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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; 37:e15008. [PMID: 39873950 PMCID: PMC11996606 DOI: 10.1111/nmo.15008] [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: 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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Yang Y, Zhao B, Wang Y, Lan H, Liu X, Hu Y, Cao P. Diabetic neuropathy: cutting-edge research and future directions. Signal Transduct Target Ther 2025; 10:132. [PMID: 40274830 PMCID: PMC12022100 DOI: 10.1038/s41392-025-02175-1] [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: 08/19/2024] [Revised: 12/12/2024] [Accepted: 02/08/2025] [Indexed: 04/26/2025] Open
Abstract
Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes mellitus, significantly impacting patient quality of life and contributing to morbidity and mortality. Affecting approximately 50% of patients with diabetes, DN is predominantly characterized by distal symmetric polyneuropathy, leading to sensory loss, pain, and motor dysfunction, often resulting in diabetic foot ulcers and lower-limb amputations. The pathogenesis of DN is multifaceted, involving hyperglycemia, dyslipidemia, oxidative stress, mitochondrial dysfunction, and inflammation, which collectively damage peripheral nerves. Despite extensive research, disease-modifying treatments remain elusive, with current management primarily focusing on symptom control. This review explores the complex mechanisms underlying DN and highlights recent advances in diagnostic and therapeutic strategies. Emerging insights into the molecular and cellular pathways have unveiled potential targets for intervention, including neuroprotective agents, gene and stem cell therapies, and innovative pharmacological approaches. Additionally, novel diagnostic tools, such as corneal confocal microscopy and biomarker-based tests, have improved early detection and intervention. Lifestyle modifications and multidisciplinary care strategies can enhance patient outcomes. While significant progress has been made, further research is required to develop therapies that can effectively halt or reverse disease progression, ultimately improving the lives of individuals with DN. This review provides a comprehensive overview of current understanding and future directions in DN research and management.
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Affiliation(s)
- Yang Yang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China.
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
| | - Bing Zhao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuanzhe Wang
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongli Lan
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinyu Liu
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yue Hu
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Peng Cao
- State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China.
- Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
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Dao GM, Kowalski GM, Bruce CR, O'Neal DN, Smart CE, Zaharieva DP, Hennessy DT, Zhao S, Morrison DJ. The Glycemic Impact of Protein Ingestion in People With Type 1 Diabetes. Diabetes Care 2025; 48:509-518. [PMID: 39951019 DOI: 10.2337/dci24-0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/07/2025] [Indexed: 03/23/2025]
Abstract
In individuals with type 1 diabetes, carbohydrate is commonly recognized as the primary macronutrient influencing postprandial glucose levels. Accumulating evidence indicates that protein ingestion also contributes to the increment in postprandial glucose levels, despite endocrine and metabolic responses different from those with carbohydrate ingestion. However, findings regarding protein ingestion's glycemic effect in people with type 1 diabetes are equivocal, with the magnitude of glycemic response seemingly dependent on the rate of absorption and composition of protein ingested. Therefore, the aim of this article is to outline the physiological mechanisms by which ingested protein influences blood glucose regulation in individuals with type 1 diabetes and provide clinical implications on use of dietary protein in the context of glycemic management. Specifically, protein ingestion raises plasma amino acid levels, which directly or indirectly (via gut hormones) stimulates glucagon secretion. Together with the increase in gluconeogenic precursors and an absent endogenous insulin response in individuals with type 1 diabetes, this provides a synergistic physiological environment for increased endogenous glucose production and subsequently increasing circulating glucose levels for several hours. While there is a dearth of well-controlled studies in this area, we provide clinical implications and directions for future research regarding the potential for using ingestion of fast-absorbing protein (such as whey protein) as a tool to prevent and mitigate overnight- and exercise-induced hypoglycemia in people with type 1 diabetes.
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Affiliation(s)
- Giang M Dao
- Institute for Physical Activity and Nutrition, School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Greg M Kowalski
- Institute for Physical Activity and Nutrition, School of Medicine, Deakin University, Geelong, Victoria, Australia
| | - Clinton R Bruce
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
| | - David N O'Neal
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Carmel E Smart
- Department of Pediatrics Diabetes and Endocrinology, John Hunter Children's Hospital, Newcastle, New South Wales, Australia
| | - Dessi P Zaharieva
- Division of Pediatric Endocrinology, Department of Pediatrics, Stanford University, Stanford, CA
| | - Declan T Hennessy
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Sam Zhao
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Dale J Morrison
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
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Phan J, Chang P, Issa D, Turner R, Dodge J, Westanmo A, Karna R, Olive L, Bahdi F, Aldzhyan V, Bilal M, Tielleman T. Glucagon-Like Peptide Receptor Agonists Use Before Endoscopy Is Associated With Low Retained Gastric Contents: A Multicenter Cross-Sectional Analysis. Am J Gastroenterol 2025; 120:554-561. [PMID: 39016372 DOI: 10.14309/ajg.0000000000002969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 07/11/2024] [Indexed: 07/18/2024]
Abstract
INTRODUCTION While ubiquity of glucagon-like peptide receptor agonists (GLP1-RAs) is rising, guidance from the gastroenterology societies and American Society of Anesthesiologist (ASA) remains in conflict on recommendations regarding preoperative holding before endoscopy. The aim of this study was to address this by evaluating the effect of GLP1-RAs on gastric retention during upper endoscopy. METHODS This multicenter cross-sectional study included patients on confirmed GLP1-RAs receiving an endoscopy from 2021 to 2023. Demographics, prescribing practices, and procedure outcomes were captured. GLP1-RA management of preoperative holding was retroactively classified per ASA guidance. Multivariable logistic regression was performed to assess factors influencing retained gastric contents. RESULTS Of 815 patients, 70 (8.7%) had retained gastric contents on endoscopy of whom 65 (93%) had type 2 diabetes mellitus. Only 1 (1.4%) of these patients required unplanned intubation, and none had aspiration events. Those with GLP1-RA held per ASA guidance (406, 49.8%) were less likely to have retained contents (4.4% vs 12.7%, P < 0.001), but there were no significant differences to intubation (0% vs 2%, P = 0.53) or aborting procedure rates (28% vs 18%, P = 0.40) due to gastric retention. On multivariable analysis, likelihood of food retention increased 36% (95% confidence interval 1.15-1.60) for every 1% increase in hemoglobin A1C after adjusting for GLP1-RA type and preoperative medication hold. DISCUSSION In this multicenter study, very low rates of retained gastric contents were seen during endoscopy in patients on GLP1-RAs and most were in patients with type 2 diabetes mellitus. Our findings suggest an individualized approach rather than universal preoperative holding of medications before endoscopy.
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Affiliation(s)
| | | | - Danny Issa
- University of California Los Angeles, Los Angeles, California, USA
| | - Ronald Turner
- The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | | | | | - Rahul Karna
- Minneapolis VA Medical Center, Minneapolis, Minnesota, USA
| | - Lorenzo Olive
- The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Firas Bahdi
- University of California Los Angeles, Los Angeles, California, USA
| | - Vahagn Aldzhyan
- University of California Los Angeles, Los Angeles, California, USA
| | - Mohammad Bilal
- Minneapolis VA Medical Center, Minneapolis, Minnesota, USA
| | - Thomas Tielleman
- The University of Texas Southwestern Medical Center, Dallas, Texas, USA
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Rocha GR, de Melo FF. Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes. World J Diabetes 2025; 16:99928. [PMID: 39959274 PMCID: PMC11718485 DOI: 10.4239/wjd.v16.i2.99928] [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: 08/04/2024] [Revised: 10/25/2024] [Accepted: 11/04/2024] [Indexed: 12/30/2024] Open
Abstract
This letter comments on a study by Jin et al, published recently in the World Journal of Diabetes. Hypoglycemia is a significant complication of diabetes, with primary defense mechanisms involving the stimulation of glucagon secretion in α-cells and the inhibition of insulin secretion in pancreatic β-cells, which are often compromised in type 1 diabetes mellitus (T1DM) and advanced type 2 diabetes mellitus. Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness, a condition underpinned by complex pathophysiological processes, encompassing central nervous system adaptations and several hormonal interactions, including a potential role for glucagon-like peptide-1 (GLP-1) in paracrine and endocrine vias. Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreatic δ-cells, which inhibits glucagon secretion from neighboring α-cells. However, current trials evaluating GLP-1 receptor agonists (GLP-1 RAs) in T1DM patients have shown promising benefits in reducing insulin requirements and body weight, without increasing the risk of hypoglycemia. Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex, and their impact on hypoglycemia unawareness in T1DM patients.
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Affiliation(s)
- Gabriel Reis Rocha
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45065-430, Bahia, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45065-430, Bahia, Brazil
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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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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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Yang DY, Camilleri M. The goals for successful development of treatment in gastroparesis. Neurogastroenterol Motil 2024; 36:e14849. [PMID: 38884392 DOI: 10.1111/nmo.14849] [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: 02/29/2024] [Revised: 04/10/2024] [Accepted: 06/05/2024] [Indexed: 06/18/2024]
Abstract
BACKGROUND Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades. PURPOSE The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.
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Affiliation(s)
- David Yi Yang
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Alshaikh AA, Alshehri AAA, Alshehri AZA, Alobaid AS, Mohammed AA, Saeed F Alshahrani T, Albarqi AZM, Sultan HSH, Alhussen M, Shehri ADA, Ghazy RM. Prevalence of gastrointestinal manifestations among diabetic patients in the Aseer region: A cross-sectional study. Medicine (Baltimore) 2024; 103:e39895. [PMID: 39331911 PMCID: PMC11441854 DOI: 10.1097/md.0000000000039895] [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: 08/10/2024] [Accepted: 09/11/2024] [Indexed: 09/29/2024] Open
Abstract
Diabetes mellitus (DM) has a systemic consequence, influencing many systems of the body, including metabolic functions. This study aimed to determine the prevalence of gastrointestinal complications among patients with type 2 DM in the Asser region of Saudi Arabia, identify sources of information, and investigate the association of these symptoms with disease duration and glycated hemoglobin. This cross-sectional study was conducted between November 13 and December 27, 2023. The questionnaire collected demographic data including age, sex, education, employment, income, and nationality, and 16 questions (5 points for each symptom) about the frequency of gastrointestinal symptoms in the past 3 months. The total score was 80, participants were categorized based on their total scores into 2 groups: those scoring 40 or below, and those scoring above 40. A total of 230 patients were included in this study, their median age was 32.0 (24.00) years, 60% were men, 63.9% were married, 38.7% earned between 5000 and 10,000 Saudi Riyal/month, 85.2% did not work in the medical field, 39.1% held university degrees, 54.8% did not have health insurance, 70.4% did not smoke, 35.7% worked in government jobs, 63% lived in urban areas, 95.2% were Saudi and 53.5% had only DM. More than half of the respondents, 57.4%, relied on doctors for information about DM. Dysmotility symptoms were common: dyspepsia affected 26.5% often and 5.7% always; early satiety impacted 24.3% often and 5.2% always; and bloating affected 28.3% often and 10.9% always. Constipation/diarrhea were a common complaint, with 23.5% of patients experiencing them often and an additional 4.8% reporting it always. Stool consistency also varied widely, with 21.7% experiencing lumpy or hardened stool. Health insurance status and having chronic diseases showed significant association with the severity of symptoms. Duration of diabetes and glycated hemoglobin were associated with the frequency of the symptoms. Gastrointestinal symptoms are common among diabetic patients in Aseer. The frequency of symptoms is associated with glycemic control, duration of diabetes, and health insurance status. These findings highlight the need for improved management and support for better gastrointestinal health in diabetes.
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Affiliation(s)
- Ayoub Ali Alshaikh
- Family & Community Medicine Department, College of Medicine, King Khalid University, Abha, Saudia Arabia
| | | | | | | | | | | | | | | | - Mohammed Alhussen
- Medical Colleague, College of Medicine, King Khalid University, Abha, Saudia Arabia
| | | | - Ramy Mohamed Ghazy
- Family & Community Medicine Department, College of Medicine, King Khalid University, Abha, Saudia Arabia
- Tropical Health Department, High Institute of Public Health, Alexandria University, Alexandria, Egypt
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10
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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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11
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Lin D, Wang H, Ou Y, Li L, Zhang Q, Yan J, Peng D, Peng S. The role of diet in diabetes gastroparesis treatment: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2024; 15:1379398. [PMID: 38957444 PMCID: PMC11217167 DOI: 10.3389/fendo.2024.1379398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 06/04/2024] [Indexed: 07/04/2024] Open
Abstract
Background Diabetic gastroparesis is a common complication in patient with diabetes. Dietary intervention has been widely used in the treatment of diabetic gastroparesis. The aim of this study is to evaluate the role of diet in the treatment of diabetic gastroparesis. Methods This systematic review was conducted a comprehensive search of randomized controlled trials using dietary interventions for the treatment of diabetic gastroparesis up to 9 November 2023. The primary outcomes were gastric emptying time and clinical effect, while fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin were secondary outcomes. Data analysis was performed using RevMan 5.4 software, and publication bias test was performed using Stata 15.1 software. Results A total of 15 randomized controlled trials involving 1106 participants were included in this review. The results showed that patients with diabetic gastroparesis benefit from dietary interventions (whether personalized dietary care alone or personalized dietary care+routine dietary care). Compared with routine dietary care, personalized dietary care and personalized dietary care+routine dietary care can shorten the gastric emptying time, improve clinical efficacy, and reduce the level of fasting blood glucose, 2-hour postprandial blood glucose and glycosylated hemoglobin. Conclusions Limited evidence suggests that dietary intervention can promote gastric emptying and stabilize blood glucose control in patients with diabetic gastroparesis. Dietary intervention has unique potential in the treatment of diabetic gastroparesis, and more high-quality randomized controlled trials are needed to further validate our research results. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD42023481621.
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Affiliation(s)
- Dezhi Lin
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hui Wang
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yangxu Ou
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Longlong Li
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiang Zhang
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jiayin Yan
- Department of Rehabilitation, Zhongjiang County Hospital of Traditional Chinese Medicine, Deyang, China
| | - Dezhong Peng
- School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Sihan Peng
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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12
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Liu J, Zhang F, Cheng L, Zheng H, Ma R, Wang X, Fang S, Liu Y. Is Intravenous Dextrose Infusion During Emergence From Anesthesia Effective in Improving the PONV in Gynecologic Laparoscopy? A Randomized Controlled Trial. J Minim Invasive Gynecol 2024; 31:285-294. [PMID: 38237658 DOI: 10.1016/j.jmig.2024.01.006] [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: 09/28/2023] [Revised: 12/27/2023] [Accepted: 01/10/2024] [Indexed: 02/12/2024]
Abstract
STUDY OBJECTIVE This study aimed to explore the relationship between intravenous 5% dextrose infusion during emergence from anesthesia to postoperative nausea and vomiting (PONV) in patients after gynecologic laparoscopic surgery. DESIGN This was a double-blind randomized controlled trial. Participants were randomized into the experimental group and control group using a computer-generated random number generator. Intervenors and measurers were blinded to group assignments of the study. SETTING A single academic tertiary medical center. PATIENTS Patients undergoing gynecologic laparoscopic surgery. INTERVENTIONS On completion of surgery, participants were randomized into the test group (receive 5% dextrose) and control group (receive Ringer's lactate solution). MEASUREMENTS AND MAIN RESULTS The primary outcome of the present study was the incidence of PONV. Other outcomes included postoperative rescue analgesic and rescue antiemetic, postoperative pain response, and recovery time of postanesthesia care unit. Baseline characteristics were statistically similar between the 2 groups of participants. There were 49 of 105 patients experienced PONV within 24 hours postoperatively. The overall incidence of PONV within 24 hours postoperatively was not significantly different (45.5% vs 48%; relative risk [RR], 0.95; 95% confidence interval [CI], 0.67-1.37; p = .794). However, fewer patients experienced PONV in the test group than in the control group during 0 to 1 hours (6.0% vs 20.0%; RR, 0.85; 95% CI, 0.73-0.99; p = .024) and 1 to 3 hours (14.5% vs 32.0%; RR, 0.80; 95% CI, 0.64-0.99; p = .033) postoperatively. In addition, recovery time in the postanesthesia care unit was less in the test group (17.07 ± 6.36 vs 22.04 ± 7.33; mean difference, -4.97; 95% CI, -7.62 to -2.32; p <.001) and pain score was lower in the test group during 0 to 0.5 hours postoperatively (2.29 ± 1.74 vs 3.08 ± 1.64; mean difference, -0.79; 95% CI, -1.45 to -0.13; p = .019). CONCLUSION In patients after gynecologic laparoscopic surgery, postanesthesia 5% dextrose infusion may be useful in improving the early management of PONV and pain response and may warrant further study.
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Affiliation(s)
- Jiang Liu
- School of Nursing, Shandong Second Medical University (J. Liu, Cheng, and Dr. Y. Liu), Weifang, China
| | - Fengxian Zhang
- Department of Cardiology, Zibo Central Hospital (Zhang), Zibo, China
| | - Lin Cheng
- School of Nursing, Shandong Second Medical University (J. Liu, Cheng, and Dr. Y. Liu), Weifang, China
| | - Hongwei Zheng
- Department of Anesthesiology, Weifang People's Hospital (Drs. Zheng, Ma, Wang, and Fang), Weifang, China
| | - Rong Ma
- Department of Anesthesiology, Weifang People's Hospital (Drs. Zheng, Ma, Wang, and Fang), Weifang, China
| | - Xiaoyan Wang
- Department of Anesthesiology, Weifang People's Hospital (Drs. Zheng, Ma, Wang, and Fang), Weifang, China
| | - Shirong Fang
- Department of Anesthesiology, Weifang People's Hospital (Drs. Zheng, Ma, Wang, and Fang), Weifang, China
| | - Yuxiu Liu
- School of Nursing, Shandong Second Medical University (J. Liu, Cheng, and Dr. Y. Liu), Weifang, China.
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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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14
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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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15
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Lee J, Park HL, Park SY, Lim CH, Kim MH, Lee JM, Chang SA, Oh JH. Gastroparesis might not be uncommon in patients with diabetes mellitus in a real-world clinical setting: a cohort study. BMC Gastroenterol 2024; 24:30. [PMID: 38212710 PMCID: PMC10782575 DOI: 10.1186/s12876-023-03106-6] [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: 10/26/2023] [Accepted: 12/25/2023] [Indexed: 01/13/2024] Open
Abstract
BACKGROUND This study investigated the frequency of diabetic gastroparesis and associated risk factors in a real-world clinical setting. METHODS This retrospective cross-sectional study included patients who underwent assessments of solid gastric emptying time (GET) by technetium-99 m scintigraphy between May 2019 and December 2020. We categorized patients into three groups according to gastric retention of technetium-99 m: rapid (< 65% at 1 h or < 20% at 2 h), normal (≤60% at 2 h and/or ≤ 10% at 4 h), and delayed (> 60% at 2 h and/or > 10% at 4 h). RESULTS Patients with diabetes mellitus (DM) were more likely to show abnormal GET than those without DM (119 [70.8%] vs. 16 [44.4%]). The mean glycated A1c was 10.3% in DM patients. DM patients with normal GET were significantly younger (57.2 years, P = 0.044) than those with delayed (65.0 years) or rapid GET (60.2 years). Fasting glucose levels were the lowest in the normal GET group and the highest in the rapid GET group (delayed: 176.3 mg/dL, normal: 151.2 mg/dL, rapid: 181.0 mg/dL, P = 0.030). However, glycated A1c was not significantly different among the delayed, normal, and rapid GET groups in patients with DM. Patients with delayed and rapid GET showed a higher frequency of retinopathy (6.0 vs. 15.5%, P = 0.001) and peripheral neuropathy (11.3 vs. 24.4%, P = 0.001) than those with normal GET. In the multinomial logistic regression analysis, retinopathy demonstrated a positive association with delayed GET, while nephropathy showed a significant negative correlation. CONCLUSION DM gastroparesis in the clinical setting was not uncommon. Abnormal GET, including delayed and rapid GET, was associated with DM retinopathy or peripheral neuropathy.
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Affiliation(s)
- Jeongmin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Hye Lim Park
- Division of Nuclear medicine, Department of Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Su Young Park
- Division of Nuclear medicine, Department of Radiology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Chul-Hyun Lim
- Division of Gastroenterology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea
| | - Min-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Jung Min Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Sang-Ah Chang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 03312, South Korea
| | - Jung-Hwan Oh
- Division of Gastroenterology, Department of Internal Medicine, The Catholic University of Korea, Seoul, 03312, Republic of Korea.
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Zahid SA, Tated R, Mathew M, Rajkumar D, Karnik SB, Pramod Roy A, Jacob FP, Baskara Salian R, Razzaq W, Shivakumar D, Khawaja UA. Diabetic Gastroparesis and its Emerging Therapeutic Options: A Narrative Review of the Literature. Cureus 2023; 15:e44870. [PMID: 37814758 PMCID: PMC10560130 DOI: 10.7759/cureus.44870] [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: 07/15/2023] [Accepted: 09/06/2023] [Indexed: 10/11/2023] Open
Abstract
Diabetic gastroparesis (DG) is one of the many complications of diabetes mellitus (DM). Even though this condition surfaces years after uncontrolled disease, it affects the quality of life in several ways and causes significant morbidity. Common symptoms experienced by the patients include postprandial nausea, vomiting, abdominal fullness, and pain. Strict glycemic control is essential to evade the effects of DG. The purpose of this review article is to briefly study the pathophysiology, clinical features, diagnostic modalities, and the effects of DG on different aspects of life. Furthermore, it also focuses on the emerging treatment modalities for DG. Tradipitant and relamorelin are two such treatment options that are gaining noteworthy recognition and are discussed in detail in this review article. As observed through various clinical trials, these drugs help alleviate symptoms like nausea, vomiting, abdominal pain, and bloating in patients suffering from DG, thereby targeting the most common and bothersome symptoms of the disease. This leads to an improvement in the quality of life, making it a reliable treatment option for this disease. But while pharmacological intervention is vital, psychological support and lifestyle changes are equally important and are the reason why a multidisciplinary approach is required for the treatment of DG.
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Affiliation(s)
- Shiza A Zahid
- Department of Internal Medicine, Jinnah Sindh Medical University, Karachi, PAK
| | - Ritu Tated
- Department of Internal Medicine, Mahatma Gandhi Mission Institute of Medical Sciences, Navi Mumbai, IND
| | - Midhun Mathew
- Department of Internal Medicine, Pennsylvania Hospital, Philadelphia, USA
| | - Daniel Rajkumar
- Department of Internal Medicine, Hospital Alor Gajah, Alor Gajah, MYS
| | - Siddhant B Karnik
- Department of Internal Medicine, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, IND
| | | | - Fredy P Jacob
- Department of Internal Medicine, Jonelta Foundation School of Medicine, University of Perpetual Help System DALTA, Las Piñas, PHL
| | | | - Waleed Razzaq
- Department of Internal Medicine, Services Hospital Lahore, Lahore, PAK
| | - Divya Shivakumar
- Department of Internal Medicine, Kamineni Academy of Medical Sciences and Research Center, Hyderabad, IND
| | - Uzzam Ahmed Khawaja
- Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK
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Phan F, Halbron M, Jacqueminet S, Popelier M, Soliman H, Coffin B, Hartemann A, Amouyal C. Improved dyspeptic symptoms of type 1 diabetes adults with gastroparesis on hybrid closed loop system: A case series. DIABETES & METABOLISM 2023; 49:101471. [PMID: 37657737 DOI: 10.1016/j.diabet.2023.101471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/15/2023] [Accepted: 08/19/2023] [Indexed: 09/03/2023]
Affiliation(s)
- Franck Phan
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France; Centre de Recherche des Cordeliers, INSERM, UMR_S 1138, Paris, France; Institute of Cardiometabolism and Nutrition ICAN, Paris, France
| | - Marine Halbron
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France; Institute of Cardiometabolism and Nutrition ICAN, Paris, France
| | - Sophie Jacqueminet
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France; Institute of Cardiometabolism and Nutrition ICAN, Paris, France
| | - Marc Popelier
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France; Institute of Cardiometabolism and Nutrition ICAN, Paris, France
| | - Heithem Soliman
- INSERM, UMR 1149, Université de Paris-Cité, équipe PIMS, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), DMU Esprit, Gastroenterology Unit, Louis Mourier Hospital, Colombes, France; Université Paris Cité, Paris, France
| | - Benoit Coffin
- INSERM, UMR 1149, Université de Paris-Cité, équipe PIMS, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), DMU Esprit, Gastroenterology Unit, Louis Mourier Hospital, Colombes, France; Université Paris Cité, Paris, France
| | - Agnès Hartemann
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France; Centre de Recherche des Cordeliers, INSERM, UMR_S 1138, Paris, France; Institute of Cardiometabolism and Nutrition ICAN, Paris, France
| | - Chloé Amouyal
- Sorbonne Université, Paris, France; Assistance Publique-Hôpitaux de Paris (APHP), Diabetology Department, La Pitié Salpêtrière-Charles Foix University Hospital, Paris, France; Institute of Cardiometabolism and Nutrition ICAN, Paris, France; Nutrition and Obesities: Systemic Approaches (NutriOmics) Research Unit, INSERM, UMRS U1269, Paris, France.
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Early Gastrointestinal Neuropathy Assessed by Wireless Motility Capsules in Adolescents with Type 1 Diabetes. J Clin Med 2023; 12:jcm12051925. [PMID: 36902712 PMCID: PMC10003990 DOI: 10.3390/jcm12051925] [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: 12/21/2022] [Revised: 02/03/2023] [Accepted: 02/20/2023] [Indexed: 03/06/2023] Open
Abstract
BACKGROUND To assess the prevalence of objective signs of gastrointestinal (GI) autonomic neuropathy (AN) in adolescents with type 1 diabetes (T1D). In addition, to investigate associations between objective GI findings and self-reported symptoms or other findings of AN. METHODS Fifty adolescents with T1D and 20 healthy adolescents were examined with a wireless motility capsule to assess the total and regional GI transit times and motility index. GI symptoms were evaluated with the GI Symptom Rating Scale questionnaire. AN was evaluated with cardiovascular and quantitative sudomotor axon reflex tests. RESULTS There was no difference in GI transit times in adolescents with T1D and healthy controls. Adolescents with T1D had a higher colonic motility index and peak pressure than the controls, and GI symptoms were associated with low gastric and colonic motility index (all p < 0.05). Abnormal gastric motility was associated with the duration of T1D, while a low colonic motility index was inversely associated with "time in target range" for blood glucose (all p < 0.01). No associations were found between signs of GI neuropathy and other measures of AN. CONCLUSIONS Objective signs of GI neuropathy are common in adolescents with T1D and it seems to require early interventions in patients at high risk of developing GI neuropathy.
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Luo WY, Gao L, Zhao DD, Zhang L, Gao B, Lei G, Dong GT, Wei JP. Yunvjian Improves Glucose and Insulin Function in Diabetic Rats by Regulating Gastric Emptying Function. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:8551406. [PMID: 36691597 PMCID: PMC9867596 DOI: 10.1155/2023/8551406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Revised: 11/17/2022] [Accepted: 12/05/2022] [Indexed: 01/15/2023]
Abstract
BACKGROUND Diet acts on the human body through digestion in the stomach and absorption in the intestines. Thus, the emptying of the stomach should be the focus of the research mechanism of the combined medicine and food treatment of diabetes. The emptying function of the stomach and the secretion of related hormones may be the key points of traditional Chinese medicine. In the clinic, Yunvjian is a famous traditional Chinese formula for preventing and curing diabetes. However, the pharmacological action and mechanism of Yunvjian are also need to be probe. OBJECTIVE To assess the effect of Yunvjian on glucose, insulin level and gastric emptying function and related hormones on high-fat diet combined with STZ-induced diabetic rats. METHODS High-fat diet combined with STZ was used to construct type 2 diabetes mellitus (T2DM) rats model and received a 4-week Yunvjian administration. The animals were divided into 6 groups, respectively, as the Control group, the DM group, the DM + Acarbose group, the DM + YNH group, and the DM + YNL group. Radionuclide single-photon emission computed tomography (SPECT) technology was used to observe the gastric emptying rate and half-empty time; blood was took to test fasting insulin, and then the insulin resistance index (HOMA-IR) was calculated; HE staining was performed to detect islets and gastric antrum, immunohistochemical staining was performed to detect the number and morphology of pancreatic β cells and gastric antrum Cajal cells, and the average optical density was calculated; the expression of ghrelin hormone in gastric antrum and serum was detected by ELISA and immunofluorescence; the expression of GHRS mRNA in gastric antrum was detected by RT-PCR method. RESULTS Yunvjian could significantly improve the glucose level and insulin function of rats. Compared with the DM group, Yunvjian was beneficial to low fasting blood glucose (FBG) (P < 0.01), increased glucose tolerance, and improved islet function at the same time (P < 0.05). At the same time, compared with the DM group (25.02 ± 0.05, 44 ± 12.33), the emptying rate of the DM + YNH group was significantly faster (64.98 ± 0.12), and the half row time was shortened (26 ± 8.29, P < 0.05). The gastric ghrelin levels in each group of Yunvjian increased with different degrees compared with the DM group (616.2 ± 26.23), especially in the DM + YNH group (863.51 ± 23.76, P < 0.01). Correspondingly, the expression of gastric GHSR mRNA in the DM + YNH and DM + YNL groups increased significantly compared with the DM group (P < 0.01). CONCLUSIONS Yunvjian can effectively control glucose and improve islet function, which may be closely related to its influence on gastric emptying function and related hormone secretion regulation.
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Affiliation(s)
- Wan-Yu Luo
- Department of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- Department of Traditional Chinese Medicine, Shandong Traditional Chinese Medicine University, Shandong, Jinan, China
| | - Lin Gao
- Department of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Dan-Dan Zhao
- Department of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Lin Zhang
- Department of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Bo Gao
- Department of Nuclear Medicine, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Guang Lei
- Department of Nuclear Medicine, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Guang-Tong Dong
- Department of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jun-Ping Wei
- Department of Endocrinology, Guang' anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
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20
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Betônico CC, Cobello AV, Santos-Bezerra DP, de A. Leite AZ, Correa-Giannella ML, Nery M, Queiroz MS. Diet consistency modification improves postprandial glycemic and gastroparesis symptoms. J Diabetes Metab Disord 2022; 21:1661-1667. [PMID: 36404814 PMCID: PMC9672186 DOI: 10.1007/s40200-022-01117-w] [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: 03/25/2022] [Accepted: 08/23/2022] [Indexed: 12/01/2022]
Abstract
Abstract Diabetic gastroparesis (DGP) is an autonomic neuropathy resulting from long-standing poorly controlled diabetes, and it is also linked to fluctuations in glycemic control due to variability on nutrient absorption. Objectives Considering the scarcity of information, the aim of this study was to identify the impact of modifications on diet consistency on post-prandial glucose variability using a continuous glucose monitoring (CGM) and its effect on the perception and severity of gastrointestinal symptoms. Methods This proof-of-concept study was carried out in a cross-sectional cohort of six individuals with type 1 diabetes mellitus with confirmed diagnosis of DGP. Two types of diet were used to evaluate glycemic control and DGP symptoms, general consistency standard meal (SD) and modified consistency test diet (MD), associated with an application of rapid acting insulin at the time of food intake. Glycemic control was evaluated by CGM, and the Gastroparesis Cardinal Symptom Index (GCSI) was applied after meals. Results The CGM curve was different for MD + insulin and SD + insulin. There was a smaller increment of interstitial glucose with 2 h after MD + insulin, returning almost to the basal level 4 h later. Patients scored significantly lower GCSI after MD + insulin compared to the same index after they received SD + insulin. Moreover, there was a decrease in important clinical scores present in the index, like: "Not able to finish meal", "Loss of appetite" and "Stomach or belly feels larger". Conclusion This study showed that a modified diet can improve postprandial glycemic excursion and the perception and severity of gastroparesis symptoms. Supplementary Information The online version contains supplementary material available at 10.1007/s40200-022-01117-w.
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Affiliation(s)
- Carolina C. Betônico
- School of Medicine, UNIFAI–Faculdades Adamantinenses Integradas, Adamantina, São Paulo, Brazil
| | - Aline Vial Cobello
- Nutrition and Dietetics Division, Central Institute of Clinics Hospital, University of São Paulo Medical School, São Paulo, Brazil
| | - Daniele P. Santos-Bezerra
- Laboratory of Carbohydrates and Radioimmunoassays (LIM-18), Discipline of Endocrinology and Metabolism, Faculdade de Medicina, Universidade São Paulo, São Paulo, Brazil
- School of Medicine, São Paulo, SP Brazil
| | - André Z. de A. Leite
- Laboratory of Medical Investigation (LIM-07), Universidade de Sao Paulo Hospital das Clínicas Sao Paulo, São Paulo, Brazil
| | - Maria Lúcia Correa-Giannella
- Laboratory of Carbohydrates and Radioimmunoassays (LIM-18), Discipline of Endocrinology and Metabolism, Faculdade de Medicina, Universidade São Paulo, São Paulo, Brazil
- School of Medicine, São Paulo, SP Brazil
| | - Márcia Nery
- Endocrinology Division, Internal Medicine Department, Hospital das Clinicas Faculdade de Medicina, Universidade São Paulo, São Paulo, Brazil
| | - Márcia S. Queiroz
- Department of Graduation in Medicine, Universidade Nove de Julho (UNINOVE), Rua Vergueiro, 235/249 - Liberdade, São Paulo, SP 01525-000 Brazil
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21
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Yan C, Dai C, Liu N, Qian W, Yang P, Hou X. Effects of Simo decoction on gastric motility of diabetic rats. Neurogastroenterol Motil 2022; 34:e14450. [PMID: 36111645 DOI: 10.1111/nmo.14450] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 06/27/2022] [Accepted: 07/27/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND To investigate the effects of simo decoction (SMD) on the gastric motility of diabetic rats. METHODS Diabetic rats were gavaged with various doses of SMD (0.15, 1.5, and 3.0 ml/kg/d) or saline, and their blood glucose levels and body weight were monitored. Gastric emptying and antral motility were assessed by phenol red retention and contractions of antral strips, respectively. The levels of substance P (SP), vasoactive intestinal peptide (VIP), and neurogenic nitric oxide synthase (nNOS) in the gastric antrum were determined by real-time polymerase chain reaction and Western blot. RESULTS Gastric emptying was delayed in diabetic rats (p < 0.01 vs. non-diabetic controls) but accelerated after SMD administration (p < 0.01). The contractions of antral strips were reduced in diabetic rats (p < 0.01 vs. non-diabetic controls) but improved after SMD intervention (p < 0.05). The mRNA expressions of SP, VIP, and nNOS in diabetic rats were downregulated compared with non-diabetic controls (all p < 0.01). Simo decoction treatment did not affect the expression of these factors in diabetic rats. The protein levels of SP, VIP, and nNOS in diabetic rats were decreased (p < 0.01), increased (p < 0.01), and comparable (p > 0.05), respectively, in comparison with non-diabetic controls. Simo decoction administration increased SP protein expression (p < 0.01) and decreased the levels of VIP (p < 0.01) and nNOS (p < 0.01) in diabetic rats. CONCLUSIONS Simo decoction improved gastric dysmotility of diabetic rats possibly by upregulating SP and downregulating VIP and nNOS.
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Affiliation(s)
- Caihua Yan
- Department of Gastroenterology, Renhe Hospital Affiliated to China Three Gorges University, Yichang, China
| | - Chibing Dai
- Department of Gastroenterology, Renhe Hospital Affiliated to China Three Gorges University, Yichang, China
| | - Na Liu
- Department of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Qian
- Department of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Pengchun Yang
- Department of Gastroenterology, Renhe Hospital Affiliated to China Three Gorges University, Yichang, China
| | - Xiaohua Hou
- Department of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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22
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Gastroparesis in pregnancy. Am J Obstet Gynecol 2022; 228:382-394. [PMID: 36088986 DOI: 10.1016/j.ajog.2022.09.002] [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: 04/23/2022] [Revised: 08/21/2022] [Accepted: 09/05/2022] [Indexed: 01/30/2023]
Abstract
Gastroparesis is a functional gastrointestinal disorder that more commonly affects women, with most cases being diagnosed during childbearing age. However, there is a paucity of data and guidelines to specifically highlight the epidemiology, disease course, maternal and fetal impact, and the management of existing gastroparesis during pregnancy. Apart from metoclopramide, there is no approved therapy specifically indicated for gastroparesis. More importantly, pregnant and breastfeeding women are excluded from clinical trials evaluating pharmacologic agents in the management of gastroparesis. This poses a real challenge to healthcare providers in counseling and managing patients with gastroparesis. In this systematic review, we summarize the current available literature and the knowledge gaps in the impact of pregnancy on gastroparesis and vice versa. We also highlight the efficacy and safety profiles of available pharmacologic and nonpharmacologic therapies in the management of patients with gastroparesis, with emphasis on judicious use of dietary approaches that are deemed relatively safe during pregnancy.
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23
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Tseng PH, Chao CC, Cheng YY, Chen CC, Yang PH, Yang WK, Wu SW, Wu YW, Cheng MF, Yang WS, Wu MS, Hsieh ST. Diabetic visceral neuropathy of gastroparesis: Gastric mucosal innervation and clinical significance. Eur J Neurol 2022; 29:2097-2108. [PMID: 35322505 DOI: 10.1111/ene.15333] [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: 02/27/2022] [Accepted: 03/21/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND PURPOSE The pathogenesis of diabetic gastroparesis due to visceral neuropathy involves multidimensional mechanisms with limited exploration of gastric mucosal innervation. This study aimed to examine quantitatively this topic and its relationship with gastroparesis symptoms and gastric emptying in diabetes. METHODS We prospectively enrolled 22 patients with type 2 diabetes and gastroparesis symptoms and 25 age- and gender-matched healthy controls for comparison. The assessments included: (i) neuropathology with quantification of gastric mucosal innervation density (MID) on endoscopic biopsy; (ii) clinical manifestations based on the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire; and (iii) functional tests of gastric emptying scintigraphy (GES). RESULTS In patients with diabetes, stomach fullness, bloating and feeling excessively full after meals constituted the most common GCSI symptoms. Seven patients with diabetes (32%) had prolonged gastric emptying patterns. In diabetes, gastric MID was significantly lower in all the regions examined compared with the controls: antrum (294.8 ± 237.0 vs. 644.0 ± 222.0 mm/mm3 ; p < 0.001), body (292.2 ± 239.0 vs. 652.6 ± 260.9 mm/mm3 ; p < 0.001), and fundus (238.0 ± 109.1 vs. 657.2 ± 332.8 mm/mm3 ; p < 0.001). Gastric MID was negatively correlated with gastroparesis symptoms and total scores on the GCSI (p < 0.001). Furthermore, gastric MID in the fundus was negatively correlated with fasting glucose and glycated hemoglobin levels. Gastric emptying variables, including half emptying time and gastric retention, were prolonged in patients with diabetes, and gastric retention at 3 h was correlated with fasting glucose level. CONCLUSION In diabetes, gastric MID was reduced and GES parameters were prolonged. Both were correlated with gastroparesis symptoms and glycemic control. These findings provide pathology and functional biomarkers for diabetic visceral neuropathy of gastroparesis and underlying pathophysiology.
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Affiliation(s)
- Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Chao Chao
- Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ya-Yin Cheng
- Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chieh-Chang Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ping-Hao Yang
- School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wei-Kang Yang
- Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shao-Wei Wu
- Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Wen Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Nuclear Medicine and Cardiology of Cardiovascular Medical Centre, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Mei-Fang Cheng
- Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Shiung Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Sung-Tsang Hsieh
- Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
- Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan
- Center of Precision Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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24
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Lin XQ, Chen YR, Chen X, Cai YP, Lin JX, Xu DM, Zheng XC. Impact of preoperative carbohydrate loading on gastric volume in patients with type 2 diabetes. World J Clin Cases 2022; 10:6082-6090. [PMID: 35949825 PMCID: PMC9254193 DOI: 10.12998/wjcc.v10.i18.6082] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/21/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Enhanced recovery after surgery advocates that consuming carbohydrates two hours before anesthesia is beneficial to the patient's recovery. Patients with diabetes are prone to delayed gastric emptying. Different guidelines for preoperative carbohydrate consumption in patients with diabetes remain controversial due to concerns about the risk of regurgitation, aspiration and hyperglycemia. Ultrasonic gastric volume (GV) assessment and blood glucose monitoring can comprehensively evaluate the safety and feasibility of preoperative carbohydrate intake in type 2 diabetes (T2D) patients.
AIM To evaluate the impact of preoperative carbohydrate loading on GV before anesthesia induction in T2D patients.
METHODS Patients with T2D receiving surgery under general anesthesia from December 2019 to December 2020 were included. A total of 78 patients were randomly allocated to 4 groups receiving 0, 100, 200, or 300 mL of carbohydrate loading 2 h before anesthesia induction. Gastric volume per unit weight (GV/W), Perlas grade, changes in blood glucose level, and risk of reflux and aspiration were evaluated before anesthesia induction.
RESULTS No significant difference was found in GV/W among the groups before anesthesia induction (P > 0.05). The number of patients with Perlas grade II and GV/W > 1.5 mL/kg did not differ among the groups (P > 0.05). Blood glucose level increased by > 2 mmol/L in patients receiving 300 mL carbohydrate drink, which was significantly higher than that in groups 1 and 2 (P < 0.05).
CONCLUSION Preoperative carbohydrate loading < 300 mL 2 h before induction of anesthesia in patients with T2D did not affect GV or increase the risk of reflux and aspiration. Blood glucose levels did not change significantly with preoperative carbohydrate loading of < 200 mL. However, 300 mL carbohydrate loading may increase blood glucose levels in patients with T2D before induction of anesthesia.
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Affiliation(s)
- Xin-Qiang Lin
- Department of Anesthesiology, Affiliated Hospital of Putian College, Putian Maternity and Child Care Hospital, Putian 351100, Fujian Province, China
| | - Yu-Ren Chen
- Department of Anesthesiology, Affiliated Hospital of Putian College, Putian 351100, Fujian Province, China
| | - Xiao Chen
- Department of Anesthesiology, Affiliated Hospital of Putian College, Putian 351100, Fujian Province, China
| | - Yu-Ping Cai
- Department of Anesthesiology, Affiliated Hospital of Putian College, Putian 351100, Fujian Province, China
| | - Jian-Xin Lin
- Department of Anesthesiology, Affiliated Hospital of Putian College, Putian 351100, Fujian Province, China
| | - De-Ming Xu
- Department of Anesthesiology, Affiliated Hospital of Putian College, Putian 351100, Fujian Province, China
| | - Xiao-Chun Zheng
- Department of Anesthesiology, Shenli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China
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25
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Meling S, Bertoli D, Sangnes DA, Brock C, Drewes A, Ejskjaer N, Dimcevski G, Søfteland E. Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure? Curr Diabetes Rev 2022; 18:e220321192412. [PMID: 34225633 DOI: 10.2174/1573399817666210322154618] [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: 11/16/2020] [Revised: 01/19/2021] [Accepted: 02/13/2021] [Indexed: 11/22/2022]
Abstract
Autonomic neuropathy in patients with diabetes mellitus, and especially complications related to gastrointestinal neuropathy, are often overlooked in the clinic. Diabetic gastroenteropathy affects every segment of the gastrointestinal tract and generates symptoms that may include nausea, early satiety, vomiting, abdominal pain, constipation, and diarrhea. Severe cases can be complicated by weight loss, dehydration, and electrolyte disturbances. The pathophysiology is complex, the diagnostics and treatment options are multidisciplinary, and there is generally a lack of evidence for the treatment options. The aims for this review are first to summarize the pathophysiology and describe possible and expected symptoms and complications.Further, we will try to supply the clinician with a straightforward tool for diagnostics, and then, we shall summarize established treatment options, including diet recommendations, pharmacological and non-pharmacological options. Finally, we will explore the multiple possibilities of novel treatment, looking at medications related to the pathophysiology of neuropathy, other manifestations of autonomic neuropathies, and symptomatic treatment for other gastrointestinal disorders, also including new knowledge of endosurgical and neuromodulatory treatment. The overall goal is to increase awareness and knowledge on this frequent diabetic complication and to provide better tools for diagnosis and treatment. Ultimately, we hope to encourage further research in this field, as there are clear shortcomings in terms of biomarkers, pathophysiology, as well as treatment possibilities. In conclusion, diagnosis and management of diabetic gastroenteropathy are challenging and often require multidisciplinary teams and multimodal therapies. Treatment options are sparse, but new pharmacological, endoscopic, and neuromodulatory techniques have shown promising results in initial studies.
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Affiliation(s)
- Sondre Meling
- Department of Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Davide Bertoli
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Dag A Sangnes
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | - Christina Brock
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Asbjørn Drewes
- Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Steno Diabetes Center North Jutland, Aalborg, Denmark
| | - Niels Ejskjaer
- Steno Diabetes Center North Jutland, Aalborg, Denmark
- Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark
| | - Georg Dimcevski
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Eirik Søfteland
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Daly A, Hartnell S, Boughton CK, Evans M. Hybrid Closed-loop to Manage Gastroparesis in People With Type 1 Diabetes: a Case Series. J Diabetes Sci Technol 2021; 15:1216-1223. [PMID: 34378426 PMCID: PMC8564229 DOI: 10.1177/19322968211035447] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Gastroparesis is associated with unpredictable gastric emptying and can lead to erratic glucose profiles and negative impacts on quality-of-life. Many people with gastroparesis are unable to meet glycemic targets and there is a need for new approaches for this population. Hybrid closed-loop systems improve glucose control and quality-of-life but evidence for their use in people with diabetic gastroparesis is limited. METHODS We present a narrative review of the challenges associated with type 1 diabetes management for people with gastroparesis and present a case series of 7 people with type 1 diabetes and gastroparesis. We compare glycemic control before and during the first 12 months of hybrid closed-loop therapy. Data were analyzed using electronic patient records and glucose management platforms. We also discuss future advancements for closed-loop systems that may benefit this population. RESULTS Five of 7 patients had data available for time in range before and during hybrid closed-loop therapy, and all had an improvement in percentage time in target glucose range, with the overall mean time in range increasing from 26.0% ± 15.7% to 58.4% ± 8.6% during HCL use, (P = .004). There were significant reductions in HbA1c (83 ± 9 mmol/mol to 71 ± 14 mmol/mol) and mean glucose from 13.0 ± 1.7 mmol/L (234 ± 31 mg/dL) to 10.0 ± 0.7 mmol/L (180 ± 13 mg/dL) with use of a hybrid closed-loop system. Importantly, this was achieved without an increase in time in hypoglycemia (P = .50). CONCLUSION Hybrid closed-loop systems may represent a valuable approach to improve glycemic control for people with type 1 diabetes and gastroparesis. Prospective studies are required to confirm these findings.
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Affiliation(s)
- Aideen Daly
- Wellcome Trust-MRC Institute of
Metabolic Science, University of Cambridge, Cambridge, UK
- Aideen Daly, MB BCh, Wellcome Trust-MRC
Institute of Metabolic Science, University of Cambridge, Level 4, Addenbrookes
Hospital, Cambridge, CB2 0QQ, UK.
| | - Sara Hartnell
- Wolfson Diabetes and Endocrine Clinic,
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Charlotte K. Boughton
- Wellcome Trust-MRC Institute of
Metabolic Science, University of Cambridge, Cambridge, UK
- Wolfson Diabetes and Endocrine Clinic,
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Mark Evans
- Wellcome Trust-MRC Institute of
Metabolic Science, University of Cambridge, Cambridge, UK
- Wolfson Diabetes and Endocrine Clinic,
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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27
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Robinson KN, Cassady BA, Hegazi RA, Wischmeyer PE. Preoperative carbohydrate loading in surgical patients with type 2 diabetes: Are concerns supported by data? Clin Nutr ESPEN 2021; 45:1-8. [PMID: 34620304 DOI: 10.1016/j.clnesp.2021.08.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/24/2021] [Accepted: 08/24/2021] [Indexed: 12/17/2022]
Abstract
Currently, there is a lack of consensus on the provision of preoperative carbohydrate loading in patients with type 2 diabetes mellitus (T2DM) due to theoretical concerns including the possibility of delayed gastric emptying, perioperative hyperglycemia, and poor surgical outcomes. This narrative review summarizes the accumulating evidence on preoperative carbohydrate loading in this population and whether these concerns are supported by preliminary evidence. In general, the available research suggests that carbohydrate loading may be implemented in those with T2DM without increased risk for intra- and postoperative hyperglycemia or surgical complications. However, there is strong justification for future research to definitively study this highly debated and timely topic. Ultimately, the inclusion of preoperative carbohydrate loading for surgical patients with DM should be guided by the surgical team's clinical judgment and individualized based on patient needs and characteristics.
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Affiliation(s)
- Katie N Robinson
- Scientific and Medical Affairs, Abbott Nutrition, 2900 Easton Square Place, Columbus, OH, 43219 USA.
| | - Bridget A Cassady
- Scientific and Medical Affairs, Abbott Nutrition, 2900 Easton Square Place, Columbus, OH, 43219 USA.
| | - Refaat A Hegazi
- Scientific and Medical Affairs, Abbott Nutrition, 2900 Easton Square Place, Columbus, OH, 43219 USA.
| | - Paul E Wischmeyer
- Duke University School of Medicine, Department of Anesthesiology and Surgery, Center for Perioperative Organ Protection (CPOP), DUMC, Box 3094 Mail # 41, 2301 Erwin Road, 5692 HAFS, Durham, NC, 27710 USA.
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28
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Malnick SDH, Fisher D, Somin M, Neuman MG. Treating the Metabolic Syndrome by Fecal Transplantation-Current Status. BIOLOGY 2021; 10:447. [PMID: 34065241 PMCID: PMC8161223 DOI: 10.3390/biology10050447] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/22/2021] [Accepted: 05/14/2021] [Indexed: 12/12/2022]
Abstract
The intestinal microbiome (IM) is important for normal gastrointestinal (GI) and other organ systems' functioning. An alteration in the normal IM, dysbiosis, and changes in intestinal motility result in microorganisms' overgrowth and an alteration in intestinal permeability. The gut-brain axis is also of importance in the irritable bowel syndrome (IBS) and associated bowel overgrowth. Secondary to the epidemic of obesity, the metabolic syndrome has become a major health problem. Disturbances in the fecal microbiome are associated with the metabolic syndrome. Metabolic-associated fatty liver disease (MAFLD) is now the current terminology for non-alcoholic fatty liver disease. IM alteration by fecal transplantation is an approved treatment method for recurrent Clostridioides difficile infection. Initially performed by either duodenal infusion or colonoscopy, it is now easily performed by the administration of capsules containing stools. We discuss the intestinal microbiome-its composition, as well as the qualitative changes of microbiome composition leading to inflammation. In addition, we discuss the evidence of the effect of fecal transplantation on the metabolic syndrome and MAFLD, as well as its clinical indications.
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Affiliation(s)
- Stephen D. H. Malnick
- Department of Internal Medicine Cj Kaplan Medical Center, The Hebrew University, Rehovot 76100, Israel; (S.D.H.M.); (D.F.); (M.S.)
| | - David Fisher
- Department of Internal Medicine Cj Kaplan Medical Center, The Hebrew University, Rehovot 76100, Israel; (S.D.H.M.); (D.F.); (M.S.)
| | - Marina Somin
- Department of Internal Medicine Cj Kaplan Medical Center, The Hebrew University, Rehovot 76100, Israel; (S.D.H.M.); (D.F.); (M.S.)
| | - Manuela G. Neuman
- In Vitro Drug Safety and Biotechnology, Banting Institute, University of Toronto, Toronto, ON M5G 0A3, Canada
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Bonetto S, Gruden G, Beccuti G, Ferro A, Saracco GM, Pellicano R. Management of Dyspepsia and Gastroparesis in Patients with Diabetes. A Clinical Point of View in the Year 2021. J Clin Med 2021; 10:1313. [PMID: 33806716 PMCID: PMC8004823 DOI: 10.3390/jcm10061313] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/12/2021] [Accepted: 03/20/2021] [Indexed: 12/12/2022] Open
Abstract
Diabetes mellitus is a widespread disease, and represents an important public health burden worldwide. Together with cardiovascular, renal and neurological complications, many patients with diabetes present with gastrointestinal symptoms, which configure the so-called diabetic enteropathy. In this review, we will focus on upper gastrointestinal symptoms in patients with diabetes, with particular attention to dyspepsia and diabetic gastroparesis (DG). These two clinical entities share similar pathogenetic mechanisms, which include autonomic neuropathy, alterations in enteric nervous system and histological abnormalities, such as interstitial cells of Cajal depletion. Moreover, the differential diagnosis may be challenging because of overlapping clinical features. Delayed gastric emptying should be documented to differentiate between DG and dyspepsia and it can be assessed through radioactive or non-radioactive methods. The clinical management of dyspepsia includes a wide range of different approaches, above all Helicobacter pylori test and treat. As regards DG treatment, a central role is played by dietary modification and glucose control and the first-line pharmacological therapy is represented by the use of prokinetics. A minority of patients with DG refractory to medical treatment may require more invasive therapeutic approaches, including supplemental nutrition, gastric electric stimulation, pyloromyotomy and gastrectomy.
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Affiliation(s)
- Silvia Bonetto
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (G.M.S.); (R.P.)
| | - Gabriella Gruden
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.G.); (G.B.); (A.F.)
| | - Guglielmo Beccuti
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.G.); (G.B.); (A.F.)
| | - Arianna Ferro
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.G.); (G.B.); (A.F.)
| | - Giorgio Maria Saracco
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (G.M.S.); (R.P.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (G.G.); (G.B.); (A.F.)
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Molinette Hospital, 10126 Turin, Italy; (G.M.S.); (R.P.)
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30
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Rangan V, Ukleja A. Gastroparesis in the Hospital Setting. Nutr Clin Pract 2021; 36:50-66. [PMID: 33336872 DOI: 10.1002/ncp.10611] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 11/04/2020] [Indexed: 12/15/2022] Open
Abstract
Gastroparesis (GP) is commonly seen in hospitalized patients. Refractory vomiting and related dehydration, electrolyte abnormalities, and malnutrition are indications for hospital admission. In addition, tube feeding intolerance is a common sign of gastric dysmotility in critically ill patients. The diagnosis and management of GP in the hospital setting can be quite challenging. Diagnostic tests are often deferred because of patient intolerance of the oral meal for standard scintigraphy or severity of the primary disease. The diagnosis of GP is often established on the basis of clinical scenario and risk factors for gastric motor dysfunction. Medical therapy in GP is directed toward controlling nausea and vomiting by prokinetic and antinausea medications and correcting nutrition risks or treating malnutrition with nutrition therapy. Enteral nutrition is the preferred nutrition intervention for patients with GP. Delayed gastric emptying in critically ill patients has a negative impact on the timely delivery of enteral feeding and meeting the energy and protein goals. Measures to improve gastric tolerance or provide feeding beyond the stomach are often needed, since early enteral nutrition has been an important target of therapy for critically ill patients. This review will address the current understanding of the mechanisms of GP and feeding intolerance in critical illness, diagnostic workup, drug therapies, and interventions to improve the provision of enteral nutrition in hospital settings when gastric dysmotility is present or suspected.
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Affiliation(s)
- Vikram Rangan
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Ukleja
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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31
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Singh R, Zogg H, Wei L, Bartlett A, Ghoshal UC, Rajender S, Ro S. Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders. J Neurogastroenterol Motil 2021; 27:19-34. [PMID: 33166939 PMCID: PMC7786094 DOI: 10.5056/jnm20149] [Citation(s) in RCA: 133] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 08/26/2020] [Accepted: 10/03/2020] [Indexed: 12/11/2022] Open
Abstract
Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders.
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Affiliation(s)
- Rajan Singh
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Hannah Zogg
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Lai Wei
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Allison Bartlett
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Singh Rajender
- Department of Endocrinology, Central Drug Research Institute, Lucknow, India
| | - Seungil Ro
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
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Xie C, Huang W, Wang X, Trahair LG, Pham HT, Marathe CS, Young RL, Jones KL, Horowitz M, Rayner CK, Wu T. Gastric emptying in health and type 2 diabetes: An evaluation using a 75 g oral glucose drink. Diabetes Res Clin Pract 2021; 171:108610. [PMID: 33301790 DOI: 10.1016/j.diabres.2020.108610] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 10/14/2020] [Accepted: 12/03/2020] [Indexed: 02/07/2023]
Abstract
AIM Gastric emptying is a major determinant of the glycaemic response to carbohydrate and is frequently abnormal in type 2 diabetes (T2DM). There is little information about how chronic glycaemic control affects gastric emptying in T2DM. We evaluated gastric emptying of a 75 g glucose drink in community-based patients with T2DM of short duration with good or poor glycaemic control, and compared this to young and older controls. METHODS T2DM patients managed by diet and/or metformin, either well-controlled or poorly-controlled, together with young and age-matched older controls without diabetes, consumed a 75 g oral glucose drink containing 150 mg 13C-acetate for evaluation of gastric emptying (breath test) and blood glucose over 180 min. RESULTS The gastric half-emptying time (T50) was longer in the older than the young non-diabetic subjects (P = 0.041), but shorter in well-controlled T2DM patients than age-matched older controls (P = 0.043). The T50 in poorly-controlled T2DM patients was shorter than in older controls (P = 0.006), but similar to young non-diabetic subjects. CONCLUSIONS Gastric emptying of a glucose drink is delayed with ageing, but more rapid in patients with T2DM of relatively short duration, regardless of their glycaemic status. These observations support interventions that slow gastric emptying to improve postprandial glycaemia in these patients with T2DM.
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Affiliation(s)
- Cong Xie
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Weikun Huang
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Xuyi Wang
- Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China
| | - Laurence G Trahair
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Hung T Pham
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia
| | - Chinmay S Marathe
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide, Australia
| | - Richard L Young
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Nutrition, Diabetes & Gut Health, Lifelong Health Theme South Australian Health & Medical Research Institute, Adelaide, Australia
| | - Karen L Jones
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Michael Horowitz
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Christopher K Rayner
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia
| | - Tongzhi Wu
- Adelaide Medical School and Centre of Research Excellence (CRE) in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, Australia; Institute of Diabetes, School of Medicine, Southeast University, Nanjing, China; Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia.
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Maurer AH. Enhancing Scintigraphy for Evaluation of Gastric, Small Bowel, and Colonic Motility. Gastroenterol Clin North Am 2020; 49:499-517. [PMID: 32718567 DOI: 10.1016/j.gtc.2020.04.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This article reviews the latest enhancements in standards and technology for performing gastric emptying and associated small bowel and colon transit scintigraphic studies. It discusses how developments in appropriate use criteria, American Medical Association Current Procedural Terminology coding, and advanced commercial software permit clinicians to obtain more comprehensive physiologic studies of gastric, small bowel, and colon gastrointestinal motility disorders. It shows how gastrointestinal scintigraphy has expanded to permit assessments of global and regional (fundic and antral) gastric motility and how it permits a single study (whole-gut transit scintigraphy), including measurement of solid and liquid gastric emptying and small bowel and colon transit.
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Affiliation(s)
- Alan H Maurer
- Department of Radiology, Nuclear Medicine Section, Lewis Katz School of Medicine, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140, USA; Department of Medicine, Gastroenterology Section, Lewis Katz School of Medicine, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140, USA.
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Wu X, Yang Z, Li Z, Yang L, Wang X, Wang C, Gu J. Increased expression of hypoxia inducible factor-1 alpha and vascular endothelial growth factor is associated with diabetic gastroparesis. BMC Gastroenterol 2020; 20:216. [PMID: 32650726 PMCID: PMC7350597 DOI: 10.1186/s12876-020-01368-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 07/02/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Gastroparesis is a recognized complication of diabetes but its pathogenic mechanism incompletely understood. Our aim was to determine whether HIF-1α and VEGF are secreted from gastric tissue is a fundamental factor that drives diabetic gastroparesis. METHODS Diabetes was induced in Sprague-Dawley by a single intraperitoneal injection of 65 mg/kg streptozotocin. After 4 and 12 weeks, rats were euthanized for assaying body weight, blood glucose, gastric acid secretion and gastric emptying. Morphologic changes in gastric mucosa were observed by the light microscope. Expression of HIF-1α and VEGF were assessed using immunohistochemistry, RT-PCR and Western blot analyses. RESULTS Compared with control group, blood glucose were significantly increased and body weight were markedly decreased in streptozotocin-induced diabetes. Gastric emptying was significantly decreased in diabetic rats compared to the control group at different times. The number of parietal cells was obviously decreased, and vacuolated degeneration in diabetic rats. Gastric acid secretion in diabetic group was significantly decreased, and expression of HIF-1α and VEGF were significantly increased in the diabetic group. CONCLUSION These results indicated that overexpression of HIF-1α and VEGF in the gastric mucosa and played a pivotal role in the progression of diabetic gastroparesis.
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Affiliation(s)
- Xueping Wu
- Department of Anatomy, Histology and Embryology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
| | - Zhifang Yang
- Department of Physiology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
| | - Zhihong Li
- Department of Anatomy, Histology and Embryology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
| | - Ling Yang
- Department of Anatomy, Histology and Embryology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
| | - Xinyan Wang
- Department of Anatomy, Histology and Embryology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
| | - Congrong Wang
- Department of Anatomy, Histology and Embryology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
| | - Jun Gu
- Department of Anatomy, Histology and Embryology, Shanghai University of Medicine & Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai, China
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Abstract
Gastroparesis is characterized by delayed gastric emptying, with symptoms such as nausea, vomiting and abdominal pain, in the absence of mechanical obstruction. In most cases, it is idiopathic although diabetes mellitus is another leading cause. The physiology of gastric emptying is a complex process which is influenced by various inputs including the central nervous system, enteric nervous system and gut hormones. Developments in our understanding of gastroparesis have now demonstrated dysfunction in these systems, thus disrupting normal gastric emptying. Once mechanical obstruction is excluded, gastric scintigraphy remains the gold standard for diagnosis although wireless motility capsule and breath testing are alternative methods for diagnosis. Treatment for gastroparesis is challenging, and widely available therapies are often limited either by their poor evidence for efficacy or concerns over their long-term safety profile. Novel prokinetic agents have shown initial promise in clinical trials, and new endoscopic techniques such as gastric per-oral endoscopic myotomy are emerging. These new treatment modalities may provide an option in refractory gastroparesis with the adage of reduced morbidity compared to surgical treatments.
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Affiliation(s)
- A Sullivan
- Homerton University Hospital, London, UK
| | | | - A Ruban
- Department of Surgery and Cancer, Imperial College, London, UK.
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36
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Camilleri M, Lembo A, McCallum R, Tourkodimitris S, Kemps L, Miller MB, Bertelsen K, Iacob A. Overall safety of relamorelin in adults with diabetic gastroparesis: Analysis of phase 2a and 2b trial data. Aliment Pharmacol Ther 2020; 51:1139-1148. [PMID: 32301137 PMCID: PMC7318559 DOI: 10.1111/apt.15711] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Revised: 09/17/2019] [Accepted: 03/16/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Relamorelin, a pentapeptide ghrelin receptor agonist, accelerated gastric emptying significantly and improved symptoms in adults with diabetic gastroparesis in phase 2 trials. AIM To assess the safety and tolerability of relamorelin across phase 2 trials. METHODS Safety assessments in patients aged 18-75 years (weight, adverse events [AEs] and laboratory tests) from two randomised, double-blind phase 2 trials (NCT01571297, NCT02357420; results published previously) were reviewed descriptively. Analysis of covariance assessed treatment effect on glycated haemoglobin (HbA1c) and blood glucose post hoc. Phase 2a and 2b trial durations were, respectively, 4 weeks (relamorelin 10 µg once or twice daily [b.d.] or placebo b.d.) and 12 weeks (relamorelin 10, 30 or 100 µg or placebo b.d.) with 1- and 2-week, single-blind placebo run-ins. RESULTS Among 204 phase 2a and 393 phase 2b patients, respectively, 67% and 62% were female, and 88% and 89% had type 2 diabetes. Proportions of patients reporting serious AEs were similar across treatment groups, as were those with ≥1 treatment-emergent AE (TEAE). TEAE-related discontinuations were proportionally higher in relamorelin groups than placebo. Of 12 serious TEAEs in phase 2a, none occurred in >1 patient. In phase 2b, five serious TEAEs were reported in >1 patient, and one (100 µg) died (urosepsis), all unrelated to relamorelin. In phase 2b, increased HbA1c and fasting blood glucose levels were dose-related (P < 0.0001 and P = 0.0043, respectively). CONCLUSIONS Relamorelin showed acceptable safety and tolerability in phase 2 trials. Relamorelin may elevate blood glucose: this should be managed proactively in relamorelin-treated patients.
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Affiliation(s)
- Michael Camilleri
- Division of Gastroenterology and HepatologyMayo ClinicRochesterMNUSA
| | - Anthony Lembo
- Division of GastroenterologyBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA
| | - Richard McCallum
- Division of GastroenterologyTexas Tech University Health Sciences CenterEl PasoTXUSA
| | | | - Lara Kemps
- Clinical DevelopmentAllergan plcMadisonNJUSA
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Usai-Satta P, Bellini M, Morelli O, Geri F, Lai M, Bassotti G. Gastroparesis: New insights into an old disease. World J Gastroenterol 2020. [DOI: 10.3748/wjg.v26.i19.2332] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/24/2023] Open
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Usai-Satta P, Bellini M, Morelli O, Geri F, Lai M, Bassotti G. Gastroparesis: New insights into an old disease. World J Gastroenterol 2020; 26:2333-2348. [PMID: 32476797 PMCID: PMC7243643 DOI: 10.3748/wjg.v26.i19.2333] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Revised: 03/08/2020] [Accepted: 05/01/2020] [Indexed: 02/06/2023] Open
Abstract
Gastroparesis (Gp) is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction. Although this condition has been reported in the literature since the mid-1900s, only recently has there been renewed clinical and scientific interest in this disease, which has a potentially great impact on the quality of life. The aim of this review is to explore the pathophysiological, diagnostic and therapeutical aspects of Gp according to the most recent evidence. A comprehensive online search for Gp was carried out using MEDLINE and EMBASE. Gp is the result of neuromuscular abnormalities of the gastric motor function. There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes. As regards diagnostic approach, 99-Technetium scintigraphy is currently considered to be the gold standard for Gp. Its limits are a lack of standardization and a mild risk of radiation exposure. The C13 breath testing is a valid and safe alternative method. 13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits. The wireless motility capsule is a promising technique, but its use is limited by costs and scarce availability in many countries. Finally, therapeutic strategies are related to the clinical severity of Gp. In mild and moderate Gp, dietary modification and prokinetic agents are generally sufficient. Metoclopramide is the only drug approved by the Food and Drug Administration for Gp. However, other older and new prokinetics and antiemetics can be considered. As a second-line therapy, tricyclic antidepressants and cannabinoids have been proposed. In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed. In drug-unresponsive Gp patients some alternative strategies (endoscopic, electric stimulation or surgery) are available.
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Affiliation(s)
- Paolo Usai-Satta
- Department of Internal Medicine, Division of Gastroenterology, Brotzu Hospital, Cagliari 09124, Italy
| | - Massimo Bellini
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Olivia Morelli
- Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia Medical School, Perugia 06123, Italy
| | - Francesca Geri
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56122, Italy
| | - Mariantonia Lai
- Gastroenterology Unit, University of Cagliari, Monserrato 09042, Italy
| | - Gabrio Bassotti
- Gastroenterology and Hepatology Section, Department of Medicine, University of Perugia Medical School, Perugia 06123, Italy
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Wan Z, Song L, Hu L, Hu M, Lei X, Huang Y, Lv Y. Helicobacter pylori infection is associated with diabetes among Chinese adults. J Diabetes Investig 2020; 11:199-205. [PMID: 31207188 PMCID: PMC6944826 DOI: 10.1111/jdi.13102] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 04/23/2019] [Accepted: 06/10/2019] [Indexed: 12/16/2022] Open
Abstract
AIMS/INTRODUCTION Several epidemiological studies investigated the effect of Helicobacter pylori infection on diabetes, but the conclusions remained inconsistent. We aimed to explore the relationship between H. pylori infection and diabetes, as well as glycemic metabolism profiles. MATERIALS AND METHODS A cross-sectional study including 58,482 Chinese adults was carried out between January 2016 and December 2017. H. pylori infection was diagnosed by the 13 C-urea breath test. Multivariate regression analyses were carried out to evaluate the association of H. pylori infection with diabetes. RESULTS Of the 58,482 participants, 3,449 (5.9%) had diabetes. The H. pylori-positive participants had a higher rate of diabetes (7.3% vs 5.2%, P < 0.001), and higher levels of fasting plasma glucose (5.36 ± 1.12 mmol/L vs 5.28 ± 0.95 mmol/L, P < 0.001) and glycated hemoglobin A1c (5.63 ± 0.68% vs 5.57 ± 0.60%, P < 0.001) than the H. pylori negative group. Multivariate regression analyses showed that H. pylori infection was positively related to diabetes (odds ratio 1.25, 95% confidence interval 1.15-1.35). Among the H. pylori-positive participants, the elevated levels of fasting plasma glucose and glycated hemoglobin A1c were 0.033 mmol/L (95% confidence interval 0.016-0.049 mmol/L) and 0.024% (95% confidence interval 0.008-0.041%), respectively. Additionally, H. pylori infection was significantly related to diabetes in participants aged ≥44 years, but not in participants aged <44 years. CONCLUSIONS The present study showed that H. pylori infection is associated with diabetes among Chinese adults. More attention should be paid to adults with H. pylori infection for effective prevention of diabetes.
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Affiliation(s)
- Zhengce Wan
- Physical Examination CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Lulu Song
- Department of Maternal and Child HealthSchool of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Liu Hu
- Physical Examination CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Mei Hu
- Physical Examination CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiaomei Lei
- Physical Examination CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yuancheng Huang
- Physical Examination CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yongman Lv
- Physical Examination CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
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Asha MZ, Khalil SFH. Pharmacological Approaches to Diabetic Gastroparesis: A systematic review of randomised clinical trials. Sultan Qaboos Univ Med J 2019; 19:e291-e304. [PMID: 31897312 PMCID: PMC6930032 DOI: 10.18295/squmj.2019.19.04.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 07/10/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023] Open
Abstract
Pharmacological interventions of diabetic gastroparesis (DG) constitute an essential element of a patient’s management. This article aimed to systematically review the available pharmacological approaches of DG, including their efficacy and safety. A total of 24 randomised clinical trials (RCTs) that investigated the efficacy and/or safety of medications targeting DG symptoms were identified using several online databases. Their results revealed that metoclopramide was the only approved drug for accelerating gastric emptying and improving disease symptoms. However, this medication may have several adverse effects on the cardiovascular and nervous systems, which might be resolved with a new intranasal preparation. Acceptable alternatives are oral domperidone for patients without cardiovascular risk factors or intravenous erythromycin for hospitalised patients. Preliminary data indicated that relamorelin and prucalopride are novel candidates that have proven to be effective and safe. Future RCTs should be conducted based on unified guidelines using universal diagnostic modalities to reveal reliable and comprehensive outcomes.
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Affiliation(s)
- Mohammad Z Asha
- Department of Internal Medicine, Dr Mohamad Amine Zbeib Polyclinic, Doha, Qatar
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A Meta-Analysis of the Efficacy of Prokinetic Agents against Glycemic Control. Gastroenterol Res Pract 2019; 2019:3014973. [PMID: 31582970 PMCID: PMC6754912 DOI: 10.1155/2019/3014973] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 07/02/2019] [Accepted: 08/19/2019] [Indexed: 02/07/2023] Open
Abstract
Background Prokinetic agents are used in diabetic gastroparesis patients to improve gastric emptying and upper gastrointestinal (GI) symptoms. However, the efficacy of prokinetic agents against glycemic control is questionable. Therefore, we conducted a systemic review and meta-analysis to determine the efficacy of prokinetic agents against glycemic control. Methods Randomized controlled trials (RCTs) evaluating the effect of prokinetics were identified by searching PubMed, Embase, and the Cochrane Library databases until April 2018. The primary outcome was changes in the mean value of glycosylated hemoglobin (HbA1c), fasting blood sugar (FBS), and fasting serum insulin (FINS). The pooled standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated by evaluating the strength of the association. We used the random effect models to analyze these markers. The effects of each component of the prokinetic agents on glycemic control were separately analyzed. Results Five RCTs with 190 patients met the criteria and were included in the meta-analysis. There were statistically significant SMD between prokinetics and placebo-controlled groups with respect to the reduction of HbA1c (-1.141, 95% CI -1.843, -0.438; P < 0.01). No statistically significant differences were noted between the two groups for FBS (-1.270, 95% CI -2.613, -0.074; P = 0.06) and FINS (0.359, 95% CI -1.205~1.923; P = 0.65). Conclusions Prokinetics have a positive effect on glycemic control. Further large-scale prospective studies are needed.
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Abstract
This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.
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Affiliation(s)
- Adil E Bharucha
- Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Yogish C Kudva
- Division of Endocrinology. Mayo Clinic, Rochester, Minnesota
| | - David O Prichard
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Sheikh A, Anolik J, Maurer AH. Update on Serum Glucose and Metabolic Management of Clinical Nuclear Medicine Studies: Current Status and Proposed Future Directions. Semin Nucl Med 2019; 49:411-421. [PMID: 31470934 DOI: 10.1053/j.semnuclmed.2019.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Management of a patient's blood glucose or metabolism in nuclear medicine studies has become an integral aspect of daily work primarily due to the increasing use of F-18 flurodeoxyglucose (FDG) positron emission tomography (PET). Newer tracers such as F-18 Fluciclovine and C-11 Choline, are in theory subject to metabolic shifts and changes based on patients' insulin levels, and also require attention to achieving optimum patient preparation. Metabolic derangements can also affect other studies, such as gastric emptying (GE), the results of which are dependent upon the patient's blood glucose level during the time of imaging. The growing variety of diabetic medications has increased the complexity of the instructions which need to be given to patients. Current guidelines for patient preparation were developed in the past and have only slowly evolved with the introduction of newer oral medications. In addition to older insulin formulations newer formulations with different profiles of onset, duration, and consistency of action are being used. The wide spectrum of newer drugs now in use for treating diabetes has not been accompanied by any updated consensus on how to manage these drugs for imaging studies which require blood glucose level management. In this article we review these newer diabetes medications primarily to raise awareness of the changing landscape. Our focus will be on suggestions to optimize patient preparation and management for these studies. For each scenario, our suggestions will be given as summary proposals for best patient management. Our hope is that this discussion will stimulate multicenter studies to provide data to support new practice guidelines for metabolically dependent nuclear medicine procedures.
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Affiliation(s)
- Arif Sheikh
- Division of Nuclear Medicine; Department of Diagnostic, Molecular and Interventional Radiology, Mount Sinai Hospital, Icahn School of Medicine, New York, NY.
| | - Jonathan Anolik
- Section of Endocrinology, Department of Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA
| | - Alan H Maurer
- Section of Nuclear Medicine, Department of Radiology, Temple University Lewis Katz School of Medicine, Philadelphia, PA
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Shakhatreh M, Jehangir A, Malik Z, Parkman HP. Metoclopramide for the treatment of diabetic gastroparesis. Expert Rev Gastroenterol Hepatol 2019; 13:711-721. [PMID: 31314613 DOI: 10.1080/17474124.2019.1645594] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Introduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide. Areas covered: We searched PubMed using the key words 'metoclopramide', 'diabetic gastroparesis', and 'gastric emptying'. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible. Expert opinion: Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.
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Affiliation(s)
- Mohammed Shakhatreh
- a GI Section, Department of Medicine, Temple University School of Medicine , Philadelphia , PA , USA
| | - Asad Jehangir
- a GI Section, Department of Medicine, Temple University School of Medicine , Philadelphia , PA , USA
| | - Zubair Malik
- a GI Section, Department of Medicine, Temple University School of Medicine , Philadelphia , PA , USA
| | - Henry P Parkman
- a GI Section, Department of Medicine, Temple University School of Medicine , Philadelphia , PA , USA
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de Oliveira LCS, Telles PVN, E Sousa JFR, Cavalcante AKM, Wong DVT, Lima-Junior RC, Torres-Leal FL, Dos Santos AA, da Silva MTB. Influence of the physical exercise on decrease in the gastric emptying and alter appetite and food behavior in rats dexamethasone-treatment. Physiol Behav 2019; 209:112610. [PMID: 31299373 DOI: 10.1016/j.physbeh.2019.112610] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 06/05/2019] [Accepted: 07/08/2019] [Indexed: 02/06/2023]
Abstract
The chronic use of Dexamethasone (Dex) induced hyperglycemia and insulin resistance. On the other hand, physical exercise attenuates the symptoms induced by Dex in many physiological systems. However, the effect of the exercise on the changes in gastric motility induced by dexamethasone remains unknown. We hypothesized that low-intensity aerobic exercise modulates the metabolic effects induced by Dex-treatment by modifying the gastrointestinal function and feeding behavior in rats. Male rats were distributed into the following groups: Control (Ctrl), Dex (1.0 mg/kg, i.p.), Exercise (Ctrl + Exercise 5%) and (Dex1.0 + Exercise 5%). The exercise protocol was swimming for 5 consecutive days. We assessed the murinometric and nutritional indices, food intake, blood glucose by (ipGTT) and the gastric emptying rate of a liquid test meal were assessed in all rats. We observed a significant decrease (p < .05) in the gastric emptying in Dex1.0 group in relation to Ctrl group. The exercise prevented decrease in the gastric emptying (p < .05) in Dex1.0 + EX5% group when compared with Dex1.0 groups. The Dex1.0 group induced a significantly increase (p < .05) in glycaemia vs Ctrl group. The hyperglycemia was improving (p < .05) in the Dex1.0 + Ex5% compared with Dex1.0 groups. We observed a positive correlation (p < .05, and r = 0.7065) between gastric retention vs glycaemia in the Dex1.0 groups. The Dex1.0 reduced (p < .05) the body weight and altered body composition, promoting hypophagia. IL-6 increased (p < .05) at gastric fundus in Ex5% compared with Ctrl groups. In conclusion, the use of Dex1.0 decreases gastric emptying, promotes hyperglycemia and modifies feeding behavior. The low-intensity exercise prevents hyperglycemia, thus improving gastric dysmotility without improving the anthropometric parameters.
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Affiliation(s)
| | | | | | | | - Deysi Viviana Tenazoa Wong
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Roberto Cesar Lima-Junior
- Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Francisco Leonardo Torres-Leal
- Graduate Program in Food and Nutrition, Federal University of Piauí, Teresina, PI, Brazil; Graduate Program in Pharmacology, Federal University of Piauí, Teresina, PI, Brazil
| | - Armenio Aguiar Dos Santos
- Graduate Program in Medical Sciences, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil
| | - Moisés Tolentino Bento da Silva
- Graduate Program in Food and Nutrition, Federal University of Piauí, Teresina, PI, Brazil; Department of Physical Education, Federal University of Piauí, Teresina, PI, Brazil; Graduate Program in Pharmacology, Federal University of Piauí, Teresina, PI, Brazil.
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Characterizing Abdominal Pain in Patients With Gastroparesis Into Neuropathic and Nociceptive Components. J Clin Gastroenterol 2019; 53:427-433. [PMID: 29782470 DOI: 10.1097/mcg.0000000000001059] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION The cause of abdominal pain (AP) in gastroparesis (Gp) is often not known; hence, its treatment can be challenging. Preoccupation with or increased attention (hypervigilance) to pain is associated with perceived pain severity and psychosocial disability. The aims of this study were to (1) characterize AP in Gp patients into neuropathic and nociceptive pain components; (2) assess these patients for hypervigilance to pain. MATERIALS AND METHODS Gp patients with AP as an important symptom, seen from June 2017 to November 2017 were given validated questionnaires to characterize their AP. Carnett's sign (worsened AP/tenderness on head/shoulder lift and/or leg lift) was assessed on examination. RESULTS Of 32 patients (87% females), 20 had idiopathic Gp, and 9 had diabetic Gp. AP severity using Patient Assessment of Gastrointestinal Symptoms averaged 4.3±0.2 (standard error of mean) for upper AP and 2.3±0.3 for lower AP. AP was typically located in epigastrium (53.1%), and described as sharp (75%). Eleven patients (35.5%) met criteria for neuropathic pain on Neuropathic Pain Questionnaire. Twenty patients (62.5%) had positive Carnett's sign suggesting somatic pain. Fifteen patients (48.4%) were hypervigilant to pain on Pain Vigilance and Awareness Questionnaire. CONCLUSIONS Of Gp patients with AP, over one third have a neuropathic component to their pain whereas nearly two thirds have characteristics of somatic pain. Almost half of the Gp patients with AP are hypervigilant to pain. Determining the underlying cause of AP and hypervigilance to pain in Gp patients may assist in devising appropriate treatment strategies.
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Chakraborty S, Halland M, Burton D, Desai A, Neja B, Low P, Singer W, Camilleri M, Zinsmeister AR, Bharucha AE. GI Dysfunctions in Diabetic Gastroenteropathy, Their Relationships With Symptoms, and Effects of a GLP-1 Antagonist. J Clin Endocrinol Metab 2019; 104:1967-1977. [PMID: 30358871 PMCID: PMC6467444 DOI: 10.1210/jc.2018-01623] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 10/19/2018] [Indexed: 12/15/2022]
Abstract
CONTEXT Delayed gastric emptying (GE) is common but often asymptomatic in diabetes. The relationship between symptoms, glycemia, and neurohormonal functions, including glucagonlike peptide 1 (GLP-1), are unclear. OBJECTIVES To assess whether GE disturbances, symptoms during a GE study, and symptoms during enteral lipid infusion explain daily symptoms and whether GLP-1 mediates symptoms during enteral lipid infusion. DESIGN In this randomized controlled trial, GE, enteral lipid infusion, gastrointestinal (GI) symptoms during these assessments, autonomic functions, glycosylated hemoglobin (HbA1c), and daily GI symptoms (2-week Gastroparesis Cardinal Symptom Index diary) were evaluated. During enteral lipid infusion, participants received the GLP-1 antagonist exendin 9-39 or placebo. SETTING Single tertiary referral center. PARTICIPANTS 24 healthy controls and 40 patients with diabetic gastroenteropathy. MAIN OUTCOME MEASURES GE, symptoms during enteral lipid infusion, and the effect of exendin 9-39 on the latter. RESULTS In patients, GE was normal (55%), delayed (33%), or rapid (12%). During lipid infusion, GI symptoms tended to be greater (P = 0.06) in patients with diabetes mellitus (DM) than controls; exendin 9-39 did not affect symptoms. The HbA1c was inversely correlated with the mean symptom score during the GE study (r = -0.46, P = 0.003) and lipid infusion (r = -0.47, P < 0.01). GE and symptoms during GE study accounted for 40% and 32%, respectively, of the variance in daily symptom severity and quality of life. CONCLUSIONS In DM gastroenteropathy, GE and symptoms during a GE study explain daily symptoms. Symptoms during enteral lipid infusion were borderline increased but not reduced by a GLP-1 antagonist.
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Affiliation(s)
| | - Magnus Halland
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Duane Burton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Anshuman Desai
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Bridget Neja
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Phillip Low
- Department of Neurology, Mayo Clinic, Rochester, Minnesota
| | | | - Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Alan R Zinsmeister
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
| | - Adil E Bharucha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Adams JD, Treiber G, Hurtado MD, Laurenti MC, Dalla Man C, Cobelli C, Rizza RA, Vella A. Increased Rates of Meal Absorption Do Not Explain Elevated 1-Hour Glucose in Subjects With Normal Glucose Tolerance. J Endocr Soc 2018; 3:135-145. [PMID: 30591957 PMCID: PMC6302905 DOI: 10.1210/js.2018-00222] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 11/16/2018] [Indexed: 01/12/2023] Open
Abstract
Context In subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT), glucose concentrations >155 mg/dL 1 hour after 75 g of oral glucose predict increased risk of progression to diabetes. Recently, it has been suggested that the mechanism underlying this abnormality is increased gut absorption of glucose. Objective We sought to determine the rate of systemic appearance of meal-derived glucose in subjects classified by their 1-hour glucose after a 75-g oral glucose challenge. Design This was a cross-sectional study. Participating subjects underwent a 75-g oral glucose challenge and a labeled mixed meal test. Setting An inpatient clinical research unit at an academic medical center. Participants Thirty-six subjects with NFG/NGT participated in this study. Interventions Subjects underwent an oral glucose tolerance test. Subsequently, they underwent a labeled mixed meal to measure fasting and postprandial glucose metabolism. Main Outcome Measures We examined β-cell function and the rate of meal appearance (Meal Ra) in NFG/NGT subjects. Subsequently, we examined the relationship of peak postchallenge glucose with Meal Ra and indices of β-cell function. Results Peak glucose concentrations correlated inversely with β-cell function. No relationship of Meal Ra with peak postchallenge glucose concentrations was observed. Conclusion In subjects with NFG/NGT, elevated 1-hour peak postchallenge glucose concentrations reflect impaired β-cell function rather than increased systemic meal appearance.
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Affiliation(s)
- J D Adams
- Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, Minnesota
| | - Gerlies Treiber
- Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Maria Daniela Hurtado
- Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, Minnesota
| | - Marcello C Laurenti
- Department of Information Engineering, Università di Padova, 36131 Padova, Italy
| | - Chiara Dalla Man
- Department of Information Engineering, Università di Padova, 36131 Padova, Italy
| | - Claudio Cobelli
- Department of Information Engineering, Università di Padova, 36131 Padova, Italy
| | - Robert A Rizza
- Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, Minnesota
| | - Adrian Vella
- Division of Endocrinology, Diabetes, and Metabolism, Mayo Clinic, Rochester, Minnesota
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Camilleri M, Chedid V, Ford AC, Haruma K, Horowitz M, Jones KL, Low PA, Park SY, Parkman HP, Stanghellini V. Gastroparesis. Nat Rev Dis Primers 2018; 4:41. [PMID: 30385743 DOI: 10.1038/s41572-018-0038-z] [Citation(s) in RCA: 231] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastroparesis is a disorder characterized by delayed gastric emptying of solid food in the absence of a mechanical obstruction of the stomach, resulting in the cardinal symptoms of early satiety, postprandial fullness, nausea, vomiting, belching and bloating. Gastroparesis is now recognized as part of a broader spectrum of gastric neuromuscular dysfunction that includes impaired gastric accommodation. The overlap between upper gastrointestinal symptoms makes the distinction between gastroparesis and other disorders, such as functional dyspepsia, challenging. Thus, a confirmed diagnosis of gastroparesis requires measurement of delayed gastric emptying via an appropriate test, such as gastric scintigraphy or breath testing. Gastroparesis can have idiopathic, diabetic, iatrogenic, post-surgical or post-viral aetiologies. The management of gastroparesis involves: correcting fluid, electrolyte and nutritional deficiencies; identifying and treating the cause of delayed gastric emptying (for example, diabetes mellitus); and suppressing or eliminating symptoms with pharmacological agents as first-line therapies. Several novel pharmacologic agents and interventions are currently in the pipeline and show promise to help tailor individualized therapy for patients with gastroparesis.
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Affiliation(s)
- Michael Camilleri
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
| | - Victor Chedid
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Alexander C Ford
- Leeds Gastroenterology Institute, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK
| | - Ken Haruma
- Department of Internal Medicine 2, General Medical Center, Kawasaki Medical School, Okayama, Japan
| | - Michael Horowitz
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia
| | - Phillip A Low
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Seon-Young Park
- Division of Gastroenterology, Chonnam National University School of Medicine, Gwangju, Republic of Korea
| | - Henry P Parkman
- GI Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Vincenzo Stanghellini
- Department of Digestive Diseases, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy
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Prevost GA, Odermatt M, Furrer M, Villiger P. Postoperative morbidity of complete mesocolic excision and central vascular ligation in right colectomy: a retrospective comparative cohort study. World J Surg Oncol 2018; 16:214. [PMID: 30376849 PMCID: PMC6208021 DOI: 10.1186/s12957-018-1514-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2018] [Accepted: 10/17/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND To investigate morbidity and mortality following complete mesocolic excision (CME) and central vascular ligation (CVL) in patients undergoing right colectomy. METHODS Data from consecutive patients undergoing elective right colectomy at a university-affiliated referral centre were retrospectively analysed. Patients who underwent conventional right-sided colonic cancer surgery (January 2001-April 2009, n = 84) were compared to patients who underwent CME/CVL (May 2009-January 2015, n = 71). The primary end point was anastomotic leak. Secondary end points were delayed gastric emptying, severe respiratory failure, mortality and length of hospital stay. RESULTS No significant difference was found in the rate of anastomotic leak (1.2% in the conventional versus 5.6% in the CME/CVL group, p = 0.108). Patients in the CME/CVL group had a higher 90-day mortality rate (7.0% versus 0.0%, p = 0.019). Four out of five deceased patients suffered from aspiration with consecutive respiratory failure. There was a tendency towards delayed gastric emptying in the CME/CVL group (12.7% versus 7.1%, p = 0.246). Clavien-Dindo complication grades ≥ 2 were similar in both groups with 16 (19%) in the conventional and 15 (21.1%) in the CME/CVL group (p = 0.747). CME/CVL patients had a shorter mean length of stay with 11 versus 14 days (p < 0.001). CONCLUSIONS Complete mesocolic excision with central vascular ligation in right colectomy seems to have a higher aspiration rate leading to severe respiratory failure and to higher mortality compared to conventional resection methods. Patient selection for this procedure may therefore be crucial.
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Affiliation(s)
- Gian Andrea Prevost
- Department of Surgery, Kantonsspital Graubünden, Loëstrasse 170, CH-7000, Chur, Switzerland. .,Private University of the Principality of Liechtenstein, Triesen, Principality of Liechtenstein.
| | - Manfred Odermatt
- Department of Surgery, Kantonsspital Graubünden, Loëstrasse 170, CH-7000, Chur, Switzerland
| | - Markus Furrer
- Department of Surgery, Kantonsspital Graubünden, Loëstrasse 170, CH-7000, Chur, Switzerland.,Private University of the Principality of Liechtenstein, Triesen, Principality of Liechtenstein
| | - Peter Villiger
- Department of Surgery, Kantonsspital Graubünden, Loëstrasse 170, CH-7000, Chur, Switzerland
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