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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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2
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Cruz-Muñoz JR, Valdez-Morales EE, Barajas-Espinosa A, Barrios-García T, Liñán-Rico A, Guerrero-Alba R. Gene expression alterations of purinergic signaling components in obesity-associated intestinal low-grade inflammation in type 2 diabetes. Purinergic Signal 2024; 20:629-643. [PMID: 38587723 PMCID: PMC11555165 DOI: 10.1007/s11302-024-10006-1] [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: 08/17/2023] [Accepted: 03/26/2024] [Indexed: 04/09/2024] Open
Abstract
Intestinal low-grade inflammation induced by a high-fat diet has been found to detonate chronic systemic inflammation, which is a hallmark of obesity, and precede the apparition of insulin resistance, a key factor for developing type 2 diabetes (T2D). Aberrant purinergic signaling pathways have been implicated in the pathogenesis of inflammatory bowel disease and other gastrointestinal diseases. However, their role in the gut inflammation associated with obesity and T2D remains unexplored. C57BL/6 J mice were fed a cafeteria diet for 21 weeks and received one injection of streptozotocin in their sixth week into the diet. The gene expression profile of purinergic signaling components in colon tissue was assessed by RT-qPCR. Compared to control mice, the treated group had a significant reduction in colonic length and mucosal and muscular layer thickness accompanied by increased NF-κB and IL-1β mRNA expression. Furthermore, colonic P2X2, P2X7, and A3R gene expression levels were lower, while the P2Y2, NT5E, and ADA expression levels increased. In conclusion, these data suggest that these purinergic signaling components possibly play a role in intestinal low-grade inflammation associated with obesity and T2D and thus could represent a novel therapeutic target for the treatment of the metabolic complications related to these diseases.
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Affiliation(s)
- José R Cruz-Muñoz
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México
| | - Eduardo E Valdez-Morales
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México
| | - Alma Barajas-Espinosa
- Escuela Superior de Huejutla, Universidad Autónoma del Estado de Hidalgo, Huejutla de Reyes, Hidalgo, México
| | - Tonatiuh Barrios-García
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México
| | - Andrómeda Liñán-Rico
- Centro Universitario de Investigaciones Biomédicas. Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCYT), Universidad de Colima, Colima, México.
| | - Raquel Guerrero-Alba
- Departamento de Fisiología y Farmacología, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Aguascalientes, Ags, México.
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Whorwell P, Lange R, Scarpignato C. Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge. Therap Adv Gastroenterol 2024; 17:17562848241249664. [PMID: 38887508 PMCID: PMC11181897 DOI: 10.1177/17562848241249664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 04/08/2024] [Indexed: 06/20/2024] Open
Abstract
Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation.
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Affiliation(s)
- Peter Whorwell
- Neurogastroenterology Unit, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK
| | | | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta
- Faculty of Medicine, Chinese University of Hong Kong, Sha Tin, Hong Kong
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4
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Portincasa P, Bonfrate L, Wang DQH, Frühbeck G, Garruti G, Di Ciaula A. Novel insights into the pathogenic impact of diabetes on the gastrointestinal tract. Eur J Clin Invest 2022; 52:e13846. [PMID: 35904418 DOI: 10.1111/eci.13846] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 06/20/2022] [Accepted: 06/26/2022] [Indexed: 11/09/2022]
Abstract
Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Leonilde Bonfrate
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - David Q-H Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, Pamplona, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Gabriella Garruti
- Department of Emergency and Organ Transplants, Unit of Endocrinology, University of Bari Medical School, Bari, Italy
| | - Agostino Di Ciaula
- Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
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Mare R, Sporea I. Gastrointestinal and Liver Complications in Patients with Diabetes Mellitus-A Review of the Literature. J Clin Med 2022; 11:5223. [PMID: 36079153 PMCID: PMC9456591 DOI: 10.3390/jcm11175223] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 08/25/2022] [Accepted: 09/01/2022] [Indexed: 11/29/2022] Open
Abstract
The number of diabetes mellitus patients has increased over the last few years in developing countries, along with obesity and sedentary lifestyle. Besides macroangiopathy and microangiopathy, damage to the nerve fibers of the peripheral nervous system is the most common chronic complication of diabetes. Digestive complications in diabetic patients represent a consequence of diabetic autonomic neuropathy involving the gastrointestinal tract, but unfortunately not always evaluated by diabetologists. Aside from the complications encountered in the digestive tract, patients with diabetes mellitus are prone to developing liver diseases. This review will describe the prevalence of these complications, the modality of diagnosis, and therapeutical solutions in order to reduce the risk of progression of these complications in diabetic subjects.
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Affiliation(s)
- Ruxandra Mare
- Department of Internal Medicine II, Gastroenterology and Hepatology Unit, Advanced Research Center in Gastroenterology and Hepatology “Victor Babes” University of Medicine and Pharmacy, 30041 Timisoara, Romania
- Regional Center of Research in Advanced Hepatology, Academy of Medical Science, 30041 Timisoara, Romania
| | - Ioan Sporea
- Department of Internal Medicine II, Gastroenterology and Hepatology Unit, Advanced Research Center in Gastroenterology and Hepatology “Victor Babes” University of Medicine and Pharmacy, 30041 Timisoara, Romania
- Regional Center of Research in Advanced Hepatology, Academy of Medical Science, 30041 Timisoara, Romania
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Wegeberg AM, Bertoli D, Ejskjaer N, Brock B, Drewes AM, Brock C. Gastrointestinal function in diabetes is affected regardless of asymptomatic appearance. J Intern Med 2022; 291:505-512. [PMID: 34839554 DOI: 10.1111/joim.13416] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Gastrointestinal dysmotility may exist without concomitant symptoms. We hypothesize that asymptomatic individuals with diabetes have altered gastrointestinal function associated with age, cardiac vagal tone and glycaemic control. METHODS One hundred fifty-four asymptomatic participants (61 with type 1 diabetes (T1D), 70 type 2 diabetes (T2D) and 23 healthy volunteers (HV)) underwent wireless motility capsule investigation. Transit times, motility indices and pH were retrieved. Age, cardiac vagal tone, glucose and haemoglobin A1c levels were collected. RESULTS In T1D, prolongation of colonic (p = 0.03) and whole-gut transit times (p = 0.04) were shown. Transpyloric pH rise was decreased in T1D (p = 0.001) and T2D (p = 0.007) and was associated with cardiac vagal tone (p = 0.03) or glucose (p = 0.04) and haemoglobin A1c (p = 0.005). Ileocaecal pH fall was decreased in T2D (p < 0.001). CONCLUSIONS Gastrointestinal function was altered in asymptomatic individuals with diabetes. These findings call for further investigations of gastrointestinal function in order to identify risk factors or even predictors for diabetic enteropathy, particularly when glycaemic control is impaired.
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Affiliation(s)
- Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Davide Bertoli
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Niels Ejskjaer
- Steno Diabetes Center North Denmark, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | | | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.,Steno Diabetes Center North Denmark, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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7
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Sangnes DA, Lundervold K, Bekkelund M, von Volkmann HL, Berentsen B, Gilja OH, Dimcevski G, Søfteland E. Gastrointestinal transit and contractility in diabetic constipation: A wireless motility capsule study on diabetes patients and healthy controls. United European Gastroenterol J 2021; 9:1168-1177. [PMID: 34687494 PMCID: PMC8672085 DOI: 10.1002/ueg2.12169] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 09/29/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Diabetic constipation is traditionally attributed to slow colonic transit, despite limited evidence. More than half of patients find treatment unsatisfactory. To improve treatment, there is a need for better diagnostic understanding of the condition. OBJECTIVE In this wireless motility capsule study, we aimed to investigate gastrointestinal transit and contractility in diabetes patients with and without constipation, and in healthy controls. METHODS We prospectively included type 1 or type 2 diabetes patients with gastrointestinal symptoms. Based on the Gastrointestinal Symptom Rating Scale we distinguished into two groups: with constipation and without constipation. Non-diabetic controls were asymptomatic. All were examined with wireless motility capsule, determining transit times and contractility parameters. RESULTS 57 patients (42 women, 46 with type 1 diabetes) and 26 healthy controls (14 women) were included. We found no difference in transit times between diabetes patients with and without constipation. Compared to healthy controls (35:55, h:min), whole-gut transit was slower in both diabetes patients with constipation (66:15, p = 0.03) and without constipation (71:16, p < 0.001). Small bowel motility index correlated rs = -0.32 (p = 0.01) with constipation symptoms. CONCLUSIONS Diabetes patients with constipation had similar transit times as those without constipation. Both groups had slower whole-gut transit than healthy controls. Constipation was associated with reduced small bowel, but not colonic contractility. Our results imply that other mechanisms than slow colonic transit may be more important in the pathogenesis of diabetic constipation.
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Affiliation(s)
- Dag A. Sangnes
- Department of MedicineHaukeland University HospitalBergenNorway
- Department of Clinical MedicineUniversity of BergenBergenNorway
| | - Katarina Lundervold
- The National Centre for Functional Gastrointestinal DisordersHaukeland University HospitalBergenNorway
- National Centre for Ultrasound in GastroenterologyHaukeland University HospitalBergenNorway
- Department of NeurologyHaukeland University HospitalBergenNorway
| | - Mattis Bekkelund
- The National Centre for Functional Gastrointestinal DisordersHaukeland University HospitalBergenNorway
- Department of Clinical MedicineUniversity of OsloOsloNorway
| | | | - Birgitte Berentsen
- Department of MedicineHaukeland University HospitalBergenNorway
- The National Centre for Functional Gastrointestinal DisordersHaukeland University HospitalBergenNorway
| | - Odd Helge Gilja
- Department of MedicineHaukeland University HospitalBergenNorway
- Department of Clinical MedicineUniversity of BergenBergenNorway
- National Centre for Ultrasound in GastroenterologyHaukeland University HospitalBergenNorway
| | - Georg Dimcevski
- Department of Clinical MedicineUniversity of BergenBergenNorway
- National Centre for Ultrasound in GastroenterologyHaukeland University HospitalBergenNorway
| | - Eirik Søfteland
- Department of MedicineHaukeland University HospitalBergenNorway
- Department of Clinical ScienceUniversity of BergenBergenNorway
- Hormone LaboratoryHaukeland University HospitalBergenNorway
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Protective Effect of Tangshen Formula () on Interstitial Cells of Cajal in Colon of Diabetic Rats. Chin J Integr Med 2021; 28:43-51. [PMID: 34581938 DOI: 10.1007/s11655-021-3297-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/10/2020] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To explore the effect of Tangshen Formula (, TSF), a Chinese herbal medicine, on interstitial cells of Cajal (ICC) in the colon of diabetic rats. METHODS Fifty-four male Wistar rats were randomly divided into normal control (NC, n=14) and high-fat diet (HFD) groups (n=40). After 6 weeks, the rats in the HFD group were injected intraperitoneally streptozotocin once (30 mg/kg). Thirty rats with fasting blood glucose higher than 11.7 mmol/L were randomly divided into diabetes (DM) and TSF groups, 15 rats in each group. Rats in the NC and DM groups were intragastrically administered with saline, and those in the TSF group were given with TSF (2.4 g/kg) once daily for 20 weeks. Expression levels of Bax, Bcl-2, and caspase-3 in colonic smooth muscle layer were measured by Western blotting and immunohistochemical staining. The number of ICC was determined by immunohistochemical staining. Immunofluorescence was used for analyzing the ratio of classically activated macrophages (M1) and alternatively activated macrophages (M2) to total macrophages. Electron microscopy was used to observe the epithelial ultrastructure and junctions. RESULTS TSF appeared to partially prevented loss of ICC in DM rats (P<0.05). Compared with the NC group, expression levels of Bcl-2, Bax, caspase-3, and TNF-α as well as the ratio of M1 to total macrophages increased in DM rats (all P<0.05), and the ratio of M2 to total macrophages decreased (P<0.05 or P<0.01). Compared with the DM group, TSF decreased the expression levels of abovementioned proteins and restore M2 to total macrophages ratio (P<0.05 or P<0.01). TSF appeared to attenuate the ultrastructural changes of epithelia and improve the tight and desmosome junctions between epithelia reduced in the DM rats. CONCLUSION Reduced number of ICC in DM rats may be associated with damage of the intestinal barrier. The protective effects of TSF on ICC may be through repair of the epithelial junctions, which attenuates inflammation and inflammation-initiated apoptosis in colon of DM rats.
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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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10
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Conway RBN, Peltier A, Figaro MK. Constipation and glycemic control. J Diabetes Complications 2021; 35:107799. [PMID: 33303296 DOI: 10.1016/j.jdiacomp.2020.107799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 11/25/2022]
Affiliation(s)
- Rebecca B N Conway
- Department of Community Health, University of Texas Health Science Center at Tyler, Tyler, TX, United States of America.
| | - Amanda Peltier
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
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11
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The Prevalence of Enteropathy Symptoms from the Lower Gastrointestinal Tract and the Evaluation of Anorectal Function in Diabetes Mellitus Patients. J Clin Med 2021; 10:jcm10030415. [PMID: 33499216 PMCID: PMC7866006 DOI: 10.3390/jcm10030415] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 01/16/2021] [Accepted: 01/19/2021] [Indexed: 02/07/2023] Open
Abstract
Complications affecting the gastrointestinal tract often occur in the course of diabetes mellitus (DM). The aim of this study was to evaluate enteropathy symptoms and anorectal function using high-resolution anorectal manometry (HRAM). Fifty DM patients and 20 non-DM controls were enrolled into the study. Clinical data and laboratory tests were collected, physical examination and HRAM were performed. Symptoms in the lower gastrointestinal tract were reported by 72% of patients. DM patients with a long disease duration reported anal region discomfort (p = 0.028) and a sensation of incomplete evacuation (p = 0.036) more often than patients with shorter diabetes duration. Overall, DM patients had a lower maximal squeeze pressure (MSP) (p = 0.001) and a higher mean threshold of minimal rectal sensation (p < 0.01) than control subjects. They presented with enhanced features of dyssynergic defection than the control group. MSP and maximal resting pressure (MRP) were significantly lower in the group of long-term diabetes (p = 0.024; p = 0.026 respectively) than in patients with a short-term diabetes. The same observation was noted for patients with enteropathy symptoms that control for MSP (p < 0.01; p < 0.01; p = 0.03) and MRP (p < 0.001; p = 0.0036; p = 0.0046), respectively, for incontinence, constipation, and diarrhea. Symptoms in the lower gastrointestinal tract are often reported by DM patients. All DM patients have impaired function of the external anal sphincter and present enhanced features of dyssynergic defecation and also impaired visceral sensation. Patients with long-standing DM and patients with enteropathy symptoms have severely impaired function of both anal sphincters.
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12
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Sussman EJ, Singh B, Clegg D, Palmer BF, Kalantar-Zadeh K. Let Them Eat Healthy: Can Emerging Potassium Binders Help Overcome Dietary Potassium Restrictions in Chronic Kidney Disease? J Ren Nutr 2020; 30:475-483. [DOI: 10.1053/j.jrn.2020.01.022] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 11/12/2019] [Accepted: 01/12/2020] [Indexed: 12/29/2022] Open
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Song BK, Kim YS, Kim HS, Oh JW, Lee O, Kim JS. Combined exercise improves gastrointestinal motility in psychiatric in patients. World J Clin Cases 2018; 6:207-213. [PMID: 30148149 PMCID: PMC6107534 DOI: 10.12998/wjcc.v6.i8.207] [Citation(s) in RCA: 5] [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: 03/26/2018] [Revised: 06/11/2018] [Accepted: 06/27/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To examine the effect of combined exercise on colonic transit time (CTT) in admitted psychiatric patients.
METHODS Over a 6-mo period, consecutive in patients with mental illness were recruited from the Somang Hospital Psychiatry Unit. A combined exercise program that included 60 min per day of exercise 3 d per week for 12 wk was performed. Physical fitness and CTT of the patients were measured twice before and twice after the exercise program. CTT was measured using a multiple marker technique with a radio-opaque marker. Changes in the exercising patients’ CTT and weight-, cardiovascular- and fitness-related parameters were statistically assessed.
RESULTS After the 12-wk combined exercise intervention, decreased intestinal transit time was observed in all CTTs of the exercise group, including the right CTT (exercise: 15.6 ± 15.2 vs 9.2 ± 11.9, control: 13.1 ± 10.4 vs 10.9 ± 18.7), left CTT (exercise: 19.7 ± 23.5 vs 10.4 ± 13.2, control: 19.2 ± 19.0 vs 16.9 ± 19.8), recto-sigmoid CTT (exercise: 14.3 ± 16.7 vs 6.7 ± 7.9, control: 15.0 ± 14.4 vs 19.3 ± 30.3), and total colonic transit time (TCTT) (exercise: 50.2 ± 38.1 vs 27.1 ± 28.0, control: 47.4 ± 34.6 vs 47.3 ± 47.3). After the 12-wk combined exercise period, TCTT was significantly shortened in the exercise group compared with that in the control group. In addition to eating habits, water intake, and fiber intake, the increased physical activity level as a result of the 12-wk combined exercise program reduced the CTT.
CONCLUSION The CTT of the psychiatric patients was reduced due to increased physical activity via a 12-wk combined exercise program.
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Affiliation(s)
- Bong Kil Song
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul 151-742, South Korea
| | - Yeon Soo Kim
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul 151-742, South Korea
| | - Hee Soo Kim
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul 151-742, South Korea
- MD, Namyangju Hanyang General Hospital, Namyangju 12048, South Korea
| | - Jung-Woo Oh
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul 151-742, South Korea
| | - On Lee
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul 151-742, South Korea
| | - Joon-Sik Kim
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul 151-742, South Korea
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Lee JM, Paik CN, Kim YJ, Kim DB, Chung WC, Lee KM, Yang JM. The association between a positive lactulose methane breath test and rectocele in constipated patients. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 110:115-122. [PMID: 29271223 DOI: 10.17235/reed.2017.5017/2017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVES Rectocele with constipation might be related to methane (CH4) producing intestinal bacteria. We investigated the breath CH4 levels and the clinical characteristics of colorectal motility in constipated patients with rectocele. METHODS A database of consecutive female outpatients was reviewed for the evaluation of constipation according to the Rome III criteria. The patients underwent the lactulose CH4 breath test (LMBT), colon marker study, anorectal manometry, defecography and bowel symptom questionnaire. The profiles of the lactulose breath test (LBT) in 33 patients with rectocele (with size ≥ 2 cm) and 26 patients with functional constipation (FC) were compared with the breath test results of 30 healthy control subjects. RESULTS The mean size of rectocele was 3.52 ± 1.06 cm. The rate of a positive LMBT (LMBT+) was significantly higher in patients with rectocele (33.3%) than in those with FC (23.1%) or healthy controls (6.7%) (p = 0.04). Breath CH4 concentration was positively correlated with rectosigmoid colon transit time in rectocele patients (γ = 0.481, p < 0.01). A maximum high pressure zone pressure > 155 mmHg was a significant independent factor of LMBT+ in rectocele patients (OR = 8.93, 95% CI = 1.14-71.4, p = 0.04). CONCLUSIONS LMBT+ might be expected in constipated patients with rectocele. Moreover, increased rectosigmoid colonic transit or high anorectal pressure might be associated with CH4 breath levels. Breath CH4 could be an important therapeutic target for managing constipated patients with rectocele.
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Affiliation(s)
- Ji Min Lee
- College of Medicine, St. Vincent's Hospital, The Catholic University of Korea
| | - Chang Nyol Paik
- Internal Medicine, , St. Vincent's Hospital, College of Medicine, Th, South Korea
| | - Yeon Ji Kim
- Division of Gastroenterology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic
| | - Dae Bum Kim
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea
| | - Woo Chul Chung
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Ko
| | - Kang-Moon Lee
- St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Ko
| | - Jin-Mo Yang
- , College of Medicine, St. Vincent's Hospital, The Catholic University of Korea
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Mandolesi D, Frazzoni L, Bazzoli F, Fuccio L. The management of 'hard-to-prepare' colonoscopy patients. Expert Rev Gastroenterol Hepatol 2017; 11:731-740. [PMID: 28594580 DOI: 10.1080/17474124.2017.1338947] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Effective bowel cleansing is crucial for high quality colonoscopy. A notable portion of patients still present with low quality bowel preparation prior to their colonoscopy, compromising the overall quality of their colonoscopy. Areas covered: This review focuses on the main strategies that can improve the cleansing quality with a special interest on those clinical conditions that have been associated with a poor bowel preparation quality, such as patients with chronic constipation, history of bowel resection, liver cirrhosis, diabetes mellitus and chronic kidney disease. The review provides a practical and evidence-based approach to help clinicians in the management of 'hard-to-prepare' patients. Expert commentary: In the past few years, the quality of colonoscopy has become a hot topic and bowel cleansing is a crucial part of it; however, the approach to patients with an increased risk of poor bowel preparation quality is still not always supported by high-quality evidence, since most of these patients are routinely excluded from the clinical studies. Trials focused on this subgroup of patients are recommended to provide tailored bowel preparation regimens and guarantee high-quality procedures.
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Affiliation(s)
- Daniele Mandolesi
- a Gastroenterology Unit, Department of Medical and Surgical Sciences , University of Bologna, S.Orsola-Malpighi Hospital , Bologna , Italy
| | - Leonardo Frazzoni
- a Gastroenterology Unit, Department of Medical and Surgical Sciences , University of Bologna, S.Orsola-Malpighi Hospital , Bologna , Italy
| | - Franco Bazzoli
- a Gastroenterology Unit, Department of Medical and Surgical Sciences , University of Bologna, S.Orsola-Malpighi Hospital , Bologna , Italy
| | - Lorenzo Fuccio
- a Gastroenterology Unit, Department of Medical and Surgical Sciences , University of Bologna, S.Orsola-Malpighi Hospital , Bologna , Italy
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Lee DW, Koo JS, Kang S, Kim SY, Hyun JJ, Jung SW, Yim HJ, Lee SW. Association between bowel habits and quality of bowel preparation for colonoscopy. Medicine (Baltimore) 2017; 96:e7319. [PMID: 28723744 PMCID: PMC5521884 DOI: 10.1097/md.0000000000007319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
The effectiveness of colonoscopy is highly dependent on the quality of bowel preparation. Although many studies have previously evaluated the role of cleansing methods and dosing regimens, few have examined the association between bowel habits and subsequent bowel preparation. Here, we aimed to evaluate the impact of bowel habits on the quality of bowel preparation.A total of 404 patients who underwent a total colonoscopy and completed a personal bowel habit questionnaire at Korea University Hospital between December 2012 and December 2013 were enrolled. The usual stool form of patients was classified into 7 categories according to the Bristol Stool Scale (BSS). The quality of bowel preparation was determined during colonoscopy according to the Ottawa Bowel Preparation Scale (OBPS). Segment scores of ≥3 or total OBPS scores of >7 were defined as poor bowel preparation.Poor bowel preparation was reported in 9.4% of observed colonoscopies. The odds ratio (OR) of poor bowel preparation being associated with infrequent bowel movements (<3/week) was 5.00 (95% confidence interval [CI], 1.91-13.1, P = .001). BSS types 1 and 2 tended to have an association with poor bowel preparation, but the association was statistically insignificant (OR: 2.38; 95% CI, 0.90-6.33, P = .082). After adjusting for age, sex, drinking, presence of diabetes mellitus, and bowel preparation regimen, infrequent bowel movement (<3/week) was still significantly associated with poor bowel preparation. When subdividing by colonic segment, it was significantly associated with poor bowel preparation in all segments.Infrequent bowel movement (<3/week) was significantly associated with poor bowel preparation.
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Zhao M, Liao D, Zhao J. Diabetes-induced mechanophysiological changes in the small intestine and colon. World J Diabetes 2017; 8:249-269. [PMID: 28694926 PMCID: PMC5483424 DOI: 10.4239/wjd.v8.i6.249] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/05/2017] [Accepted: 05/05/2017] [Indexed: 02/05/2023] Open
Abstract
The disorders of gastrointestinal (GI) tract including intestine and colon are common in the patients with diabetes mellitus (DM). DM induced intestinal and colonic structural and biomechanical remodeling in animals and humans. The remodeling is closely related to motor-sensory abnormalities of the intestine and colon which are associated with the symptoms frequently encountered in patients with DM such as diarrhea and constipation. In this review, firstly we review DM-induced histomorphological and biomechanical remodeling of intestine and colon. Secondly we review motor-sensory dysfunction and how they relate to intestinal and colonic abnormalities. Finally the clinical consequences of DM-induced changes in the intestine and colon including diarrhea, constipation, gut microbiota change and colon cancer are discussed. The final goal is to increase the understanding of DM-induced changes in the gut and the subsequent clinical consequences in order to provide the clinicians with a better understanding of the GI disorders in diabetic patients and facilitates treatments tailored to these patients.
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Tangshen Formula Attenuates Colonic Structure Remodeling in Type 2 Diabetic Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:4064156. [PMID: 28303157 PMCID: PMC5338308 DOI: 10.1155/2017/4064156] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 12/26/2016] [Indexed: 12/20/2022]
Abstract
Aim. This study investigated the effect and mechanism of the Chinese herbal medicine Tangshen Formula (TSF) on GI structure remodeling in the rat model of diabetes. Methods. Type 2 diabetic rats were used. Wet weight per unit length, layer thicknesses, levels of collagens I and III, nuclear factor kappa B (NF-κB), interferon-γ (IFN-γ), interleukin-6 (IL-6), transforming growth factor-β1 (TGF-β1), and Smad2/3 expression in the rat colon were measured. Results. Compared with the control group animals, wet weight and layer thicknesses of the colon increased, and expressions of collagens I and III, NF-κB, IFN-γ, IL-6, TGF-β1, and Smad2/3 increased significantly in the diabetic animals. TSF inhibited increase in colonic wet weight and layer thicknesses, downregulated expressions of collagens I and III in the mucosal layer, and downregulated expressions of NF-κB, IFN-γ, IL-6, TGF-β1, and Smad2/3 in the colon wall. Furthermore, level of expression of NF-κB was associated with those of TGF-β1 and Smad2/3. Expression of TGF-β1 was associated with the most histomorphometric parameters including colonic weight, mucosal and muscle thicknesses, and levels of collagens I and III in mucosal layer. Conclusion. TSF appears to attenuate colonic structure remodeling in type 2 diabetic rats through inhibiting the overactivated pathway of NF-κB, thus reducing expressions of TGF-β1.
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Abstract
Physical activity is associated with a reduced risk of colorectal cancer. We examined the colon transit time (CTT) according to the total energy expenditure (TEE) in psychiatry unit patients. The study participants included 67 adults, with a mean age of 49.8 years. The participants used an accelerometer for 7 days to measure their 1-week TEE. They took a capsule containing 20 radio-opaque markers for 3 days. On the 4th day and 7th day, a supine abdominal radiography was performed. According to the TEE of all study participants, the upper 30%, middle 30%, and lower 40% were classified into groups according to high (H), moderate (M), and low (L) physical activity. The mean total CTT was 52.0 hours. The segmental CTT for the right, left, and recto-sigmoid colon were 15.3 hours, 19.2 hours, and 17.4 hours. Total CTT in the H group was significantly shorter than that in the L group (p = .010). A comparison of the segmental CTT between the L, M, and H groups showed that the right CTT (p = .010) of the H group was significantly shorter than that of the M group. The left CTT of the M group (p = .028) and H group (p = .004) was significantly shorter than that of the L group. The recto-sigmoid CTT (p = .016) of the M group was significantly shorter than that of the L group. The study showed that moderate and high TEE was assisted with reduced CTT.
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Schmid D, Behrens G, Matthews CE, Leitzmann MF. Physical Activity and Risk of Colon Cancer in Diabetic and Nondiabetic US Adults. Mayo Clin Proc 2016; 91:1693-1705. [PMID: 27916155 PMCID: PMC8575013 DOI: 10.1016/j.mayocp.2016.08.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 08/05/2016] [Accepted: 08/08/2016] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To determine whether moderate to vigorous physical activity is associated with a decreased risk of colon cancer in diabetic patients. PATIENTS AND METHODS We evaluated the association between physical activity and colon cancer in 25,753 patients with a self-reported history of diabetes and in 274,965 nondiabetic individuals from the National Institutes of Health-AARP Diet and Health Study who were aged 50 to 71 years in 1995-1996. Moderate to vigorous physical activity was assessed at baseline using a self-administered questionnaire. Follow-up for colon cancer incidence extended to December 31, 2011. RESULTS During 13.0 years of follow-up, 480 diabetic patients and 4151 nondiabetic individuals had development of colon cancer. Among diabetic patients, compared with never/rarely engaging in physical activity, more than 7 h/wk of physical activity exhibited a reduced risk of colon cancer in the age- and sex-adjusted model (hazard ratio [HR], 0.74; 95% CI, 0.56-0.996; P=.16 for trend). This association was attenuated and no longer statistically significant after additional control for other covariates (HR, 0.78; 95% CI, 0.58-1.05; P=.29 for trend). By comparison, physical activity was inversely related to colon cancer risk in nondiabetic individuals (multivariate-adjusted HR, 0.81; 95% CI, 0.73-0.89; P<.001 for trend). CONCLUSION In this investigation of the relationship between physical activity and colon cancer in diabetic patients, we found a statistically significant inverse relationship in the age- and sex-adjusted model, which was no longer statistically significant in the multivariate-adjusted model. A reduced risk was noted among nondiabetic individuals, irrespective of other covariates. Future studies with a larger number of participants are required to explore whether physical activity beneficially affects colon cancer risk among diabetic patients.
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Affiliation(s)
- Daniela Schmid
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
| | - Gundula Behrens
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
| | - Charles E Matthews
- Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute, Bethesda, MD
| | - Michael F Leitzmann
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany
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Abstract
Gastrointestinal symptoms occur frequently among people with diabetes mellitus and are associated with considerable morbidity. Enteropathy, or large bowel dysfunction, includes constipation, diarrhea and fecal incontinence, and is particularly disturbing for many patients. The pathogenesis of diabetic enteropathy is complex, primarily related to gastrointestinal autonomic dysfunction and etiologically associated with chronic hyperglycemia and diabetes duration. Since there are many other non-iatrogenic and iatrogenic causes of the cardinal symptoms of large bowel dysfunction, patients suspected of having diabetic enteropathy require detailed evaluation. The management of patients with diabetic enteropathy is challenging, and often requires a multidisciplinary approach focusing on a combination of symptom mitigation and glycemic control.
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22
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Izzy M, Changela K, Alhankawi D, Haeri NS, Shah S, Jibara G, Anand S, Singhal S. Impact of glycemic control on colonoscopy outcomes: bowel preparation and polyp detection. Ann Gastroenterol 2016; 29:332-5. [PMID: 27366034 PMCID: PMC4923819 DOI: 10.20524/aog.2016.0060] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 02/10/2016] [Indexed: 12/12/2022] Open
Abstract
Background The negative effect of diabetes mellitus (DM) on the colonoscopy preparation has been previously established. Metabolic syndrome has been shown to increase risk for malignancy and possibly for premalignant lesions. This study aimed to investigate the impact of DM control on colonoscopy outcomes including bowel preparation and adenoma detection rate (ADR). Methods We included patients with DM who underwent colonoscopy in our hospital and had a documented glycated hemoglobin (HbA1C) within 3 months. Patients were categorized into three groups based on their HbA1C level. The clinical and endoscopic data were collected and analyzed. Results Our cohort included 352 DM patients. The mean age was 63.5 years. When patients were analyzed based on HBA1C, bowel preparation was poor in 46.7% of patients with good glycemic control, 52.1% of patients with fair control and 50% of patients with poor control. ADR was 24.3% in patients with good glycemic control, 20.2% in patients with fair glycemic control and 27.1% in patients with poor glycemic control. There was no statistically significant difference in the quality of preparation or adenoma detection amongst the groups. Conclusion The degree of glycemic control did not impact the quality of bowel preparation or ADR.
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Affiliation(s)
- Manhal Izzy
- Division of Gastroenterology and Hepatology, Montefiore Medical Center, Bronx, NY (Manhal Izzy); Division of Gastroenterology, The Brooklyn Hospital Center, Brooklyn, NY (Manhal Izzy, Kinesh Changela, Dhuha Alhankawi, Nami Safai Haeri, Sury Anand)
| | - Kinesh Changela
- Division of Gastroenterology, The Brooklyn Hospital Center, Brooklyn, NY (Manhal Izzy, Kinesh Changela, Dhuha Alhankawi, Nami Safai Haeri, Sury Anand)
| | - Dhuha Alhankawi
- Division of Gastroenterology, The Brooklyn Hospital Center, Brooklyn, NY (Manhal Izzy, Kinesh Changela, Dhuha Alhankawi, Nami Safai Haeri, Sury Anand)
| | - Nami Safai Haeri
- Division of Gastroenterology, The Brooklyn Hospital Center, Brooklyn, NY (Manhal Izzy, Kinesh Changela, Dhuha Alhankawi, Nami Safai Haeri, Sury Anand)
| | - Sulay Shah
- Hospitalist Program, Atlanticare Regional Medical Center, Atlantic City, NJ (Sulay Shah)
| | - Ghalib Jibara
- Urology, The Brookdale University Hospital and Medical Center, Brooklyn, NY (Ghalib Jibara)
| | - Sury Anand
- Division of Gastroenterology, The Brooklyn Hospital Center, Brooklyn, NY (Manhal Izzy, Kinesh Changela, Dhuha Alhankawi, Nami Safai Haeri, Sury Anand)
| | - Shashideep Singhal
- University of Texas Health Science Center at Houston (Shashideep Singhal), USA
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Kamiński JP, Pai A, Ailabouni L, Park JJ, Marecik SJ, Prasad LM, Abcarian H. Role of epidural and patient-controlled analgesia in site-specific laparoscopic colorectal surgery. JSLS 2016; 18:JSLS.2014.00207. [PMID: 25419110 PMCID: PMC4234047 DOI: 10.4293/jsls.2014.00207] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background and Objectives: Limited data are available comparing epidural and patient-controlled analgesia in site-specific colorectal surgery. The aim of this study was to evaluate 2 modes of analgesia in patients undergoing laparoscopic right colectomy (RC) and low anterior resection (LAR). Methods: Prospectively collected data on 433 patients undergoing laparoscopic or laparoscopic-assisted colon surgery at a single institution were retrospectively reviewed from March 2004 to February 2009. Patients were divided into groups undergoing RC (n = 175) and LAR (n = 258). These groups were evaluated by use of analgesia: epidural analgesia, “patient-controlled analgesia” alone, and a combination of both. Demographic and perioperative outcomes were compared. Results: Epidural analgesia was associated with a faster return of bowel function, by 1 day (P < .001), in patients who underwent LAR but not in the RC group. Delayed return of bowel function was associated with increased operative time in the LAR group (P = .05), patients with diabetes who underwent RC (P = .037), and patients after RC with combined analgesia (P = .011). Mean visual analogue scale pain scores were significantly lower with epidural analgesia compared with patient-controlled analgesia in both LAR and RC groups (P < .001). Conclusion: Epidural analgesia was associated with a faster return of bowel function in the laparoscopic LAR group but not the RC group. Epidural analgesia was superior to patient-controlled analgesia in controlling postoperative pain but was inadequate in 28% of patients and needed the addition of patient-controlled analgesia.
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Affiliation(s)
- Jan P Kamiński
- Department of Surgery, University of Illinois Metropolitan Group Hospitals, Chicago, Illinois
| | - Ajit Pai
- Division of Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, Illinois
| | - Luay Ailabouni
- Division of Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, Illinois
| | - John J Park
- Division of Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, Illinois
| | - Slawomir J Marecik
- Division of Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, Illinois
| | - Leela M Prasad
- Division of Colon and Rectal Surgery, Advocate Lutheran General Hospital, Park Ridge, Illinois
| | - Herand Abcarian
- Division of Colon and Rectal Surgery, John H. Stroger Hospital of Cook County, Chicago, Illinois
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Antunes NDJ, Cavalli RC, Marques MP, Moisés ECD, Lanchote VL. Influence of gestational diabetes on the stereoselective pharmacokinetics and placental distribution of metoprolol and its metabolites in parturients. Br J Clin Pharmacol 2015; 79:605-16. [PMID: 25291152 DOI: 10.1111/bcp.12523] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Accepted: 09/19/2014] [Indexed: 12/26/2022] Open
Abstract
AIM To investigate the influence of gestational diabetes mellitus (GDM) on the kinetic disposition and transplacental and amniotic fluid distribution of metoprolol and its metabolites O-desmethylmetoproloic acid and α-hydroxymetoprolol stereoisomers in hypertensive parturients receiving a single dose of the racemic drug. METHODS The study was conducted on hypertensive parturients with well-controlled GDM (n = 11) and non-diabetic hypertensive parturients (n = 24), all receiving a single 100 mg oral dose of racemic metoprolol tartrate before delivery. Serial maternal blood samples (0-24 h) and umbilical blood and amniotic fluid samples were collected for the quantitation of metoprolol and its metabolite stereoisomers using LC-MS/MS or fluorescence detection. RESULTS The kinetic disposition of metoprolol and its metabolites was stereoselective in the diabetic and control groups. Well-controlled GDM prolonged tmax for both enantiomers of metoprolol (1.5 vs. 2.5 h R-(+)-MET; 1.5 vs. 2.75 h S-(-)-MET) and O-desmethylmetoproloic acid (2.0 vs. 3.5 h R-(+)-AOMD; 2.0 vs. 3.0 h S-(-)-OAMD), and for the four stereoisomers of α-hydroxymetoprolol (2.0 vs. 3.0 h for 1'S,2R-, 1'R,2R- and 1'R,2S-OHM; 2.0 vs. 3.5 h for 1'S,2S-OHM) and reduced the transplacental distribution of 1'S,2S-, 1'R,2R-, and 1'R,2S-OHM by approximately 20%. CONCLUSIONS The kinetic disposition of metoprolol was enantioselective, with plasma accumulation of the S-(-)-MET eutomer. Well-controlled GDM prolonged the tmax of metoprolol and O-desmethylmetoproloic acid enantiomers and the α-hydroxymetoprolol stereoisomers and reduced by about 20% the transplacental distribution of 1'S,2S-, 1'R,2R-, and 1'R,2S-OHM. Thus, well-controlled GDM did not change the activity of CYP2D6 and CYP3A involved in metoprolol metabolism.
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Affiliation(s)
- Natalícia de Jesus Antunes
- Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil
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Horváth VJ, Putz Z, Izbéki F, Körei AE, Gerő L, Lengyel C, Kempler P, Várkonyi T. Diabetes-related dysfunction of the small intestine and the colon: focus on motility. Curr Diab Rep 2015; 15:94. [PMID: 26374571 DOI: 10.1007/s11892-015-0672-8] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In contrast to gastric dysfunction, diabetes-related functional impairments of the small and large intestine have been studied less intensively. The gastrointestinal tract accomplishes several functions, such as mixing and propulsion of luminal content, absorption and secretion of ions, water, and nutrients, defense against pathogens, and elimination of waste products. Diverse functions of the gut are regulated by complex interactions among its functional elements, including gut microbiota. The network-forming tissues, the enteric nervous system) and the interstitial cells of Cajal, are definitely impaired in diabetic patients, and their loss of function is closely related to the symptoms in diabetes, but changes of other elements could also play a role in the development of diabetes mellitus-related motility disorders. The development of our understanding over the recent years of the diabetes-induced dysfunctions in the small and large intestine are reviewed in this article.
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Affiliation(s)
- Viktor József Horváth
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary.
| | - Zsuzsanna Putz
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - Ferenc Izbéki
- Fejér Megyei Szent György Egyetemi Oktató Kórház, Székesfehérvár, Hungary
| | - Anna Erzsébet Körei
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - László Gerő
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - Csaba Lengyel
- 1st Department of Medicine, University of Szeged, Szeged, Hungary
| | - Péter Kempler
- 1st Department of Medicine, Semmelweis University, Korányi Sándor utca 2/a, 1083, Budapest, Hungary
| | - Tamás Várkonyi
- 1st Department of Medicine, University of Szeged, Szeged, Hungary
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Coleski R, Wilding GE, Semler JR, Hasler WL. Blunting of Colon Contractions in Diabetics with Gastroparesis Quantified by Wireless Motility Capsule Methods. PLoS One 2015; 10:e0141183. [PMID: 26510137 PMCID: PMC4624915 DOI: 10.1371/journal.pone.0141183] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2015] [Accepted: 10/06/2015] [Indexed: 12/12/2022] Open
Abstract
Generalized gut transit abnormalities are observed in some diabetics with gastroparesis. Relations of gastric emptying abnormalities to colon contractile dysfunction are poorly characterized. We measured colon transit and contractility using wireless motility capsules (WMC) in 41 healthy subjects, 12 diabetics with gastroparesis (defined by gastric retention >5 hours), and 8 diabetics with normal gastric emptying (≤5 hours). Overall numbers of colon contractions >25 mmHg were calculated in all subjects and were correlated with gastric emptying times for diabetics with gastroparesis. Colon transit periods were divided into quartiles by time and contraction numbers were calculated for each quartile to estimate regional colon contractility. Colon transit in diabetics with gastroparesis was prolonged vs. healthy subjects (P<0.0001). Overall numbers of colon contractions in gastroparetics were lower than controls (P = 0.02). Diabetics with normal emptying showed transit and contraction numbers similar to controls. Gastric emptying inversely correlated with overall contraction numbers in gastroparetics (r = -0.49). Numbers of contractions increased from the 1st to 4th colon transit quartile in controls and diabetics with normal emptying (P≤0.04), but not gastroparetics. Numbers of contractions in the 3rd and 4th quartiles were reduced in gastroparetics vs. healthy controls (P≤0.05) and in the 4th quartile vs. diabetics with normal emptying (P = 0.02). Numbers of contractions were greatest in the final 15 minutes of transit, but were reduced in gastroparetics vs. healthy controls and diabetics with normal emptying (P≤0.005). On multivariate analyses, differences in numbers of contractions were not explained by demographic or clinical variables. In conclusion, diabetics with gastroparesis exhibit delayed colon transit associated with reductions in contractions that are prominently blunted in latter transit phases and which correlate with delayed gastric emptying, while diabetics with normal emptying show no significant colonic impairments. These findings emphasize diabetic gastroparesis may be part of a generalized dysmotility syndrome.
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Affiliation(s)
- Radoslav Coleski
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, United States of America
| | - Gregory E. Wilding
- Department of Biostatistics, State University of New York at Buffalo, Buffalo, New York, United States of America
| | - John R. Semler
- Medtronic, Sunnyvale, California, United States of America
| | - William L. Hasler
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, Ann Arbor, Michigan, United States of America
- * E-mail:
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Yang J, Yuan WQ, Lu CQ, Chen J. Incidence and risk factors for constipation in patients with acute myocardial infarction. Shijie Huaren Xiaohua Zazhi 2015; 23:4442-4446. [DOI: 10.11569/wcjd.v23.i27.4442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the incidence and risk factors for constipation in patients with acute myocardial infarction (AMI).
METHODS: The study had a retrospective design, and 334 AMI patients were included. The incidence and risk factors for constipation were analyzed in these patients.
RESULTS: The incidence of constipation was 32.6% in the overall AMI patient population, 61.5% in those who did not use laxatives, 21.9% in those who received milk fructose, and 24.8% in those who received rhubarb soda. The use of laxatives was a protective factor for constipation during the hospitalization period (OR = 0.544, P < 0.05), while combined diabetes (OR = 1.813, P < 0.05) and the improper timing of laxative use were risk factors (OR = 0.589, P < 0.05).
CONCLUSION: The incidence of constipation in AMI patients is high, and there are many influencing factors. Preventive measures should be taken to reduce the occurrence of constipation in hospitalized AMI patients.
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Li J, Guo HF, Liu C, Zhong Z, Liu L, Liu XD. Prediction of drug disposition in diabetic patients by means of a physiologically based pharmacokinetic model. Clin Pharmacokinet 2015; 54:179-93. [PMID: 25316573 DOI: 10.1007/s40262-014-0192-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND OBJECTIVE Accumulating evidence has shown that diabetes mellitus may affect the pharmacokinetics of some drugs, leading to alteration of pharmacodynamics and/or toxic effects. The aim of this study was to develop a novel physiologically based pharmacokinetic (PBPK) model for predicting drug pharmacokinetics in patients with type 2 diabetes mellitus quantitatively. METHODS Contributions of diabetes-induced alteration of physiological parameters including gastric emptying rates, intestinal transit time, drug metabolism in liver and kidney functions were incorporated into the model. Plasma concentration-time profiles and pharmacokinetic parameters of seven drugs (antipyrine, nisoldipine, repaglinide, glibenclamide, glimepiride, chlorzoxazone, and metformin) in non-diabetic and diabetic patients were predicted using the developed model. The PBPK model coupled with a Monte-Carlo simulation was also used to predict the means and variability of pharmacokinetic parameters. RESULTS The predicted area under the plasma concentration-time curve (AUC) and maximum (peak) concentration (C max) were reasonably consistent (<2-fold errors) with the reported values. Sensitivity analysis showed that gut transit time, hepatic enzyme activity, and renal function affected the pharmacokinetic characteristics of these drugs. Shortened gut transit time only decreased the AUC of controlled-released drugs and drugs with low absorption rates. Impairment of renal function markedly altered pharmacokinetics of drugs mainly eliminated via the kidneys. CONCLUSION All of these results indicate that the developed PBPK model can quantitatively predict pharmacokinetic alterations induced by diabetes.
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Affiliation(s)
- Jia Li
- Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, 210009, China
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Breath methane positivity is more common and higher in patients with objectively proven delayed transit constipation. Eur J Gastroenterol Hepatol 2013; 25:726-32. [PMID: 23395994 DOI: 10.1097/meg.0b013e32835eb916] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Methane (CH4)-producing intestinal bacteria might be related to constipation. This study was carried out to evaluate the association between breath CH4, colonic transit, and anorectal pressure in constipated patients. METHODS A database of consecutive 62 constipated patients fulfilling the Rome III with the lactulose CH4 breath test (LMBT), a colon marker study, and anorectal manometry was studied. The profile of LMBT in patients was compared with 49 healthy controls. The positivity to LMBT (LMBT+) was defined as CH4 of at least 10 ppm in baseline or above baseline within 90 min. There were two types of constipation: normal and delayed transit. RESULTS There were significant differences in the breath CH4 between patients with delayed transit and (a) normal transit from 0 to 135 min or (b) healthy controls from 0 to 180 min. The LMBT+ was higher in delayed transit patients than in healthy controls (58.8 vs.12.2%) or in normal transit patients (vs. 13.3%), respectively (P<0.01). The delayed transit was the only independent factor for LMBT+ [odds ratio (95% confidence interval), 27.8 (3.32-250.00), P<0.01]. The left and total colonic transit time were significantly increased in LMBT-positive than in LMBT-negative patients. Significant correlations were found between total CH4 and the time of left or total colonic transit. However, no difference was found in the parameters of manometry by LMBT status. CONCLUSION A positive breath CH4 was associated with delayed colonic transit and left colon, and it could be a new therapeutic target for the management of constipated patients with delayed colonic transit.
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In vivo characterization of intestinal effects of endomorphin-1 and endomorphin-2 in type 1 diabetic mice. Eur J Pharmacol 2013; 698:499-504. [DOI: 10.1016/j.ejphar.2012.10.044] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2012] [Revised: 10/27/2012] [Accepted: 10/31/2012] [Indexed: 11/21/2022]
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Dostalek M, Akhlaghi F, Puzanovova M. Effect of Diabetes Mellitus on Pharmacokinetic and Pharmacodynamic Properties of Drugs. Clin Pharmacokinet 2012. [DOI: 10.1007/bf03261926] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Dostalek M, Akhlaghi F, Puzanovova M. Effect of diabetes mellitus on pharmacokinetic and pharmacodynamic properties of drugs. Clin Pharmacokinet 2012; 51:481-99. [PMID: 22668340 DOI: 10.2165/11631900-000000000-00000] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The effects of diabetes mellitus on the pharmacokinetics and pharmacodynamics of drugs have been well described in experimental animal models; however, only minimal data exist for humans and the current knowledge regarding the effects of diabetes on these properties remains unclear. Nevertheless, it has been observed that the pharmacokinetics and pharmacodynamics of drugs are changed in subjects with diabetes. It has been reported that diabetes may affect the pharmacokinetics of various drugs by affecting (i) absorption, due to changes in subcutaneous adipose blood flow, muscle blood flow and gastric emptying; (ii) distribution, due to non-enzymatic glycation of albumin; (iii) biotransformation, due to regulation of enzymes/transporters involved in drug biotransformation; and (iv) excretion, due to nephropathy. Previously published data also suggest that diabetes-mediated changes in the pharmacokinetics of a particular drug cannot be translated to others. Although clinical studies exploring the effect of diabetes on pharmacodynamics are still very limited, there is evidence that disease-mediated effects are not limited only to pharmacokinetics but also alter pharmacodynamics. However, for many drugs it remains unclear whether these influences reflect diabetes-mediated changes in pharmacokinetics rather than pharmacodynamics. In addition, even though diabetes-mediated pharmacokinetics and pharmacodynamics might be anticipated, it is important to study the effect on each drug and not generalize from observed data. The available data indicate that there is a significant variability in drug response in diabetic subjects. The discrepancies between individual clinical studies as well as between ex vivo and clinical studies are probably due to (i) the restricted and focused population of subjects in clinical studies; (ii) failure to consider type, severity and duration of the disease; (iii) histopathological characteristics generally being missing; and (iv) other factors such as varying medication use, dietary protein intake, age, sex and obesity. The obesity epidemic in the developed world has also inadvertently influenced the directions of pharmacological research. This review attempts to map new information gained since Gwilt published his paper in Clinical Pharmacokinetics in 1991. Although a large body of research has been conducted and significant progress has been made, we still have to conclude that the available information regarding the effect of diabetes on pharmacokinetics and pharmacodynamics remains unclear and further clinical studies are required before we can understand the clinical significance of the effect. An understanding of diabetes-mediated changes as well as of the source of the variability should lead to the improvement of the medical management and clinical outcomes in patients with this widespread disease.
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Affiliation(s)
- Miroslav Dostalek
- Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA
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Gatopoulou A, Papanas N, Maltezos E. Diabetic gastrointestinal autonomic neuropathy: current status and new achievements for everyday clinical practice. Eur J Intern Med 2012; 23:499-505. [PMID: 22863425 DOI: 10.1016/j.ejim.2012.03.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Revised: 02/27/2012] [Accepted: 03/01/2012] [Indexed: 12/14/2022]
Abstract
Gastrointestinal symptoms occur frequently among patients with diabetes mellitus and are associated with considerable morbidity. Diabetic gastrointestinal autonomic neuropathy represents a complex disorder with multifactorial pathogenesis, which is still not well understood. It appears to involve a spectrum of metabolic and cellular changes that affect gastrointestinal motor and sensory control. It may affect any organ in the digestive system. Clinical manifestations are often underestimated, and therefore autonomic neuropathy should be suspected in all diabetic patients with unexplained gastrointestinal symptoms. Advances in technology have now enabled assessment of gastrointestinal motor function. Moreover, novel pharmacological approaches, along with endoscopic and surgical treatment options, contribute to improved outcomes. This review summarises the progress achieved in diabetic gastrointestinal autonomic neuropathy during the last years, focusing on clinical issues of practical importance to the everyday clinician.
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Affiliation(s)
- A Gatopoulou
- Second Department of Internal Medicine, Democritus University of Thrace, Greece.
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Song BK, Cho KO, Jo Y, Oh JW, Kim YS. Colon transit time according to physical activity level in adults. J Neurogastroenterol Motil 2012; 18:64-9. [PMID: 22323989 PMCID: PMC3271256 DOI: 10.5056/jnm.2012.18.1.64] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2011] [Revised: 12/19/2011] [Accepted: 12/22/2011] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND/AIMS Physical activity (PA) is associated with a reduced risk of colorectal cancer. Thus, we examined the colon transit time (CTT) according to the physical activity level (PAL) in Korean adults. METHODS The study subjects were 49 adults: 24 males and 25 females. The subjects used an accelerometer for 7 consecutive days to measure the 1-week PAL. The subjects took a capsule containing 20 radio-opaque markers for 3 days. On the fourth day, a supine abdominal radiography was performed. According to the total activity count of all study subjects, the upper 25%, middle 50% and lower 25% were classified into the high (H), moderate (M) and low (L) physical activity (PA) groups, respectively. RESULTS The total CTT was significantly longer in the female (25.8 hours) than in the male subjects (7.4 hours) (P = 0.002). In regard to difference on PAL, although there was no significant difference among the male subjects, the right CTT in the female subjects was significantly shorter in H group than in M group (P = 0.048), and the recto-sigmoid CTT was significantly shorter in H group than in L group (P = 0.023). Furthermore, there were significant differences in total CTT between L and M groups (P = 0.022), M and H groups (P = 0.026) and between L and H groups (P = 0.002). CONCLUSIONS The female, but not male, subjects showed that moderate and high PAL assisted colon transit.
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Affiliation(s)
- Bong Kil Song
- Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, Seoul, Korea
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Pehl C. Sekundäre Form der Obstipation aufgrund von medikamentösen Nebenwirkungen und endokrinen, neurologischen und psychiatrischen Erkrankungen medikamentös-konservative Therapieoptionen. VISZERALMEDIZIN 2012. [DOI: 10.1159/000341720] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Domènech A, Pasquinelli G, De Giorgio R, Gori A, Bosch F, Pumarola M, Jiménez M. Morphofunctional changes underlying intestinal dysmotility in diabetic RIP-I/hIFNβ transgenic mice. Int J Exp Pathol 2011; 92:400-12. [PMID: 22050417 DOI: 10.1111/j.1365-2613.2011.00789.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role. The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I/hIFNβ transgenic mice treated with multiple very low doses of streptozotocin (20 mg/kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model.
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Affiliation(s)
- Anna Domènech
- Department of Animal Medicine and Surgery, Universitat Autònoma de Barcelona, Bellaterra, Spain.
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Myung SJ, Lee TH, Huh KC, Choi SC, Sohn CI. [Diagnosis of constipation: a systematic review]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2010; 55:316-24. [PMID: 20697191 DOI: 10.4166/kjg.2010.55.5.316] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
To diagnose constipation accurately in self-reported constipated patients is very important not to miss organic disease and prevent therapeutic abuse. To investigate the etiology of functional constipation is also important to determine the therapeutic modality of constipation. In this systemic review, the clinical usefulness of symptom evaluation, diagnostic tests to rule out organic and systemic disease, and functional tests to discriminate underlying pathophysiology in the diagnosis of constipation were discussed. No specific symptoms or tests were available to predict organic versus functional constipation or differentiate slow transit constipation versus evacuation disorder. Therefore, collaborative studies are necessary to determine the pathophysiology of this disorder.
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Affiliation(s)
- Seung-Jae Myung
- Department of Medicine, Sungkyunkwan University, School of Medicine, Seoul, Korea
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Eldesoky A, Bahgat M, El-Shreif M, El-Gamal S, Taha K. Anorectal dysfunctions in diabetic autonomic neuropathy and microangiopathy. Arab J Gastroenterol 2010. [DOI: 10.1016/j.ajg.2010.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Zheng Q, Qiu WC, Yan J, Wang WG, Yu S, Wang ZG, Ai KX. Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice. World J Gastroenterol 2008; 14:4795-9. [PMID: 18720542 PMCID: PMC2739343 DOI: 10.3748/wjg.14.4795] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice.
METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice and diabetic mice treated with GHRP-6 at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of GHRP-6. Based on the most effective GHRP-6 dosage, atropine was given at 1 mg/kg for 15 min before the GHRP-6 injection for each measurement. The mice in each group were sacrificed 20 min later and the percentages of GE, IT, and CT were calculated.
RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT. The most effective dose of GHRP-6 was 200 μg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT.
CONCLUSION: GHRP-6 accelerates delayed GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore, has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
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Qiu WC, Wang ZG, Lv R, Wang WG, Han XD, Yan J, Wang Y, Zheng Q, Ai KX. Ghrelin improves delayed gastrointestinal transit in alloxan-induced diabetic mice. World J Gastroenterol 2008; 14:2572-7. [PMID: 18442208 PMCID: PMC2708372 DOI: 10.3748/wjg.14.2572] [Citation(s) in RCA: 30] [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] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of ghrelin on delayed gastrointestinal transit in alloxan-induced diabetic mice.
METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice group and diabetic mice group treated with ghrelin at doses of 0, 20, 50, 100 and 200 &mgr;g/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of ghrelin. Based on the most effective ghrelin dosage, atropine was given at 1 mg/kg 15 min before the ghrelin injection for each measurement. The mice in each group were sacrificed 20 min later and their stomachs, intestines, and colons were harvested immediately. The amount of phenol red was measured. Percentages of GE, IT, and CT were calculated.
RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice (22.9 ± 1.4 vs 28.1 ± 1.3, 33.5 ± 1.2 vs 43.2 ± 1.9, 29.5 ± 1.9 vs 36.3 ± 1.6, P < 0.05). In the diabetic mice, ghrelin improved both GE and IT, but not CT. The most effective dose of ghrelin was 100 &mgr;g/kg and atropine blocked the prokinetic effects of ghrelin on GE and IT.
CONCLUSION: Ghrelin accelerates delayed GE and IT but has no effect on CT in diabetic mice. Ghrelin may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.
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Southwell BR. Loss of interstitial cells of Cajal may be central to poor intestinal motility in diabetes mellitus. J Gastroenterol Hepatol 2008; 23:505-7. [PMID: 18397479 DOI: 10.1111/j.1440-1746.2008.05363.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Wu GJ, Lin L, Zhang HJ, Li XL, Luo Y, Wang MF. Effect of interference in heme oxygenase on colonic dysfunction of diabetic rats. Shijie Huaren Xiaohua Zazhi 2007; 15:14-21. [DOI: 10.11569/wcjd.v15.i1.14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of heme oxygenase (HO) interference on the colonic dysfunction in rats with diabetes mellitus (DM).
METHODS: DM model was established by intraperitoneal injection of streptozotocin (STZ) in Sprague and Dawley rats. Six weeks later, the diabetic rats were validated to be suffered with gastrointestinal dysfunction using charcoal (Indian ink) propulsion experiment. Then the rest rats were randomly divided into 4 groups, named group A (normal control), B (diabetic rats without interference), C (diabetic rats administrated with Hemin, the inducer of HO) and D [diabetic rats administrated with zinc protoporphyrin Ⅸ (ZnPP Ⅸ), the inhibitor of HO]. The weight and blood glucose of the rats were tested. Three more weeks later, the motilities of the strips isolated from the proximal and distal colon were recorded. The level of HO in the colon was also detected by immunohistochemistry and Western blot.
RESULTS: The model of diabetic rats suffered with gastrointestinal dysfunction was successfully duplicated. Administration of Hemin or ZnPP Ⅸ had no effect on the weight or blood glucose of diabetic rats (P > 0.05). There was no significant difference in HO-2 expression of the distal colon between the diabetic rats with or/and without interference (P > 0.05). But in comparison with the controls, HO-2 expression of the proximal colon in group B, C or D was significantly declined (Western blot: 1.20 ± 0.09, 1.08 ± 0.11, 1.10 ± 0.08 vs 1.66 ± 0.14, P < 0.05). The colonic expression of HO-1 was not significantly different between group A and B (Western blot: proximal 0.22 ± 0.02 vs 0.22 ± 0.03; distal 0.23 ± 0.03 vs 0.23 ± 0.03; both P > 0.05), but HO-1 expression was markedly higher in group C (proximal 0.66 ± 0.09; distal 0.47 ± 0.07) than that in the former two groups (P < 0.05); the expression of HO-1 was hardly found in group D. In comparison with those in group B, the gastrointestinal propulsion rate (54.4% ± 2.9% vs 63.0% ± 1.2%, P < 0.05), spontaneous contraction frequencies, amplitudes, and reaction to acetylcholine of colonic smooth muscles were dramatically declined in group C (P < 0.05), while those (gastrointestinal propulsion rate: 72.5% ± 2.6% vs 63.0% ± 1.2%, P < 0.05) in group D were markedly improved (all P < 0.05).
CONCLUSION: HO interference has no effect on the body weight or blood glucose of diabetic rats. The induction of HO-1 may aggravate the decline of colonic motility in diabetic rats, while HO-1 blockage may improve the declined colonic motility.
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Banta CA, Clemens ET, Krinsky MM, Sheffy BE. Sites of organic acid production and patterns of digesta movement in the gastrointestinal tract of dogs. J Nutr 1979; 738:1-7. [PMID: 39123 DOI: 10.1016/j.ejphar.2014.05.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2013] [Revised: 04/29/2014] [Accepted: 05/12/2014] [Indexed: 12/12/2022] Open
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