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Kornum DS, Krogh K, Keller J, Malagelada C, Drewes AM, Brock C. Diabetic gastroenteropathy: a pan-alimentary complication. Diabetologia 2025; 68:905-919. [PMID: 39934370 PMCID: PMC12021976 DOI: 10.1007/s00125-025-06365-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/07/2025] [Indexed: 02/13/2025]
Abstract
Autonomic neuropathy contributes to the pathophysiology of diabetic gastroenteropathy, which impacts the entire gastrointestinal tract alongside pancreatic and gallbladder functions. This is evident in the widespread morphological remodelling of the enteric nervous system, smooth muscle cells, interstitial cells of Cajal and vascular supply, causing pan-enteric motor, sensory and secretory disturbances. The gastrointestinal symptoms caused by these changes are often burdensome and non-specific and frequently coexist with poor glycaemic management and even malnutrition, impacting quality of life negatively. The Gastroparesis Cardinal Symptom Index and the Gastrointestinal Symptom Rating Scale are validated questionnaires for assessing gastrointestinal symptoms. However, clinical supplementary objective measures are essential. Transit time assessments are frequently used and typically evaluated using gastric emptying scintigraphy, breath tests or colonic radiopaque markers, but they cannot measure contractile activity or fluid transport. The primary treatment goals are to prevent further disease progression and to obtain symptomatic relief. Treatments include improved glycaemic management and dietary modifications, while pharmacological treatments target gastrointestinal symptoms, small intestinal bacterial overgrowth and exocrine pancreatic insufficiency. Invasive interventions may involve gastric peroral pyloromyotomy or the implantation of a gastric neurostimulator to manage pharmacologically refractory gastroparesis. This review describes the prevalence, pathophysiology, clinical presentation, assessment and treatment of diabetic gastrointestinal dysfunction within each segment of the gastrointestinal tract and directly connected exocrine organs.
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Affiliation(s)
- Ditte S Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jutta Keller
- Department of Internal Medicine, Israelitic Hospital, Academic Hospital University of Hamburg, Hamburg, Germany
| | - Carolina Malagelada
- Digestive System Research Unit, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.
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Baroud S, Kerbage A, Patel A, Horton A, Sims A, Patel D, Mehta K, Kapil N, Kavitt R, Rangan V, Yu Y, Shibli F, Song G, Fass R. Ineffective esophageal motility is associated with diabetes mellitus end organ complications. Neurogastroenterol Motil 2024; 36:e14826. [PMID: 38873936 DOI: 10.1111/nmo.14826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 04/24/2024] [Accepted: 05/15/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Diabetes Mellitus (DM) is known to induce a wide range of harmful effects on several organs, notably leading to ineffective esophageal motility (IEM). However, the relationship between DM and IEM is not fully elucidated. We aimed to determine the relationship between DM and IEM and to evaluate the impact of DM's end organ complications on IEM severity. METHODS A multicenter cohort study of consecutive patients undergoing high-resolution esophageal manometry (HREM) was performed. We reviewed medical records of patients diagnosed with IEM using HREM, encompassing data on demographics, DM history, antidiabetic and other medications as well as comorbidities. KEY RESULTS Two hundred and forty six subjects met the inclusion criteria. There was no significant difference in any of the HREM parameters between diabetics and nondiabetics. Out of 246 patients, 92 were diabetics. Diabetics with neuropathy presented a significantly lower distal contractile integral (DCI) value compared to those without neuropathy (248.2 ± 226.7 mmHg·cm·sec vs. 375.6 ± 232.4 mmHg·cm·sec; p = 0.02) Similarly, the DCI was lower in diabetics with retinopathy compared to those without retinopathy (199.9 ± 123.1 mmHg·cm·sec vs. 335.4 ± 251.7 mmHg·cm·sec; p = 0.041). Additionally, a significant difference was observed in DCI values among DM patients with ≥2 comorbidities compared to those without comorbidities (224.8 ± 161.0 mmHg·cm·sec vs. 394.2 ± 243.6 mmHg·cm·sec; p = 0.025). Around 12.6% of the variation in DCI could be explained by its linear relationship with hemoglobin A1c (HbA1c), with a regression coefficient (β) of -55.3. CONCLUSION & INFERENCES DM is significantly associated with IEM in patients with neuropathy, retinopathy, or multiple comorbidities. These results are pivotal for tailoring patient-specific management approaches.
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Affiliation(s)
- Serge Baroud
- Division of Gastroenterology and Hepatology, Metro Health Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Anthony Kerbage
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Amit Patel
- Duke University School of Medicine and the Durham Veterans Affairs Medical Center, Durham, North Carolina, USA
| | - Anthony Horton
- Duke University School of Medicine and the Durham Veterans Affairs Medical Center, Durham, North Carolina, USA
| | - Ariel Sims
- The University of Chicago Medicine, Chicago, Illinois, USA
| | - Dhyanesh Patel
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Kurren Mehta
- Duke University School of Medicine and the Durham Veterans Affairs Medical Center, Durham, North Carolina, USA
| | - Neil Kapil
- Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Robert Kavitt
- The University of Chicago Medicine, Chicago, Illinois, USA
| | - Vikram Rangan
- Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Yue Yu
- Division of Life Sciences and Medicine, Department of Gastroenterology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China
| | - Fahmi Shibli
- Division of Gastroenterology and Hepatology, Metro Health Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Gengqing Song
- Division of Gastroenterology and Hepatology, Metro Health Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, Metro Health Medical Center, The Esophageal and Swallowing Center, Case Western Reserve University, Cleveland, Ohio, USA
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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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Kornum DS, Terkelsen AJ, Bertoli D, Klinge MW, Høyer KL, Kufaishi HHA, Borghammer P, Drewes AM, Brock C, Krogh K. Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives. J Clin Med 2021; 10:jcm10071392. [PMID: 33807256 PMCID: PMC8037288 DOI: 10.3390/jcm10071392] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/25/2021] [Accepted: 03/27/2021] [Indexed: 11/16/2022] Open
Abstract
The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.
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Affiliation(s)
- Ditte S. Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
- Correspondence:
| | - Astrid J. Terkelsen
- Department of Neurology, Aarhus University Hospital, DK8200 Aarhus, Denmark;
| | - Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
| | - Mette W. Klinge
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
| | - Katrine L. Høyer
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
| | - Huda H. A. Kufaishi
- Steno Diabetes Centre Copenhagen, Gentofte Hospital, DK2820 Gentofte, Denmark;
| | - Per Borghammer
- Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, DK8200 Aarhus, Denmark;
| | - Asbjørn M. Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
- Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
- Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
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Wu PI, Sloan JA, Kuribayashi S, Gregersen H. Impedance in the evaluation of the esophagus. Ann N Y Acad Sci 2020; 1481:139-153. [PMID: 32557676 DOI: 10.1111/nyas.14408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/09/2020] [Accepted: 05/14/2020] [Indexed: 12/16/2022]
Abstract
The aim of this paper is to review esophageal electrical impedance technologies and to discuss the use of these technologies for physiological measurements, diagnostics, and therapy of esophageal disease. In order to develop a better understanding of the pathophysiology of and improve the diagnosis of esophageal disorders, such as gastroesophageal reflux disease (GERD) and achalasia, several new diagnostic tests, including intraluminal impedance, esophageal mucosal impedance, and the functional luminal imaging probe, have been developed. These technologies have proven valuable for assessment of the esophagus in recent years. They provide information on esophageal flow properties, mucosal integrity, lumen shape, and distensibility in esophageal disorders, in particular for GERD and achalasia. Despite their promise and novel clinical studies, the potential of these technologies has been far from realized. New multidisciplinary approaches will contribute to our understanding and interpretation of esophageal impedance data and disease mechanisms.
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Affiliation(s)
- Peter I Wu
- Department of Gastroenterology and Hepatology, St George Hospital, University of New South Wales, Sydney, New South Wales, Australia
| | - Joshua A Sloan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shiko Kuribayashi
- Department of Gastroenterology and Hepatology, Gunma University Hospital, Maebashi, Japan
| | - Hans Gregersen
- GIOME, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
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Jiang H, Zhao J, Liao D, Wang G, Gregersen H. Esophageal stress softening recovery is altered in STZ-induced diabetic rats. J Biomech 2019; 92:126-136. [DOI: 10.1016/j.jbiomech.2019.05.042] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 05/27/2019] [Accepted: 05/27/2019] [Indexed: 12/29/2022]
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Borbély Y, Schaffner E, Zimmermann L, Huguenin M, Plitzko G, Nett P, Kröll D. De novo gastroesophageal reflux disease after sleeve gastrectomy: role of preoperative silent reflux. Surg Endosc 2018; 33:789-793. [PMID: 30003346 DOI: 10.1007/s00464-018-6344-4] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 07/06/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has become the most frequently performed bariatric procedure to date. However, LSG is known to worsen pre-operative and result in de novo gastroesophageal reflux disease (GERD). Pre-operative evaluation reveals a high percentage of silent GERD of so far unknown influence on post-operative GERD. METHODS Prospective data of patients undergoing primary LSG between 01/2012 and 12/2015 were evaluated. Pre-operative GERD-specific evaluation consisted of validated questionnaires, upper endoscopy, 24 h-pH-manometry, and esophagograms. Patients were followed-up with questionnaires every 6 months, upper endoscopies after 1 year and 24 h-pH-metry after 2 years. Silent GERD was defined as esophagitis grade > B and/or abnormal esophageal acid exposure in absence of symptoms. LSG was performed over a 32F bougie, hiatal hernias > 1 cm were addressed with posterior hiatoplasty. Excluded were patients with hiatal hernias > 4 cm, patients with incorrect anatomy (stenosis, fundus too large) and conversion to RYGB for early leaks. RESULTS 222 patients were included. Mean follow-up was 32 ± 16 months, mean preoperative body mass index 49.6 ± 7.2 kg/m2. 116 patients (52%) presented with post-operative GERD-symptoms, of which 85 (73%) had de novo symptoms. Of those, 48 (of 85, 56%) had no preoperative GERD and 37 (of 85, 44%) silent GERD. 57 patients (26%) had neither pre- nor post-operative GERD, 7 (3%) had silent pre-operative and no postop GERD, and in 19 patients (9%) GERD was cured with LSG. 31 patients (14%) stayed symptomatic. Of 56 patients (25%) with pre-operative silent GERD, 37 (of 54, 66%) became symptomatic. CONCLUSION LSG leads to a considerable rate of post-operative GERD. De novo-GERD consist of around half of pre-operative silent GERD and completely de novo-GERD. Most patients with pre-operative silent GERD became symptomatic.
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Affiliation(s)
- Yves Borbély
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland.
| | - Esther Schaffner
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Lara Zimmermann
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Michael Huguenin
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Gabriel Plitzko
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Philipp Nett
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
| | - Dino Kröll
- Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
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Du YT, Rayner CK, Jones KL, Talley NJ, Horowitz M. Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management. Diabetes Care 2018; 41:627-637. [PMID: 29463666 DOI: 10.2337/dc17-1536] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 12/07/2017] [Indexed: 02/05/2023]
Abstract
If you haven't measured something, you really don't know much about it.-Karl Pearson (attributed)Gastrointestinal (GI) symptoms represent an important and often unappreciated cause of morbidity in diabetes, although the significance of this burden across the spectrum of patients and the underlying pathophysiology, including the relationship of symptoms with glycemic control, remain poorly defined. The relevance of GI symptoms and the necessity for their accurate assessment have increased with the greater focus on the gut as a therapeutic target for glucose lowering. This review addresses the prevalence, assessment, pathogenesis, and management of GI symptoms in diabetes, beginning with broad principles and then focusing on specific segments of the GI tract. We initially performed a literature search of PubMed by using synonyms and combinations of the following search terms: "gastrointestinal symptoms", "diabetes", "prevalence", "pathogenesis", "diagnosis", and "management". We restricted the search results to English only. Review papers and meta-analyses are presented as the highest level of evidence where possible followed by randomized controlled trials, uncontrolled trials, retrospective and observational data, and expert opinion.
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Affiliation(s)
- Yang T Du
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Christopher K Rayner
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
- National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
- National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
| | - Nicholas J Talley
- Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
- Karolinska Institute, Stockholm, Sweden
| | - Michael Horowitz
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
- National Health and Medical Research Council Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
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Abstract
BACKGROUND Diabetes mellitus can cause various gastrointestinal symptoms. Assessment of esophageal dysmotility in diabetic patients has been scarcely studied. The aim of this study was to determine the esophageal motor characteristics of diabetic versus nondiabetic patients who present with dysphagia. METHODS High-resolution esophageal manometries (HREMs) of 83 diabetic patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2 medical centers were included in this study. Demographic information, medical comorbidities, and medication usage were recorded for each patient in a single registry. HREM of each patient was evaluated and the different functional parameters were recorded. KEY RESULTS Overall, 46% of diabetic patients were found to have an esophageal motor disorder. Diabetic patients with dysphagia were more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared with nondiabetic patients. Among diabetic patients, those being treated with insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5% vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin. Among diabetic patients, those with abnormal manometry were more likely to demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend toward increased incidence of esophagogastric junction outflow obstruction in diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic patients. CONCLUSIONS Nearly half of diabetic patients with dysphagia have some type of an esophageal motility disorder. Diabetic retinopathy and the use of insulin are predictive of esophageal motor abnormalities among diabetic patients.
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Gregersen H, Liao D, Brasseur JG. The Esophagiome: concept, status, and future perspectives. Ann N Y Acad Sci 2016; 1380:6-18. [PMID: 27570939 DOI: 10.1111/nyas.13200] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 07/13/2016] [Accepted: 07/14/2016] [Indexed: 12/23/2022]
Abstract
The term "Esophagiome" is meant to imply a holistic, multiscale treatment of esophageal function from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. The development and application of multiscale mathematical models of esophageal function are central to the Esophagiome concept. These model elements underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease by quantitatively contrasting normal and pathophysiological function. Functional models incorporate anatomical details with sensory-motor properties and functional responses, especially related to biomechanical functions, such as bolus transport and gastrointestinal fluid mixing. This brief review provides insight into Esophagiome research. Future advanced models can provide predictive evaluations of the therapeutic consequences of surgical and endoscopic treatments and will aim to facilitate clinical diagnostics and treatment.
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Affiliation(s)
- Hans Gregersen
- GIOME, College of Bioengineering, Chongqing University, China. .,GIOME, Department of Surgery, Prince of Wales Hospital, College of Medicine, Chinese University of Hong Kong, Hong Kong SAR.
| | - Donghua Liao
- GIOME Academy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - James G Brasseur
- Aerospace Engineering Sciences, University of Colorado, Boulder, Colorado
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12
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Ravages of Diabetes on Gastrointestinal Sensory-Motor Function: Implications for Pathophysiology and Treatment. Curr Gastroenterol Rep 2016; 18:6. [PMID: 26768896 DOI: 10.1007/s11894-015-0481-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Symptoms related to functional and sensory abnormalities are frequently encountered in patients with diabetes mellitus. Most symptoms are associated with impaired gastric and intestinal function. In this review, we discuss basic concepts of sensory-motor dysfunction and how they relate to clinical findings and gastrointestinal abnormalities that are commonly seen in diabetes. In addition, we review techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of sensory-motor function. Such technological advances, while not readily available in the clinical setting, may facilitate stratification and individualization of therapy in diabetic patients in the future. Unraveling the structural, mechanical, and sensory remodeling in diabetes disease is based on a multidisciplinary approach that can bridge the knowledge from a variety of scientific disciplines. The final goal is to increase the understanding of the damage to GI structures and to sensory processing of symptoms, in order to assist clinicians with developing an optimal mechanics based treatment.
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Zhao J, Gregersen H. Diabetes-induced mechanophysiological changes in the esophagus. Ann N Y Acad Sci 2016; 1380:139-154. [PMID: 27495976 DOI: 10.1111/nyas.13180] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 06/17/2016] [Accepted: 06/20/2016] [Indexed: 12/13/2022]
Abstract
Esophageal disorders are common in diabetes mellitus (DM) patients. DM induces mechanostructural remodeling in the esophagus of humans and animal models. The remodeling is related to esophageal sensorimotor abnormalities and to symptoms frequently encountered by DM patients. For example, gastroesophageal reflux disease (GERD) is a common disorder associated with DM. This review addresses diabetic remodeling of esophageal properties and function in light of the Esophagiome, a scientifically based modeling effort to describe the physiological dynamics of the normal, intact esophagus built upon interdisciplinary approaches with applications for esophageal disease. Unraveling the structural, biomechanical, and sensory remodeling of the esophagus in DM must be based on a multidisciplinary approach that can bridge the knowledge from a variety of scientific disciplines. The first focus of this review is DM-induced morphodynamic and biomechanical remodeling in the esophagus. Second, we review the sensorimotor dysfunction in DM and how it relates to esophageal remodeling. Finally, we discuss the clinical consequences of DM-induced esophageal remodeling, especially in relation to GERD. The ultimate aim is to increase the understanding of DM-induced remodeling of esophageal structure and sensorimotor function in order to assist clinicians to better understand the esophageal disorders induced by DM and to develop better treatments for those patients.
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Affiliation(s)
- Jingbo Zhao
- Giome Academia, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
| | - Hans Gregersen
- GIOME, Department of Surgery, Prince of Wales Hospital and Chinese University of Hong Kong, Shatin, Hong Kong SAR.,GIOME, College of Bioengineering, Chongqing University, Chongqing, China
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Drewes AM, Søfteland E, Dimcevski G, Farmer AD, Brock C, Frøkjær JB, Krogh K, Drewes AM. Brain changes in diabetes mellitus patients with gastrointestinal symptoms. World J Diabetes 2016; 7:14-26. [PMID: 26839652 PMCID: PMC4724575 DOI: 10.4239/wjd.v7.i2.14] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Revised: 09/14/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system (CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal (GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testing mainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes, especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation.
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Roman S, Marjoux S, Thivolet C, Mion F. Oesophageal function assessed by high-resolution manometry in patients with diabetes and inadequate glycaemic control. Diabet Med 2014; 31:1452-9. [PMID: 24766201 DOI: 10.1111/dme.12476] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 12/19/2013] [Accepted: 04/22/2014] [Indexed: 12/12/2022]
Abstract
AIMS To describe oesophageal function in people with diabetes and poor glycaemic control using oesophageal high-resolution manometry and to compare the result between control subjects and patients with gastro-oesophageal reflux disease. METHODS The results of oesophageal high-resolution manometry and a gastric emptying test were reviewed in 20 patients with diabetes. The high-resolution manometry protocol consisted of 5-ml swallows of water and multiple swallows of water. Oesophageal motility disorders were classified according to the Chicago classification system. The occurence of multiphasic contractions and intragastric and intrabolus pressures were measured. High-resolution manometry results were compared between 10 control subjects and 20 patients with gastro-oesophageal reflux disease. Data were expressed as medians and compared using Mann-Whitney and chi-squared tests. RESULTS Oesophageal motility disorders were similarly distributed between the groups. Multiphasic contractions occurred more frequently in patients with diabetes than in those with gastro-oesophageal reflux disease (60 vs 20% per patient; P<0.01) and were not observed in control subjects. Gastric emptying was delayed in six patients with diabetes and did not correlate with symptoms or oesophageal motility disorders. Intrabolus pressure was higher in patients with diabetes and gastroparesis than in those without (17 vs 10 mmHg; P=0.02) and correlated with intragastric pressure (r=0.46, P<0.01). During multiple swallows of water, oesophageal contractile activity was incompletely inhibited in 83% of patients with diabetes and gastroparesis vs 9% without (P<0.01). Oesophageal function and gastric emptying were not influenced by fasting glycaemia. CONCLUSIONS Patients with gastroparesis might present with impaired inhibition of contractile activity during multiple swallows of water. Increased intrabolus pressure is suggestive of delayed oesophageal clearance as a consequence of gastroparesis.
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Affiliation(s)
- S Roman
- Digestive Physiology, Hospices Civils de Lyon, Lyon, France; Digestive Physiology, Lyon I University, Lyon, France; Inserm U1032, LabTAU, Lyon, France
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Olausson EA, Brock C, Drewes AM, Grundin H, Isaksson M, Stotzer P, Abrahamsson H, Attvall S, Simrén M. Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms. Neurogastroenterol Motil 2013; 25:e224-32. [PMID: 23316944 DOI: 10.1111/nmo.12075] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin-treated diabetes. METHODS On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire. KEY RESULTS We included 115 patients with insulin-treated diabetes (median age 53, range 21-69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P < 0.0001). Eighty-three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P < 0.001) and nausea/vomiting (r = 0.30; P < 0.001). CONCLUSIONS & INFERENCES A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.
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Affiliation(s)
- E A Olausson
- Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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