Rare Pediatric Complication. J Clin Res Pediatr Endocrinol 2024; 16:111-115. [PMID: 36047486 PMCID: PMC10938516 DOI: 10.4274/jcrpe.galenos.2022.2022-5-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/25/2022] [Indexed: 12/01/2022] Open
Abstract
Gastroparesis is a long-term complication of diabetes related to autonomic neuropathy. It is characterized clinically by delayed gastric emptying and upper gastrointestinal symptoms, including early satiety, postprandial fullness, nausea, vomiting, and abdominal pain. Gastric emptying scintigraphy is the gold standard for diagnosis as it reveals delayed gastric emptying. Therapeutic strategies include dietary modifications, improvement of glycemic control, and prokinetic drugs. Case descriptions of diabetic gastroparesis in pediatric ages are very scarce. We report the case of a 16-year-old adolescent with severe presentation of diabetic gastroparesis. She presented with recurrent episodes of nausea, vomiting and abdominal pain which led progressively to reduced oral intake and weight loss. Her past glycemic control had been quite brittle, as demonstrated by several hospitalizations due to diabetic ketoacidosis and recurrent episodes of severe hypoglycemia. After the exclusion of infectious, mechanical, metabolic, and neurological causes of vomiting, a gastric emptying scintigraphy was performed, leading to the diagnosis of gastroparesis. Treatment with metoclopramide was started with progressive relief of symptoms. To improve glycemic control, insulin therapy with an advanced hybrid, closed loop system was successfully started. Pediatricians should consider diabetic gastroparesis in children and adolescents with long-standing, poorly controlled diabetes and appropriate symptomology.
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Affiliation(s)
- Fortunato Lombardo
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Messina, Italy
| | - Bruno Bombaci
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Messina, Italy
| | - Stefano Costa
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Pediatric Gastroenterology and Cystic Fibrosis Unit, Messina, Italy
| | - Mariella Valenzise
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Messina, Italy
| | - Nino Giannitto
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Messina, Italy
| | - Davide Cardile
- University of Messina, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Messina, Italy
| | - Sergio Baldari
- University of Messina, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Messina, Italy
| | - Giuseppina Salzano
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Messina, Italy
| | - Stefano Passanisi
- University of Messina, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Messina, Italy
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Uppaluri S, Jain MA, Ali H, Shingala J, Amin D, Ajwani T, Fatima I, Patel N, Kaka N, Sethi Y, Kapoor N. Pathogenesis and management of diabetic gastroparesis: An updated clinically oriented review. Diabetes Metab Syndr 2024; 18:102994. [PMID: 38579489 DOI: 10.1016/j.dsx.2024.102994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 02/25/2024] [Accepted: 03/20/2024] [Indexed: 04/07/2024]
Abstract
BACKGROUND AND AIMS Diabetic gastroparesis (DGp) is a common and preventable complication of uncontrolled diabetes mellitus (D.M.) and significantly affects the Quality of Life of patients. Diagnosis and management present as a clinical challenge due to the disease's complexity and limited effective therapeutic options. This review aims to comprehensively outline the pathogenesis, diagnosis, and management of diabetic gastroparesis, evaluating evolving approaches to guide clinicians and provide future recommendations. METHODS A literature review was conducted on scholarly databases of PubMed, Google Scholar, Scopus and Web of Science encompassing published articles, gray literature and relevant clinical guidelines. Data were synthesized and analyzed to provide a comprehensive overview of diabetic gastroparesis, focusing on pathogenesis, diagnosis, and management. RESULTS The review intricately explores the pathogenesis contributing to diabetic gastroparesis, emphasizing autonomic neuropathy, oxidative stress, inflammation, hormonal dysregulation, microbiota alterations, and gastrointestinal neuropathy. Primary management strategies are underscored, including lifestyle modifications, symptom relief, and glycemic control. The discussion encompasses pharmacological and surgical options, highlighting the importance of a multidisciplinary approach involving various healthcare professionals for comprehensive patient care. CONCLUSION This review offers a thorough understanding of pathogenesis, diagnosis, and management of diabetic gastroparesis, underlining evolving approaches for clinicians. A multidisciplinary approach is crucial to address both the physical and mental health aspects of diabetes and its complications.
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Affiliation(s)
- Srikar Uppaluri
- Kamineni Academy of Medical Sciences and Research Center, Hyderabad, India; PearResearch, Dehradun, India.
| | - Manisha Ashok Jain
- PearResearch, Dehradun, India; Shri Bhausaheb Hire Govt. Medical College, Dhule, Maharashtra, India.
| | - Hira Ali
- PearResearch, Dehradun, India; Chifeng University Medical College, China.
| | - Jay Shingala
- PearResearch, Dehradun, India; B.J. Medical College, Ahmedabad, India.
| | - Dhruti Amin
- PearResearch, Dehradun, India; GMERS Medical College and Hospital, Gotri, Vadodara, India.
| | - Trisha Ajwani
- PearResearch, Dehradun, India; Baroda Medical College, Gujarat, India.
| | - Irum Fatima
- PearResearch, Dehradun, India; Osmania Medical College, Hyderabad, India.
| | - Neil Patel
- PearResearch, Dehradun, India; GMERS Medical College, Himmatnagar, Gujarat, India.
| | - Nirja Kaka
- PearResearch, Dehradun, India; GMERS Medical College, Himmatnagar, Gujarat, India.
| | - Yashendra Sethi
- PearResearch, Dehradun, India; Government Doon Medical College, Dehradun, India.
| | - Nitin Kapoor
- Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India.
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Cao J, Zhou X, Yan H, Li L. Application of acupuncture in diabetic gastroparesis: A case series. Asian J Surg 2024; 47:1401-1402. [PMID: 38036355 DOI: 10.1016/j.asjsur.2023.11.100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 11/17/2023] [Indexed: 12/02/2023] Open
Affiliation(s)
- Jianzhi Cao
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, People's Republic of China
| | - Xia Zhou
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, People's Republic of China
| | - Hui Yan
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, People's Republic of China
| | - Liuying Li
- Traditional Chinese Medicine Department, Zigong First People's Hospital, Zigong, People's Republic of China; Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
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Fan X, Liu Y, Li S, Yang Y, Zhao Y, Li W, Hao J, Xu Z, Zhang B, Liu W, Zhang S. Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases. Heliyon 2024; 10:e26270. [PMID: 38375243 PMCID: PMC10875596 DOI: 10.1016/j.heliyon.2024.e26270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 02/08/2024] [Accepted: 02/09/2024] [Indexed: 02/21/2024] Open
Abstract
The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the "molecular-cellular" mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.
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Affiliation(s)
- Xiaojing Fan
- The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300250, China
| | - Yunlong Liu
- Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Shanshan Li
- Research Center of Experimental Acupuncture Science, Tianjin University of Chinese Medicine, Tianjin, 301617, China
| | - Yongrui Yang
- Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Yinghui Zhao
- Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Wenxi Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Jiaxin Hao
- Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Zhifang Xu
- Research Center of Experimental Acupuncture Science, Tianjin University of Chinese Medicine, Tianjin, 301617, China
| | - Bo Zhang
- Department of Automation, Tsinghua University, Institute for TCM-X, Beijing, 100084, China
| | - Wei Liu
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Hebei Province Hospital of Chinese Medicine, Hebei Shijiazhuang, 050011, China
| | - Suzhao Zhang
- The First Affiliated Hospital of Hebei University of Chinese Medicine, Hebei Province Hospital of Chinese Medicine, Hebei Shijiazhuang, 050011, China
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Yuan HL, Zhang X, Chu WW, Lin GB, Xu CX. Risk factor analysis and nomogram for predicting gastroparesis in patients with type 2 diabetes mellitus. Heliyon 2024; 10:e26221. [PMID: 38390180 PMCID: PMC10881375 DOI: 10.1016/j.heliyon.2024.e26221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 02/06/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Purpose The incidence of gastroparesis is higher in individuals diagnosed with type 2 diabetes mellitus (T2DM) compared to the healthy individuals. Our study aimed to explore the risk factors for gastroparesis in T2DM and to establish a clinical prediction model (nomogram). Methods Our study enlisted 694 patients with T2DM from two medical centers over a period of time. From January 2020 to December 2022, 347 and 149 patients were recruited from the Beilun branch of Zhejiang University's First Affiliated Hospital in the training and internal validation cohorts, respectively. The external validation cohort consisted of 198 patients who were enrolled at Nanchang University's First Affiliated Hospital from October 2020 to September 2021. We conducted univariate and multivariate logistic regression analyses to select the risk factors for gastroparesis in patients with T2DM; subsequently,we developed a nomogram model. The performance of the nomogram was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis(DCA). Results Four clinical variables, including age, regular exercise, glycated hemoglobin level(HbA1c), and Helicobacter pylori (H. pylori) infection, were identified and included in the model. The model demonstrated excellent discrimination, with an AUC of 0.951 (95% CI = 0.925-0.978) in the training group, and 0.910 (95% CI = 0.859-0.961) and 0.875 (95% CI = 0.813-0.937) in the internal and external validation groups, respectively. The calibration curve showed good consistency between prediction of the model and observed gastroparesis. The DCA also demonstrated good clinical efficacy. Conclusion The nomogram model developed in this study showed good performance in predicting gastroparesis in patients with T2DM.
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Affiliation(s)
- Hai-Liang Yuan
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, China
- The Precision Medicine Laboratory, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, China
| | - Xian Zhang
- Department of Endocrinology, the First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Wei-Wei Chu
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, China
| | - Guan-Bin Lin
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, China
| | - Chun-Xia Xu
- Department of Gastroenterology, Beilun Branch of the First Affiliated Hospital of Zhejiang University, Ningbo, China
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Caturano A, Cavallo M, Nilo D, Vaudo G, Russo V, Galiero R, Rinaldi L, Marfella R, Monda M, Luca G, Sasso FC. Diabetic Gastroparesis: Navigating Pathophysiology and Nutritional Interventions. GASTROINTESTINAL DISORDERS 2024; 6:214-229. [DOI: 10.3390/gidisord6010016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Diabetic gastroparesis (DGP) delays gastric emptying in diabetes patients, notably impacting those with type 1 and long-standing type 2 diabetes. Symptoms include early satiety, fullness, appetite loss, bloating, abdominal pain, and vomiting, arising from slow stomach-to-intestine food movement. DGP’s unpredictable nature complicates diagnosis and blood glucose management, leading to severe complications like dehydration, malnutrition, and bezoar formation. Understanding DGP’s mechanisms is crucial for effective management. Vagal dysfunction, disturbances in the interstitial cells of Cajal, reduced neural nitric oxide synthase, and increased oxidative stress contribute to the complex pathophysiology. Accurate diagnosis demands a comprehensive approach, utilizing tools like gastric scintigraphy and the Gastric Emptying Breath Test. Considering the complex relationship between DGP and glycemia, managing blood glucose levels becomes paramount. Nutritional interventions, tailored to each patient, address malnutrition risks, emphasizing smaller, more frequent meals and liquid consistency. DGP’s complex nature necessitates collaborative efforts for enhanced diagnostic strategies, improved pathophysiological understanding, and compassionate management approaches. This comprehensive approach offers hope for a future where individuals with DGP can experience improved well-being and quality of life.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Massimiliano Cavallo
- Internal Medicine Unit, Santa Maria Terni Hospital, I-05100 Terni, Italy
- Medical Andrology and Reproductive Endocrinology Unit, Santa Maria Hospital, I-05100 Terni, Italy
| | - Davide Nilo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Gaetano Vaudo
- Internal Medicine Unit, Santa Maria Terni Hospital, I-05100 Terni, Italy
| | - Vincenzo Russo
- Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Luca Rinaldi
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, University of Molise, I-86100 Campobasso, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Marcellino Monda
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
| | - Giovanni Luca
- Medical Andrology and Reproductive Endocrinology Unit, Santa Maria Hospital, I-05100 Terni, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, I-80138 Naples, Italy
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Zhang S, Zhang C, Fan M, Chen T, Yan H, Shi N, Chen Y. Neuromodulation and Functional Gastrointestinal Disease. Neuromodulation 2024; 27:243-255. [PMID: 37690016 DOI: 10.1016/j.neurom.2023.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 07/10/2023] [Accepted: 08/03/2023] [Indexed: 09/11/2023]
Abstract
INTRODUCTION Functional gastrointestinal disorders (FGIDs) are common, and they severely impair an individual's quality of life. The mechanism of pathogenesis and the effective treatments for FGIDs remain elusive. Neuromodulation-a relatively new treatment-has exhibited a good therapeutic effect on FGIDs, although there are different methods for different symptoms of FGIDs. MATERIALS AND METHODS We used PubMed to review the history of neuromodulation for the treatment of FGIDs and to review several recently proposed neuromodulation approaches with improved effects on FGIDs. CONCLUSION Electroacupuncture, transcutaneous electroacupuncture, transcutaneous auricular vagal nerve stimulation, sacral nerve stimulation (SNS) (which relies on vagal nerve stimulation), and gastric electrical stimulation (which works through the modulation of slow waves generated by the interstitial cells of Cajal), in addition to the noninvasive neurostimulation alternative approach method of SNS-tibial nerve stimulation and transcutaneous electrical stimulation (which is still in its infancy), are some of the proposed neuromodulation approaches with improved effects on FGIDs. This review has discussed some critical issues related to the selection of stimulation parameters and the underlying mechanism and attempts to outline future research directions backed by the existing literature.
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Affiliation(s)
- Shuhui Zhang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Can Zhang
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Mingwei Fan
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Tan Chen
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Hui Yan
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Ning Shi
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Yan Chen
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China.
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Madhu SV, Raizada N. Starving for a Cure. Indian J Endocrinol Metab 2024; 28:1-2. [PMID: 38533290 PMCID: PMC10962772 DOI: 10.4103/ijem.ijem_63_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2024] Open
Affiliation(s)
- S V Madhu
- Department of Endocrinology, Centre for Diabetes Endocrinology and Metabolism, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India
| | - Nishant Raizada
- Department of Endocrinology, Centre for Diabetes Endocrinology and Metabolism, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India
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Joshi GP. Anesthetic Considerations in Adult Patients on Glucagon-Like Peptide-1 Receptor Agonists: Gastrointestinal Focus. Anesth Analg 2024; 138:216-220. [PMID: 37874648 DOI: 10.1213/ane.0000000000006810] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2023]
Affiliation(s)
- Girish P Joshi
- From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas
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Kamp J, Zwart TC, Meziyerh S, van der Boog PJM, Nijgh EE, van Duin K, de Vries APJ, Moes DJAR. Meltdose Tacrolimus Population Pharmacokinetics and Limited Sampling Strategy Evaluation in Elderly Kidney Transplant Recipients. Pharmaceutics 2023; 16:17. [PMID: 38276495 PMCID: PMC10819724 DOI: 10.3390/pharmaceutics16010017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/17/2023] [Accepted: 12/19/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Meltdose tacrolimus (Envarsus®) has been marketed as a formulation achieving a more consistent tacrolimus exposure. Due to the narrow therapeutic window of tacrolimus, dose individualization is essential. Relaxation of the upper age limits for kidney transplantations has resulted in larger numbers of elderly patients receiving tacrolimus. However, due to the physiological changes caused by aging, the tacrolimus pharmacokinetics (PK) might be altered. The primary aim was to develop a population PK model in elderly kidney transplant recipients. Secondary aims were the development and evaluation of a limited sampling strategy (LSS) for AUC estimation. METHODS A total of 34 kidney transplant recipients aged ≥65 years, starting on meltdose tacrolimus directly after transplantation, were included. An eight-point whole blood AUC0-24h and an abbreviated dried blood spot (DBS) AUC0-24h were obtained. The PK data were analyzed using nonlinear mixed effect modeling methods. RESULTS The PK data were best described using a two-compartment model, including three transit compartments and a mixture model for oral absorption. The best three-sample LSS was T = 0, 2, 6 h. The best four-sample LSSs were T = 0, 2, 6, 8 h and T = 0, 1, 6, 8 h. CONCLUSIONS The developed population PK model adequately described the tacrolimus PK data in a population of elderly kidney transplant recipients. In addition, the developed population PK model and LSS showed an adequate estimation of tacrolimus exposure, and may therefore be used to aid in tacrolimus dose individualization.
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Affiliation(s)
- Jasper Kamp
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (J.K.); (T.C.Z.)
| | - Tom C. Zwart
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (J.K.); (T.C.Z.)
| | - Soufian Meziyerh
- Transplant Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.M.); (A.P.J.d.V.)
- Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Paul J. M. van der Boog
- Transplant Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.M.); (A.P.J.d.V.)
- Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Esther E. Nijgh
- Transplant Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.M.); (A.P.J.d.V.)
- Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Koen van Duin
- Transplant Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.M.); (A.P.J.d.V.)
- Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Aiko P. J. de Vries
- Transplant Center, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (S.M.); (A.P.J.d.V.)
- Division of Nephrology, Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Dirk Jan A. R. Moes
- Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; (J.K.); (T.C.Z.)
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Gao F, Hayashi Y, Saravanaperumal SA, Gajdos GB, Syed SA, Bhagwate AV, Ye Z, Zhong J, Zhang Y, Choi EL, Kvasha SM, Kaur J, Paradise BD, Cheng L, Simone BW, Wright AM, Kellogg TA, Kendrick ML, McKenzie TJ, Sun Z, Yan H, Yu C, Bharucha AE, Linden DR, Lee JH, Ordog T. Hypoxia-Inducible Factor 1α Stabilization Restores Epigenetic Control of Nitric Oxide Synthase 1 Expression and Reverses Gastroparesis in Female Diabetic Mice. Gastroenterology 2023; 165:1458-1474. [PMID: 37597632 PMCID: PMC10840755 DOI: 10.1053/j.gastro.2023.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 07/18/2023] [Accepted: 08/09/2023] [Indexed: 08/21/2023]
Abstract
BACKGROUND & AIMS Although depletion of neuronal nitric oxide synthase (NOS1)-expressing neurons contributes to gastroparesis, stimulating nitrergic signaling is not an effective therapy. We investigated whether hypoxia-inducible factor 1α (HIF1A), which is activated by high O2 consumption in central neurons, is a Nos1 transcription factor in enteric neurons and whether stabilizing HIF1A reverses gastroparesis. METHODS Mice with streptozotocin-induced diabetes, human and mouse tissues, NOS1+ mouse neuroblastoma cells, and isolated nitrergic neurons were studied. Gastric emptying of solids and volumes were determined by breath test and single-photon emission computed tomography, respectively. Gene expression was analyzed by RNA-sequencing, microarrays, immunoblotting, and immunofluorescence. Epigenetic assays included chromatin immunoprecipitation sequencing (13 targets), chromosome conformation capture sequencing, and reporter assays. Mechanistic studies used Cre-mediated recombination, RNA interference, and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated epigenome editing. RESULTS HIF1A signaling from physiological intracellular hypoxia was active in mouse and human NOS1+ myenteric neurons but reduced in diabetes. Deleting Hif1a in Nos1-expressing neurons reduced NOS1 protein by 50% to 92% and delayed gastric emptying of solids in female but not male mice. Stabilizing HIF1A with roxadustat (FG-4592), which is approved for human use, restored NOS1 and reversed gastroparesis in female diabetic mice. In nitrergic neurons, HIF1A up-regulated Nos1 transcription by binding and activating proximal and distal cis-regulatory elements, including newly discovered super-enhancers, facilitating RNA polymerase loading and pause-release, and by recruiting cohesin to loop anchors to alter chromosome topology. CONCLUSIONS Pharmacologic HIF1A stabilization is a novel, translatable approach to restoring nitrergic signaling and treating diabetic gastroparesis. The newly recognized effects of HIF1A on chromosome topology may provide insights into physioxia- and ischemia-related organ function.
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Affiliation(s)
- Fei Gao
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Gastroenterology, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Yujiro Hayashi
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Siva Arumugam Saravanaperumal
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Gabriella B Gajdos
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Sabriya A Syed
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota
| | - Aditya V Bhagwate
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Zhenqing Ye
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Jian Zhong
- Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota
| | - Yuebo Zhang
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Egan L Choi
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Sergiy M Kvasha
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Jagneet Kaur
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Brooke D Paradise
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota
| | - Liang Cheng
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Brandon W Simone
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota
| | - Alec M Wright
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota
| | - Todd A Kellogg
- Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | | | | | - Zhifu Sun
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota
| | - Huihuang Yan
- Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota
| | - Chuanhe Yu
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - David R Linden
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota
| | - Jeong-Heon Lee
- Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota; Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Tamas Ordog
- Enteric NeuroScience Program and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Gastroenterology Research Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
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Chen C, Beloqui A, Xu Y. Oral nanomedicine biointeractions in the gastrointestinal tract in health and disease. Adv Drug Deliv Rev 2023; 203:115117. [PMID: 37898337 DOI: 10.1016/j.addr.2023.115117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/03/2023] [Accepted: 10/21/2023] [Indexed: 10/30/2023]
Abstract
Oral administration is the preferred route of administration based on the convenience for and compliance of the patient. Oral nanomedicines have been developed to overcome the limitations of free drugs and overcome gastrointestinal (GI) barriers, which are heterogeneous across healthy and diseased populations. This review aims to provide a comprehensive overview and comparison of the oral nanomedicine biointeractions in the gastrointestinal tract (GIT) in health and disease (GI and extra-GI diseases) and highlight emerging strategies that exploit these differences for oral nanomedicine-based treatment. We introduce the key GI barriers related to oral delivery and summarize their pathological changes in various diseases. We discuss nanomedicine biointeractions in the GIT in health by describing the general biointeractions based on the type of oral nanomedicine and advanced biointeractions facilitated by advanced strategies applied in this field. We then discuss nanomedicine biointeractions in different diseases and explore how pathological characteristics have been harnessed to advance the development of oral nanomedicine.
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Affiliation(s)
- Cheng Chen
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium
| | - Ana Beloqui
- UCLouvain, Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, 1200 Brussels, Belgium; WEL Research Institute, avenue Pasteur, 6, 1300 Wavre, Belgium.
| | - Yining Xu
- Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
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Zhou L, Lian H, Yin Y, Zheng YS, Han YX, Liu GQ, Wang ZY. New insights into muscularis macrophages in the gut: from their origin to therapeutic targeting. Immunol Res 2023; 71:785-799. [PMID: 37219708 DOI: 10.1007/s12026-023-09397-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 05/15/2023] [Indexed: 05/24/2023]
Abstract
Muscularis macrophages, as the most abundant immune cells in the intestinal muscularis externa, exhibit tissue protective phenotype in the steady state. Owing to tremendous advances in technology, we now know the fact that muscularis macrophages are a heterogeneous population of cells which could be divided into different functional subsets depending on their anatomic niches. There is emerging evidence showing that these subsets, through molecular interactions with their neighbours, take part in a wide range of physiological and pathophysiological processes in the gut. In this review, we summarize recent progress (particularly over the past 4 years) on distribution, morphology, origin and functions of muscularis macrophages and, where possible, the characteristics of specific subsets in response to the microenvironment they occupy, with particular emphasis on their role in muscular inflammation. Furthermore, we also integrate their role in inflammation-related gastrointestinal disorders, such as post-operative ileus and diabetic gastroparesis, in order to propose future therapeutic strategies.
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Affiliation(s)
- Li Zhou
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
- Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang, 453003, China
| | - Hui Lian
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
- Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang, 453003, China
| | - Yue Yin
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Yuan-Sheng Zheng
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Yu-Xin Han
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Gao-Qi Liu
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Zhi-Yong Wang
- Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.
- Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang, 453003, China.
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Li M, Gao N, Wang S, Guo Y, Liu Z. A global bibliometric and visualized analysis of the status and trends of gastroparesis research. Eur J Med Res 2023; 28:543. [PMID: 38017518 PMCID: PMC10683151 DOI: 10.1186/s40001-023-01537-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Accepted: 11/17/2023] [Indexed: 11/30/2023] Open
Abstract
BACKGROUND Gastroparesis has a substantial impact on the quality of life but has limited treatment options, which makes it a public health concern. No bibliometric studies on gastroparesis have been published thus far. Thus, this article aims to summarize and analyze research hotspots to provide a reference for clinical researchers. MATERIALS AND METHODS Gastroparesis-related research articles were searched in the Web of Science Core Collection (WOSCC), and relevant information was extracted after screening. A total of 1033 documents were analyzed with the bibliometric method using Microsoft Excel, Citespace, and VOSviewer. RESULTS Overall, our search retrieved 1033 papers contributed by 966 research institutions from 53 countries. Since 1980, publications in this field have increased rapidly. United States (n = 645) and Temple University (n = 122) were the most productive country and institution, respectively. Parkman, with 96 publications, was the most prominent author. CONCLUSIONS Research hotspots in gastroparesis can be summarized into four domains: innovation in diagnostic modalities, change of oral therapeutic agents, choice of surgical interventions, and pathological mechanisms. Future research on gastroparesis should focus on the quality of life of patients, diagnostic techniques, pyloromyotomy, and transpyloric stent placement.
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Affiliation(s)
- Meng Li
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China
| | - Ning Gao
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China
| | - Shaoli Wang
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China
| | - Yufeng Guo
- Department of Acupuncture and Moxibustion, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China.
| | - Zhen Liu
- Department of Gastroenterology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5 Beixiange St., Xicheng District, Beijing, 100053, China.
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Li X, Ji S, Cipriani G, Hillestad ML, Eisenman ST, Barry MA, Nath KA, Linden DR, Wright A, AlAsfoor S, Grover M, Sha L, Hsi LC, Farrugia G. Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice. Neurogastroenterol Motil 2023; 35:e14669. [PMID: 37702100 PMCID: PMC10841310 DOI: 10.1111/nmo.14669] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 06/07/2023] [Accepted: 08/14/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE. METHODS C57BL6 diabetic delayed GE mice were injected with 1 × 1012 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [13 C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression. KEY RESULTS Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE. CONCLUSIONS AND INFERENCES Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.
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Affiliation(s)
- Xiaojie Li
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China
| | - Sihan Ji
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China
| | - Gianluca Cipriani
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
| | | | - Seth T. Eisenman
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
| | - Michael A. Barry
- Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, Mn, USA
| | - Karl A. Nath
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
- Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Mn, USA
| | - David R. Linden
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
| | - Alec Wright
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
| | - Shefaa AlAsfoor
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
| | - Madhusudan Grover
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
| | - Lei Sha
- Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning Province, China
| | - Linda C. Hsi
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
| | - Gianrico Farrugia
- Department of Medicine, Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Mn, USA
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Inoue S, Yasuda H, Takashi K, Okamoto H. A Type 2 Diabetes Mellitus Patient With Severe Diabetic Gastroparesis Successfully Treated With Intravenous Erythromycin. Cureus 2023; 15:e49075. [PMID: 38125242 PMCID: PMC10731627 DOI: 10.7759/cureus.49075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 12/23/2023] Open
Abstract
Gastroparesis, characterized by a decrease in gastric emptying, can lead to worsened diabetes control and a reduced quality of life. The patient was a 32-year-old male with type 2 diabetes. He was initially admitted for control of diabetes, and two months later, he was readmitted due to nausea and vomiting. He showed resistance to various drugs, including antiemetics, and an upper gastrointestinal endoscopy revealed significant gastric residue, leading to a diagnosis of gastroparesis. We administered intravenous erythromycin. After three days of treatment, the vomiting resolved. Gastroparesis is challenging to manage, and there are limited effective treatment options. We experienced a case of diabetic gastroparesis with severe vomiting and loss of appetite that responded remarkably well to intravenous erythromycin treatment. Intravenous administration of erythromycin may be a potentially effective treatment for gastroparesis.
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Affiliation(s)
- Saori Inoue
- Internal Medicine, Meitetsu Hospital, Nagoya, JPN
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50
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Mizerska A, Durlik M, Kędzierska-Kapuza K. Nutritional Risk of Candidates for Simultaneous Pancreatic-Kidney Transplantation-A Narrative Review. Nutrients 2023; 15:4179. [PMID: 37836461 PMCID: PMC10574362 DOI: 10.3390/nu15194179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/14/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
INTRODUCTION Not much is known about the significance of nutritional status and support in transplant surgery, least of all in simultaneous pancreatic and kidney transplantation. Malnutrition in the context of simultaneous pancreatic-kidney transplantation seems to be complex and a still poorly investigated problem. Since SPKTX is highly qualified and also has a small volume procedure, it is difficult to obtain data from large cohorts of patients. The aim of this article is to gather existing evidence and information about the subject, as well as to elicit some questions and goals for the future. METHODS We searched through the Pub-Med database using the keywords "pancreas and kidney transplantation" combined with "nutritional risk", "nutritional status", "malnutrition", "nutritional intervention", and "frailty", finding a total of 4103 matching results. We then narrowed it down to articles written in English with the full text available. We also researched through the references of articles most accurately matching our researched terms. RESULTS There are numerous tools that have been investigated for the screening of malnutrition, such as the NRI index, PNI index, NLR, SGA scale, and NRS-2002 scale, each of which proved to be of some use in predicting patient outcomes in different surgical settings. Since all of them differed in components and assessed parameters and, in the absence of more sensitive or infallible indicators, the most reasonable approach seems to evaluate them jointly. CONCLUSION It is important to underline the necessity of nutritional screening and the subsequent introduction of adequate therapy while awaiting transplantation in an attempt to improve results. Considering the complexity of surgical procedures and the severity of underlying diseases with their intense metabolic components, the patient's nutritional status seems to significantly influence results. Consequently, nutritional risk assessments should be a part of the routine care of patients qualified for transplantation.
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Affiliation(s)
- Agnieszka Mizerska
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of the Ministry of Interior Affairs and Administration, Wołoska St. 137, 02-507 Warsaw, Poland;
| | - Marek Durlik
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of the Ministry of Interior Affairs and Administration, Wołoska St. 137, 02-507 Warsaw, Poland;
| | - Karolina Kędzierska-Kapuza
- Department of Gastroenterological Surgery and Transplantology, Centre of Postgraduate Medical Education, Marymoncka St. 99/103, 01-813 Warsaw, Poland
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