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Ud-Din M, Karout B, Torbé WM, Lunding J, Wegeberg AM, Drewes AM, Brock C, Hellström PM. DIgestive COmplications in DIabetes - the DICODI population study. Scand J Gastroenterol 2023; 58:3-6. [PMID: 35961288 DOI: 10.1080/00365521.2022.2106149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Diabetes type 1 and type 2 may develop gastrointestinal complications e.g., gastroparesis and gastroenteropathy. Concomitant celiac disease and pancreatic exocrine insufficiency occur with high prevalence in diabetes and with symptomatic overlap. Consequently, it is a challenge to disentangle symptoms of these conditions and separate them from functional dyspepsia. We aim to develop a clinical decision-support tool to differentiate the underlying disease in a plethora of gastrointestinal symptoms. METHODS An internet-based computerized survey will collect basic characteristics (diabetes type, age, gender, duration, HbA1c, treatment) and patient reported outcomes by validated questionnaires focusing on (1) gastroparesis using Gastroparesis Cardinal Symptom Index; (2) gastroenteropathy using Gastrointestinal Symptom Rating Scale; (3) celiac disease using Celiac Symptom Index and (4) pancreatic exocrine insufficiency with Pancreatic Exocrine Insufficiency Questionnaire. Logistic regression and multiple regression analyses will identify risk factors and gastrointestinal complications. Cluster analyses and machine learning will classify different symptoms and co-existing presentations, into a likely diagnosis. We seek biomarkers for autonomic neuropathy by characterizing development of retinopathy using the Visual Function Questionnaire-25 and peripheral neuropathy by the Michigan neuropathy questionnaire. Participants are re-examined yearly for disease progression over time. RESULTS From focus group studies gastrointestinal symptoms are of major concern in diabetes. Potentially, estimates of symptom prevalence, risk factor identification and classifications of gastrointestinal complications can be unraveled for feedback to health care providers. CONCLUSION The web-based DICODI project will open up possibilities to detect gastrointestinal complications of diabetes in a societal setting, benefitting people living with diabetes, health care professionals, and society.
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Affiliation(s)
- Moeen Ud-Din
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | | | - Johan Lunding
- Diakonhjemmet Hospital, Oslo University, Oslo, Norway
| | - Anne-Marie Wegeberg
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Per M Hellström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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2
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Vélez C, Freedman SD, Assis DN. Update in Advancing the Gastrointestinal Frontier in Cystic Fibrosis. Clin Chest Med 2022; 43:743-755. [PMID: 36344078 DOI: 10.1016/j.ccm.2022.07.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Clinical complications of cystic fibrosis (CF) include a variety of gastrointestinal (GI) and hepatobiliary manifestations. Recent years have witnessed several advances in the understanding and management of these complications, in addition to opportunities for therapeutic innovations. Herein we review the current understanding of these disorders and also discuss the management of the GI and hepatobiliary complications experienced by persons with CF.
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Affiliation(s)
- Christopher Vélez
- Division of Gastroenterology, Department of Medicine, Center for Neurointestinal Health, Massachusetts General Hospital, Harvard Medical School, 15 Parkman Street Suite 535, Boston, MA 0211, USA
| | - Steven D Freedman
- Beth Israel Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
| | - David N Assis
- Section of Digestive Diseases, Yale School of Medicine, 333 Cedar Street, 1080 LMP, New Haven, CT 06510, USA.
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3
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Syrine G, Mariem MK, Hend K, Imed L. Relationship Between Esophageal Motility Disorders and Autonomic Nervous System in Diabetic Patients: Pilot North African Study. Am J Mens Health 2022; 16:15579883221098588. [PMID: 35562861 PMCID: PMC9112418 DOI: 10.1177/15579883221098588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Little attention has been given to esophageal disorders in diabetes mellitus. Pathophysiology of esophageal motility disorders (EMD) in patients with diabetes mellitus is multifactorial. The aims of the present study were: (a) to evaluate the prevalence of EMD in patients with Type 2 diabetes mellitus and (b) to determine the relationship between EMD and autonomic neuropathy as assessed by heart rate variability (HRV). All the patients completed a questionnaire about diabetes characteristics and gastrointestinal symptoms. Conventional esophageal manometry was performed in all patients. HRV was measured in three different situations (Lying Position 1, standing position, and Lying Position 2). The temporal and frequency domain parameters were considered for analysis. The prevalence of EMD in our patients was 60.5% (n = 23). Low score physical activity was significantly more frequent in patients with EMD (p = .03). There was an increase in sympathetic activity represented by the low frequency (LF) parameter (p = .027) in the presence of EMD. Whereas parasympathetic modulation of heart rate represented by the high frequency (HF) parameter (p = .027) was declined in patients with EMD compared to those without. The LF/HF ratio was significantly higher (p = .002) in patients with EMD. EMD were prevalent in diabetes mellitus and were associated to autonomic nervous system dysfunction predominantly at the parasympathetic component.
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Affiliation(s)
- Gallas Syrine
- Research Laboratory, "Technologies et Imagerie Médicale" (LR12ES06), Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.,Department of Nervous System Exploration, Sahloul Hospital, Sousse, Tunisia
| | | | - Knaz Hend
- Research Laboratory, "Technologies et Imagerie Médicale" (LR12ES06), Faculty of Medicine of Monastir, University of Monastir, Monastir, Tunisia.,Department of Nervous System Exploration, Sahloul Hospital, Sousse, Tunisia
| | - Latiri Imed
- Laboratory of Physiology, Faculty of Medicine of Sousse, University of Sousse, Sousse, Tunisia.,Research Laboratory, "Heart Failure" (LR12SP09), Farhat Hached University Hospital, Sousse, Tunisia
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Svistunov AA, Osadchuk MA, Mironova ED, Guliaev PV, Vasileva IN. The role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin in the occurrence of cholelithiasis. TERAPEVT ARKH 2022; 94:194-199. [DOI: 10.26442/00403660.2022.02.201370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 03/28/2022] [Indexed: 11/22/2022]
Abstract
Aim. To establish the role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin (M-cells) in the occurrence of cholelithiasis.
Materials and methods. The first group included 122 patients with cholelithiasis. The second group consisted of 30 healthy individuals who underwent medical examination. The groups were matched for gender and age. The work analyzed anamnestic, biochemical and anthropometric data. All patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucous membrane from the antrum. Biopsies were subjected to cytological and immunohistochemical studies in order to verify Helicobacter pylori and estimate the number of M-cells.
Results. Patients with cholelithiasis more often belonged to the group of people of mental labor, had low physical activity, were committed to inappropriate nutrition and more often indicated the presence of aggravated heredity for cholelithiasis. Patients with gallstone disease had higher body mass index, waist volume, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, lower high-density lipoprotein cholesterol, H. pylori infection was more often verified and M-cell hypoplasia in the mucous membrane was established. stomach in comparison with the representatives of the second group.
Conclusion. Our results suggest that certain external factors, nutritional characteristics of the metabolic syndrome components, hypoplasia of M-cells in the gastric mucosa are important factors in the formation of calculi in the gallbladder.
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5
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Kazeminia M, Salari N, Shohaimi S, Akbari H, Mohammadi M. Prevalence of gastrointestinal complications in patients with type 2 diabetes mellitus in Iran: a systematic review and meta-analysis. J Diabetes Metab Disord 2022; 21:1029-1036. [PMID: 35673410 PMCID: PMC9167313 DOI: 10.1007/s40200-022-00974-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 01/03/2022] [Indexed: 01/16/2023]
Abstract
Background Type 2 diabetes is the most common diabetes in the world and constitutes a high percentage of diabetes cases. This study aims to determine the overall prevalence of gastrointestinal complaints in Iranian patients with type 2 diabetes. Methods The articles were extracted based on entry and exit criteria by searching the Cochrane (Embase), ScienceDirect databases. Scopus PubMed; And Web of Science (WoS), based on PRISMA 2009. To evaluate the studies, a 22-item STROBE checklist was selected and related items were used. Results The probability of publication bias in reporting the results was examined by the Egger test (P = 0.891). The prevalence rate of gastrointestinal complaints in patients with type 2 diabetes in Iran in 10 studies was 52.3% (95% CI: 33.4-70.7%). The results of metargression showed a significant difference between the sample size and the prevalence of gastrointestinal complaints in patients with type 2 diabetes (P < 0.05). and the prevalence of gastrointestinal complaints in patients with type 2 diabetes. Conclusion The results of this study report that, the prevalence of gastrointestinal complications in type 2 diabetes patients was high. As a result, appropriate measures should be taken to improve the condition of diabetic patients through appropriate policy-making and providing feedback to hospitals and patients.
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Affiliation(s)
- Mohsen Kazeminia
- Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nader Salari
- Department of Biostatistics, School of Health, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Shamarina Shohaimi
- Department of Biology, Faculty of Science, University Putra Malaysia, Serdang, Selangor Malaysia
| | - Hakimeh Akbari
- Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran
| | - Masoud Mohammadi
- Cellular and Molecular Research Center, Gerash University of Medical Sciences, Gerash, Iran
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6
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Borle NC, Ryan EA, Greiner R. The challenge of predicting blood glucose concentration changes in patients with type I diabetes. Health Informatics J 2021; 27:1460458220977584. [PMID: 33504254 DOI: 10.1177/1460458220977584] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Patients with Type I Diabetes (T1D) must take insulin injections to prevent the serious long term effects of hyperglycemia. They must also be careful not to inject too much insulin because this could induce (potentially fatal) hypoglycemia. Patients therefore follow a "regimen" that determines how much insulin to inject at each time, based on various measurements. We can produce an effective regimen if we can accurately predict a patient's future blood glucose (BG) values from his/her current features. This study explores the challenges of predicting future BG by applying a number of machine learning algorithms, as well as various data preprocessing variations (corresponding to 312 [learner, preprocessed-dataset] combinations), to a new T1D dataset that contains 29,601 entries from 47 different patients. Our most accurate predictor, a weighted ensemble of two Gaussian Process Regression models, achieved a (cross-validation) errL1 loss of 2.7 mmol/L (48.65 mg/dl). This result was unexpectedly poor given that one can obtain an errL1 of 2.9 mmol/L (52.43 mg/dl) using the naive approach of simply predicting the patient's average BG. These results suggest that the diabetes diary data that is typically collected may be insufficient to produce accurate BG prediction models; additional data may be necessary to build accurate BG prediction models over hours.
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Affiliation(s)
| | - Edmond A Ryan
- University of Alberta, Canada.,Alberta Diabetes Institute, Canada
| | - Russell Greiner
- University of Alberta, Canada.,Alberta Machine Intelligence Institute, Canada
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7
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Rahmani B, Gandhi J, Joshi G, Smith NL, Reid I, Khan SA. The Role of Diabetes Mellitus in Diseases of the Gallbladder and Biliary Tract. Curr Diabetes Rev 2020; 16:931-948. [PMID: 32133965 DOI: 10.2174/1573399816666200305094727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 02/18/2020] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increasing prevalence of diabetes mellitus worldwide continues to pose a heavy burden. Though its gastrointestinal impact is appropriately recognized, the lesser known associations may be overlooked. OBJECTIVE We aim to review the negative implications of diabetes on the gallbladder and the biliary tract. METHODS A MEDLINE® database search of literature was conducted with emphasis on the previous five years, combining keywords such as "diabetes," "gallbladder," and "biliary". RESULTS The association of diabetes to the formation of gallstones, gallbladder cancer, and cancer of the biliary tract are discussed along with diagnosis and treatment. CONCLUSION Though we uncover the role of diabetic neuropathy in gallbladder and biliary complications, the specific individual diabetic risk factors behind these developments is unclear. Also, in addition to diabetes control and surgical gallbladder management, the treatment approach also requires further focus.
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Affiliation(s)
- Benjamin Rahmani
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Jason Gandhi
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Medical Student Research Institute, St. George’s University School of Medicine, Grenada, West Indies
| | - Gunjan Joshi
- Department of Internal Medicine, Stony Brook Southampton Hospital, Southampton, NY, USA
| | | | - Inefta Reid
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Sardar Ali Khan
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Department of Urology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
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8
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Asgharnezhad M, Joukar F, Fathalipour M, Khosousi M, Hassanipour S, Pourshams A, Mansour-Ghanaei R, Mansour-Ghanaei F. Gastrointestinal symptoms in patients with diabetes mellitus and non-diabetic: A cross-sectional study in north of Iran. Diabetes Metab Syndr 2019; 13:2236-2240. [PMID: 31235163 DOI: 10.1016/j.dsx.2019.05.028] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 05/24/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Gastrointestinal (GI) symptoms are common in patients with diabetes mellitus (DM), which involved in high cost of health care and low quality of life. The aim of this study to investigate the prevalence of GI symptoms in diabetic patients referred to the Gastrointestinal and Liver Diseases Research Center (GLDRC), Guilan University of Medical Sciences (Rasht, Iran) using a validated questionnaire. METHODS In this descriptive, cross-sectional study, 255 diabetic patients and 255 non-diabetic subjects were recruited. Participants were randomly selected. The questionnaire recorded GI symptoms among the study population. RESULTS GI symptoms were reported in 91.4% of diabetic patients, and 42.1% of them were male. The common GI symptoms in diabetic patients were flatulence (33.0%), followed by retrosternal pain (14.9%), belching (13.7%), postprandial fullness (12.5%), and constipation (11.4%). Retrosternal pain, constipation, flatulence, loss of appetite, and abdominal distention were more prevalent in diabetic women than men. CONCLUSIONS DM is associated with high prevalence rate of upper and lower GI symptoms. This effect may be linked to gender and poor glycemic control in diabetic patients, but not to type and duration of diabetes.
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Affiliation(s)
- Mehrnaz Asgharnezhad
- Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran; GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammad Fathalipour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Mohammadjavad Khosousi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Soheil Hassanipour
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran; Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Akram Pourshams
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Roya Mansour-Ghanaei
- Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Fariborz Mansour-Ghanaei
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran; Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.
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9
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Tao W, Dong X, Kong G, Fang P, Huang X, Bo P. Elevated Circulating hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b in Type 2 Diabetes Mellitus with Diarrhea-Predominant Irritable Bowel Syndrome. Gastroenterol Res Pract 2016; 2016:9256209. [PMID: 27635130 PMCID: PMC5011218 DOI: 10.1155/2016/9256209] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 04/26/2016] [Indexed: 12/15/2022] Open
Abstract
Background and Aims. Although the differential expression of microRNA (miRNA) genes has been identified in many diseases, little information exists concerning the miRNA expression profile in type 2 diabetes mellitus (T2DM) with diarrhea-predominant irritable bowel syndrome (D-IBS). Therefore, the specific expression of miRNAs in diabetes with D-IBS is identified in the study. Materials and Methods. 201 patients with IBS and 220 matched healthy controls were included in the study. Microarray technology and real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) were taken to examine the miRNA expression profiles of T2DM patients with diarrhea-predominant irritable bowel syndrome (D-IBS) compared with patients with T2DM, patients with D-IBS, and control subjects. Results. We have found that 35 miRNAs were differentially expressed in T2DM with D-IBS, in which three representative miRNAs, hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b, were found to be significantly elevated in T2DM with D-IBS by RT-PCR. Conclusions. Our study has indicated that hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b were elevated in T2DM with D-IBS, which may be the potential biomarkers of T2DM with D-IBS. To obtain a better understanding of the biological functions of these miRNAs in T2DM with D-IBS, functional annotation analysis suggested that the MAPK pathway may be responsible for T2DM with D-IBS.
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Affiliation(s)
- Wenhua Tao
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Xiaoyun Dong
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Guimei Kong
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Penghua Fang
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Xiaoli Huang
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
| | - Ping Bo
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical School of Yangzhou University, No. 11 Huaihai Road, Yangzhou, Jiangsu 225001, China
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10
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The association between gallstones and metabolic syndrome in urban Han Chinese: a longitudinal cohort study. Sci Rep 2016; 6:29937. [PMID: 27443986 PMCID: PMC4957232 DOI: 10.1038/srep29937] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Accepted: 06/27/2016] [Indexed: 12/11/2022] Open
Abstract
The precise association between metabolic syndrome (MetS) and gallstone disease remains unclear in China. This study aimed to clarify the relationship between MetS and gallstone and evaluate whether counts of metabolic abnormalities had influence on gallstone disease. We fitted gender-specific generalized estimating equation (GEE) regression models with data from a large-scale longitudinal study over 6-year follow-up to elucidate the real association. This study included 18291 participants with 3 times repeated measures at least who were free from a prior history of gallstone disease and cholecystectomy. A total of 873 cases of gallstones occurred during 6-year follow-up. The incidence density of gallstone in the group of subjects with MetS was higher than the group without MetS (10.27 vs 5.79). The GEE analyses confirmed and clarified the association between MetS and gallstone disease in males (RR = 1.33, P = 0.0020), while this association was not significant in females (RR = 1.15, P = 0.4962). With numbers of metabolic syndrome components increasing, the risk of gallstone disease showed corresponding increasing in males. In conclusion, the associations of MetS and gallstone are different in males and in females. And the risk of gallstone disease increases with the number of components of MetS for males but not for females.
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11
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Punjabi P, Hira A, Prasad S, Wang X, Chokhavatia S. Review of gastroesophageal reflux disease (GERD) in the diabetic patient. J Diabetes 2015; 7:599-609. [PMID: 25706050 DOI: 10.1111/1753-0407.12279] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 12/18/2014] [Accepted: 02/07/2015] [Indexed: 12/13/2022] Open
Abstract
This article reviews the known pathophysiological mechanisms of comorbid gastroesophageal reflux disease (GERD) in the diabetic patient, discusses therapeutic options in care, and provides an approach to its evaluation and management. We searched for review articles published in the past 10 years through a PubMed search using the filters diabetes mellitus, GERD, pathophysiology, and management. The search only yielded a handful of articles, so we independently included relevant studies from these review articles along with related citations as suggested by PubMed. We found diabetic patients are more prone to developing GERD and may present with atypical manifestations. A number of mechanisms have been proposed to elucidate the connection between these two diseases. Studies involving treatment options for comorbid disease suggest conflicting drug-drug interactions. Currently, there are no published guidelines specifically for the evaluation and management of GERD in the diabetic patient. Although there are several proposed mechanisms for the higher prevalence of GERD in the diabetic patient, this complex interrelationship requires further research. Understanding the pathophysiology will help direct diagnostic evaluation. In our review, we propose a management algorithm for GERD in the diabetic patient.
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Affiliation(s)
- Paawan Punjabi
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Angela Hira
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Shanti Prasad
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Xiangbing Wang
- Division of Endocrinology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | - Sita Chokhavatia
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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12
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Park KS. Impact of myenteric plexus alterations on diabetes related gastrointestinal dysmotility. J Neurogastroenterol Motil 2013; 19:121-3. [PMID: 23667742 PMCID: PMC3644647 DOI: 10.5056/jnm.2013.19.2.121] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2012] [Revised: 02/06/2013] [Accepted: 02/06/2013] [Indexed: 01/27/2023] Open
Affiliation(s)
- Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
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13
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de Kort S, Kruimel JW, Sels JP, Arts ICW, Schaper NC, Masclee AAM. Gastrointestinal symptoms in diabetes mellitus, and their relation to anxiety and depression. Diabetes Res Clin Pract 2012; 96:248-55. [PMID: 22325156 DOI: 10.1016/j.diabres.2012.01.021] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2010] [Revised: 01/11/2012] [Accepted: 01/16/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prevalence of gastrointestinal (GI) symptoms is increased in patients with diabetes mellitus. In general, GI symptoms are influenced by psychological factors such as anxiety and depression, but little is known about this association in diabetic patients. AIM We tested the hypothesis that anxiety and depression have major impact on GI symptoms in diabetic patients. METHODS 280 diabetic patients and 355 non-diabetic, age and sex matched controls were studied by validated questionnaires: (1) PAGI-SYM and GSRS for common GI symptoms and (2) HADS for anxiety and depression. Data were compared using logistic regression analysis. RESULTS Patients with diabetes scored significantly (p<0.05) higher on the symptoms diarrhea (OR 1.64, 95% CI 1.05-2.56), early satiety (OR 2.50, 95% CI 1.39-4.49) and bloating (OR 1.58, 95% CI 1.03-2.43), but not on other symptoms. Prevalence of anxiety and depression (HADS scores ≥ 8) in diabetics and controls was respectively 27.5% and 20.6% for anxiety (p<0.05), and 19.6% and 13.4% for depression (p<0.05). After adjusting for anxiety and depression only the GI symptom "early satiety" remained significantly more prevalent in the patients with diabetes. CONCLUSIONS The prevalence of the gastrointestinal symptoms diarrhea, bloating and early satiety, and of anxiety and depression is significantly increased in our cohort of predominantly patients with longstanding type 2 diabetes mellitus compared to controls. When adjusted for anxiety and depression, only the gastrointestinal symptom "early satiety" remained more prevalent in these diabetic patients, pointing to a somatic based origin. Thus, in our diabetic population psychological factors to a large extent are associated with gastrointestinal symptoms and should be taken into account when considering treatment of the gastrointestinal symptoms.
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Affiliation(s)
- Sander de Kort
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
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14
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Kim SJ, Park JH, Song DK, Park KS, Lee JE, Kim ES, Cho KB, Jang BK, Chung WJ, Hwang JS, Kwon JG, Kim TW. Alterations of colonic contractility in long-term diabetic rat model. J Neurogastroenterol Motil 2011; 17:372-80. [PMID: 22148106 PMCID: PMC3228977 DOI: 10.5056/jnm.2011.17.4.372] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2011] [Revised: 07/28/2011] [Accepted: 08/06/2011] [Indexed: 12/28/2022] Open
Abstract
Background/Aims Dysfunction of the gastrointestinal tract occurs in about 76% of patients who are diabetic for more than 10 years. Although diabetes-related dysfunctions of the stomach such as gastroparesis have been extensively studied over the recent years, studies about the mechanism underlying colonic symptoms in long-term diabetes models are rare. Therefore, the goal of our study was to clarify the nature of colonic dysfunction in a long-term diabetic rat model. Methods The characteristics of colonic smooth muscle were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. These results were compared to those obtained from Long-Evans Tokushima Otsuka (LETO) control rats. Results Spontaneous contractility of the proximal colon was significantly decreased in the diabetic rats compared to the controls, while the spontaneous contractility of the distal colon was not. The number of interstitial cells of Cajal networks in the proximal colon was greatly decreased in diabetic rats compared to the controls. Contractility of the proximal colon in response to carbachol, an acetylcholine receptor agonist, was significantly weaker in the diabetic rats. In addition, the degree of relaxation in response to nitric oxide in the proximal colon of diabetic rats also appeared to be attenuated. Conclusions The results from our study suggest that the decrease of interstitial cells of Cajal network, cholinergic receptors, and neuronal nitric oxide synthase in the proximal colon plays important roles in diabetes-related dysfunction of colon.
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Affiliation(s)
- Sun Joo Kim
- Department of Physiology, Keimyung University School of Medicine, Daegu, Korea
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Câmara PR, Moi GP, Ferraz JGP, Zeitune JMR. Effect of anesthetics on gastric damage using two models of portal hypertension. World J Gastrointest Pharmacol Ther 2010; 1:81-6. [PMID: 21577313 PMCID: PMC3091276 DOI: 10.4292/wjgpt.v1.i4.81] [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] [Received: 01/20/2010] [Revised: 02/16/2010] [Accepted: 02/23/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of sodium pentobarbitone (SP) or ketamine/xylazine (KX) anesthetics on acute gastric injury.
METHODS: Portal hypertension was induced by bile duct ligation (BDL) or portal vein stenosis (PVS). Ethanol (EtOH)-induced gastric damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow (GBF) was also measured by laser doppler flowmetry.
RESULTS: EtOH-induced gastric damage was reduced in BDL rats under KX anesthesia in comparison to those under SP anesthesia. GBF dysfunction in fasted BDL rats was partially restored under KX anesthesia. In contrast, in fasted PVS rats, EtOH-induced gastric damage was increased under KX anesthesia while GBF was reduced.
CONCLUSION: The use of KX anesthesia in experimental procedures involving cirrhotic rats (but not those with pure portal hypertension) is preferable to SP anesthesia.
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Affiliation(s)
- Paula Rs Câmara
- Paula RS Câmara, Gisele P Moi, UNIVAG, University Center of Várzea Grande, Mato Grosso, Brazil
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16
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Esophageal function worsens with long duration of diabetes. J Gastroenterol 2008; 43:338-44. [PMID: 18592151 DOI: 10.1007/s00535-008-2169-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2007] [Accepted: 02/12/2008] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to assess the relationship between the duration of diabetes and esophageal dysfunction. METHODS We examined 66 patients with type 2 diabetes. Duration of diabetes was determined by asking patients and from their medical records. The patients were divided into three groups according to the duration of their diabetes: group A, 1-4 years, n=26; group B, 5-9 years, n=20; and group C, 10+ years, n=20. Ambulatory esophageal 24-h pH and motility were monitored, and gastroesophageal reflux and esophageal motility disorders were estimated in detail. RESULTS When the duration of diabetes was long, the percentage of time with pH<4 tended to increase. The amplitude of esophageal peristaltic waves and the frequency of effective peristalsis were reduced when the duration of diabetes was long. A significant correlation was observed between the duration of diabetes and the frequency of effective peristalsis. The number of esophageal peristaltic waves per minute and the percentage of multipeaked peristaltic waves increased significantly in group B, and decreased when the duration of diabetes became longer. CONCLUSIONS Gastroesophageal reflux and esophageal motility disorders worsened with long duration of diabetes. These esophageal dysfunctions should be considered in patients with long-standing diabetes.
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Zhou SY, Lu YX, Owyang C. Gastric relaxation induced by hyperglycemia is mediated by vagal afferent pathways in the rat. Am J Physiol Gastrointest Liver Physiol 2008; 294:G1158-64. [PMID: 18356537 PMCID: PMC3217037 DOI: 10.1152/ajpgi.00067.2008] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hyperglycemia has a profound effect on gastric motility. However, little is known about the site and mechanism that sense alteration in blood glucose level. The identification of glucose-sensing neurons in the nodose ganglia led us to hypothesize that hyperglycemia acts through vagal afferent pathways to inhibit gastric motility. With the use of a glucose-clamp rat model, we showed that glucose decreased intragastric pressure in a dose-dependent manner. In contrast to intravenous infusion of glucose, intracisternal injection of glucose at 250 and 500 mg/dl had little effect on intragastric pressure. Pretreatment with hexamethonium, as well as truncal vagotomy, abolished the gastric motor responses to hyperglycemia (250 mg/dl), and perivagal and gastroduodenal applications of capsaicin significantly reduced the gastric responses to hyperglycemia. In contrast, hyperglycemia had no effect on the gastric contraction induced by electrical field stimulation or carbachol (10(-5) M). To rule out involvement of serotonergic pathways, we showed that neither granisetron (5-HT(3) antagonist, 0.5 g/kg) nor pharmacological depletion of 5-HT using p-chlorophenylalanine (5-HT synthesis inhibitor) affected gastric relaxation induced by hyperglycemia. Lastly, N(G)-nitro-L-arginine methyl ester (L-NAME) and a VIP antagonist each partially reduced gastric relaxation induced by hyperglycemia and, in combination, completely abolished gastric responses. In conclusion, hyperglycemia inhibits gastric motility through a capsaicin-sensitive vagal afferent pathway originating from the gastroduodenal mucosa. Hyperglycemia stimulates vagal afferents, which, in turn, activate vagal efferent cholinergic pathways synapsing with intragastric nitric oxide- and VIP-containing neurons to mediate gastric relaxation.
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Louay Omran M, Aneed W. Nutrition and Gastrointestinal Function. NUTRITION AND DISEASE PREVENTION 2007:451-467. [DOI: 10.1201/9781420005493.ch28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Tung TH, Ho HM, Shih HC, Chou P, Liu JH, Chen VTK, Chan DC, Liu CM. A population-based follow-up study on gallstone disease among type 2 diabetics in Kinmen, Taiwan. World J Gastroenterol 2006; 12:4536-40. [PMID: 16874867 PMCID: PMC4125642 DOI: 10.3748/wjg.v12.i28.4536] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To assess the incidence of and risk factors for gallstone disease (GSD) among type 2 diabetics in Kinmen, Taiwan.
METHODS: A screening program for GSD was performed by two specialists who employed real-time abdominal ultrasound to examine the abdominal region after patients had fasted for at least eight hours. Screening, which was conducted in 2001, involved 848 patients diagnosed with type 2 diabetes. After exclusion of 63 subjects with prevalent GSD, 377 participants without GSD were invited in 2002 for a second round of screening. A total of 281 (74.5%) subjects were re-examined.
RESULTS: Among the 281 type 2 diabetics who had no GSD at the first screening, 10 had developed GSD by 2002. The incidence was 3.56% per year (95% CI: 1.78% per year-6.24% per year). Using a Cox regression model, age (RR = 1.07, 95% CI: 1.00-1.14), waist circumference (RR = 1.12, 95% CI: 1.01-1.29), and ALT (RR = 1.13, 95%CI: 1.01-1.26) appeared to be significantly correlated with development of GSD.
CONCLUSION: Older age is a known risk factor for the development of GSD. Our study shows that greater waist circumference and elevated ALT levels are also associated with the development of GSD among type 2 diabetics in Kinmen.
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Affiliation(s)
- Tao-Hsin Tung
- Cheng Hsin Rehabilitation Medical Center, Taipei, Taiwan; National Taipei College of Nursing, Taipei, Taiwan, China
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20
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Abstract
Gastrointestinal (GI) sensory-motor abnormalities are common in patients with diabetes mellitus and may involve any part of the GI tract. Abnormalities are frequently sub-clinical, and fortunately only rarely do severe and life-threatening problems occur. The pathogenesis of abnormal upper GI sensory-motor function in diabetes is incompletely understood and is most likely multi-factorial of origin. Diabetic autonomic neuropathy as well as acute suboptimal control of diabetes has been shown to impair GI motor and sensory function. Morphological and biomechanical remodeling of the GI wall develops during the duration of diabetes, and may contribute to motor and sensory dysfunction. In this review sensory and motility disorders of the upper GI tract in diabetes is discussed; and the morphological changes and biomechanical remodeling related to the sensory-motor dysfunction is also addressed.
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Affiliation(s)
- Jingbo Zhao
- Center of Excellence in Visceral Biomechanics and Pain, the Research Building room 404, Aalborg Hospital, Sdr. Skovvej 15, DK-9000 Aalborg, Denmark.
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21
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Shi M, Jones AR, Niedringhaus MS, Pearson RJ, Biehl AM, Ferreira M, Sahibzada N, Verbalis JG, Gillis RA. Glucose acts in the CNS to regulate gastric motility during hypoglycemia. Am J Physiol Regul Integr Comp Physiol 2003; 285:R1192-202. [PMID: 12869364 DOI: 10.1152/ajpregu.00179.2003] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Our purposes were to 1) develop an animal model where intravenously (iv) administered d-glucose consistently inhibited antral motility, and 2) use this model to assess whether iv glucose acts to inhibit motility from a peripheral or a central nervous system site and to elucidate the factor(s) that determine(s) whether stomach motor function is sensitive to changes in blood glucose. Rats were anesthetized with alpha-chloralose-urethane, and antral motility was measured by a strain-gauge force transducer sutured to the antrum. In some cases, antral motility and gastric tone were measured by monitoring intragastric balloon pressure. Increases in blood glucose were produced by continuous iv infusion of 25% d-glucose at 2 ml/h. Inhibition of antral motility and gastric tone was observed when gastric contractions were induced by hypoglycemia (subcutaneously administered insulin, 2.5 IU/animal). In contrast, no inhibition of gastric motor function was observed when glucose infusion was tested on gastric contractions that were 1) spontaneously occurring, 2) evoked by iv administered bethanechol in vagotomized animals, and 3) evoked by the TRH analog RX77368, microinjected into the dorsal motor nucleus of the vagus. Using the model of insulin-induced hypoglycemia to increase gastric motor activity, we found that neither sectioning the hepatic branch of the vagus (n = 5), nor treating animals with capsaicin to destroy sensory vagal afferent nerves (n = 5) affected the ability of iv d-glucose to inhibit gastric motor function. Our results indicate that an important factor determining whether stomach motor function will be sensitive to changes in blood glucose is the method used to stimulate gastric contractions, and that the primary site of the inhibitory action of iv glucose on gastric motility is the central nervous system rather than the periphery.
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Affiliation(s)
- Min Shi
- Dept. of Pharmacology, Georgetown Univ. Medical Center, Washington, DC 20057, USA
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Dhiman RK, Arke L, Bhansali A, Gupta S, Chawla YK. Cisapride improves gallbladder emptying in patients with type 2 diabetes mellitus. J Gastroenterol Hepatol 2001; 16:1044-50. [PMID: 11595071 DOI: 10.1046/j.1440-1746.2001.02586.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIMS Gallbladder motor function is impaired in many patients with diabetes, and may be related to cholinergic nerve damage. Cisapride is a prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine from cholinergic nerve endings. The aim of this study was to determine the effect of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus (DM). METHODS Gallbladder emptying and tests for autonomic neuropathy (AN) were performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder emptying was studied by using real-time ultrasonography after an overnight fast, and after the subjects received a breakfast that contained 2500 J. Gallbladder emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1 week in all subjects. RESULTS Abnormal gallbladder emptying was present in 14 (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3 +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0 vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects. Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs 20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003, respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/- 3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/- 2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of cholinergic receptors. There was no significant change in the ejection fraction in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level did not influence gallbladder emptying. CONCLUSION Impaired gallbladder emptying is common in patients with type 2 DM. Cisapride significantly improves gallbladder emptying in patients with autonomic neuropathy.
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Affiliation(s)
- R K Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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23
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Abstract
Diabetes mellitus affects various organs, including the gastrointestinal tract. The stomach is commonly affected, and symptoms related to the upper GI tract are frequently reported. Management of diabetic gastropathy involves dietary modifications, pharmacological agents, and occasionally, alternative feeding methods.
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Affiliation(s)
- B Shen
- Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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24
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Celik AF, Oşar Z, Damci T, Pamuk ON, Pamuk GE, Ilkova H. How important are the disturbances of lower gastrointestinal bowel habits in diabetic outpatients? Am J Gastroenterol 2001; 96:1314-6. [PMID: 11316207 DOI: 10.1111/j.1572-0241.2001.03738.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Rayner CK, Su YC, Doran SM, Jones KL, Malbert CH, Horowitz M. The stimulation of antral motility by erythromycin is attenuated by hyperglycemia. Am J Gastroenterol 2000; 95:2233-41. [PMID: 11007223 DOI: 10.1111/j.1572-0241.2000.02250.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is erythromycin. Recent studies have demonstrated that the gastrokinetic effects of erythromycin are attenuated by hyperglycemia. The aim of this study was to determine whether the effects of erythromycin on antropyloroduodenal motility, including the organization of antral pressure waves, are modified by hyperglycemia. METHODS A total of eight healthy male volunteers (median age 24 yr) were studied on 2 days each in randomized order. A manometric assembly, incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5 kcal/min) was commenced and continued until the end of the study. At T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over 20 min, followed by 100 mg over the next 40 min. RESULTS Intravenous erythromycin increased the amplitude of antral waves during intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p < 0.05) and amplitude (p < 0.01) of antral waves were less during hyperglycemia than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyperglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and amplitude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyperglycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the amplitude (p < 0.001) but not the frequency of duodenal waves; the frequency and amplitude of duodenal waves did not differ between the two blood glucose concentrations. CONCLUSIONS Hyperglycemia attenuates the stimulation of antral pressures and propagated antral sequences by erythromycin, but not the effects of erythromycin on pyloric or duodenal motility.
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Affiliation(s)
- C K Rayner
- University of Adelaide Department of Medicine, Royal Adelaide Hospital, Australia
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26
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Abstract
AIMS To examine and compare gastrointestinal (GI) symptoms in Hong Kong Chinese Type 2 diabetic outpatients and non-diabetic control subjects. METHODS A total of 149 Chinese Type 2 diabetic patients (66 men and 83 women, age (mean +/- SD) 46.8+/-11.1 years) newly referred to the diabetes clinic of the Prince of Wales Hospital, Hong Kong were examined. Sixty-five age and sex-matched non-diabetic subjects were recruited from the community as controls (22 men and 43 women, age (mean +/- SD) 46.5+/-6.6 years, P = 0.820). All patients were interviewed regarding GI symptoms over the past year, using a questionnaire that covered 14 items. A scoring system from 0 to 4 was used to grade severity. RESULTS Diabetic patients had higher blood pressure, fasting plasma glucose and glycated haemoglobin and were more often smokers than control subjects. Of the 149 diabetic subjects, 105 (70.5+/-45.8%) had GI symptoms while only 20 (30.8%) of the 65 control subjects had GI symptoms (P<0.001). The respective percentages of upper and lower GI symptoms in diabetic and normal subjects were 44.3% vs. 24.6% (P = 0.006) and 54.4% vs. 13.9% (P<0.001). The three commonest GI symptoms in diabetic patients were diarrhoea (34.9%), constipation (27.5%) and epigastric fullness (16.8%). After adjustment for age, sex, duration of diagnosed diabetes and smoking, patients with or without metformin had similar percentages or scores for GI symptoms. On multivariate analysis using age, body mass index, fasting plasma glucose, glycated haemoglobin, duration of diagnosed diabetes and presence of peripheral neuropathy as independent variables, duration of diabetes was the only independent parameter associated with total score for GI symptoms (beta = 0.116, P = 0.003), for upper GI symptoms (beta = 0.073, P = 0.005) and for lower GI symptom (beta = 0.043, P = 0.020). CONCLUSIONS Up to 70% of the Chinese Type 2 diabetic outpatients have GI symptoms, which is a much higher rate than in non-diabetic control subjects. Duration of diabetes is the most important factor associated with the presence of such GI symptoms.
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Affiliation(s)
- G T Ko
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories.
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Verghagen MA, Samsom M, Smout JP. Effects of intraduodenal glucose infusion on gastric myoelectrical activity and antropyloroduodenal motility. THE AMERICAN JOURNAL OF PHYSIOLOGY 1998; 274:G1038-44. [PMID: 9696703 DOI: 10.1152/ajpgi.1998.274.6.g1038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Intraduodenal nutrient infusions cause an inhibition of antral motility and an increase in pyloric motility. The involvement of gastric myoelectrical activity in this intestinogastric feedback was studied. Electrogastrography and antropyloroduodenal manometry were performed in 10 healthy volunteers. The effects of 20-mininfusions of 25% glucose (4 kcal/min) and saline were compared. Intraduodenal glucose infusions caused a decrease in the power of the dominant frequency in the electrogastrogram (P = 0.028), but the frequency itself remained unchanged. The total number of dysrhythmias increased (P = 0.035). An inhibition of antral motor activity (P = 0.001), an increase in the number of isolated pyloric pressure waves (P = 0.027), and an increase in basal pyloric tone (P = 0.001) were simultaneously recorded. The change in power during glucose infusion correlated positively with the change in the antral motility index (rs = 0.50, P = 0.001). It is concluded that inhibition of gastric myoelectrical activity is one of the mechanisms underlying an inhibition of motor activity in the gastric antrum.
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Affiliation(s)
- M A Verghagen
- Gastrointestinal Motility Unit, University Hospital, Utrecht, The Netherlands
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Abstract
Diabetes mellitus can lead to metabolic changes that alter normal hepatic and biliary function and structure. These alterations in hepatic and biliary function and structure are usually benign, but in certain situations lead to significant, disabling disease. This article reviews the hepatic and biliary complications of diabetes, with emphasis on epidemiology, diagnosis, and management, as well as the glucose intolerance seen in liver disease.
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Affiliation(s)
- F J Farrell
- Department of Medicine, University of California, San Francisco/Mount Zion Medical Center, San Francisco, USA
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Affiliation(s)
- M B Adams
- Department of Transplantation, Medical College of Wisconsin, Milwaukee
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Abstract
The glycemic influence on liquid gastric emptying in rats was studied. Diabetic hyperglycemia was induced by streptozotocin-treated rats further received a daily insulin injection ( 2.5 or 10 IU/kg). Immediate hyperglycemia was induced in a separate group of rats by continuous intravenous glucose infusion (44 or 88 mg/kg/min) 10 min before the experiment. Rats were killed 15 min after radiochromium feeding; then the radioactivity of stomach and small intestine were counted to obtain the gastric emptying value. Emptying in diabetic rats was delayed compared with controls (mean +/- SE: 40.9 +/- 2.6% vs. 54.2 +/- 2.8%, P < 0.01). Low-dose insulin treatment reversed the impairment, while high-dose treatment even enhanced emptying. Immediate hyperglycemia induced with two glucose infusions also inhibited gastric emptying. Present results indicate that hyperglycemia elicited with any hyperglycemic model is at least one of the important mechanisms to delay liquid gastric emptying.
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Affiliation(s)
- F Y Chang
- Division of Gastroenterology, Veterans General Hospital-Taipei, Taiwan
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Faigel DO, Metz DC. Prevalence, etiology, and prognostic significance of upper gastrointestinal hemorrhage in diabetic ketoacidosis. Dig Dis Sci 1996; 41:1-8. [PMID: 8565740 DOI: 10.1007/bf02208576] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
We reviewed the discharge records of all diabetic ketoacidosis hospitalizations over 30 months for the presence of clinically significant upper gastrointestinal hemorrhage. Of 284 hospitalizations in 193 patients, hemorrhage occurred in 26 hospitalizations (9%) in 25 patients (13%). None required invasive therapy to achieve hemostasis, and there were no bleeding recurrences and no deaths due to bleeding. Endoscopy in eight revealed esophagitis in all (five had erosions or ulcerations), one Mallory-Weiss tear, five with gastritis (mild in four), four with duodenitis (one erosive), one duodenal ulcer, and no gastric ulcers. Hemorrhage patients had a longer diabetes duration (14.85 vs 9.16 years, P < 0.02), and more nephropathy (40% vs 11%, P < 0.001), retinopathy (28% vs 12%, P < 0.03) and gastroparesis (36% vs 10%, P < 0.002) than those without hemorrhage. Ulcer medication (42% vs 23%, P < 0.03) or anticoagulant (12% vs 1%, P < 0.005) but not nonsteroidal antiinflammatory drug usage (12% vs 12%) was higher in the hemorrhage group. Admission glucose (P < 0.02), BUN (P < 0.04), and creatinine (P < 0.02) levels were higher in hemorrhage patients, but arterial pH, serum ketones, hemoglobin, platelet count, and coagulation values were not. Hemorrhage patients required more blood transfusions (27% vs 10%, P < 0.003) and intensive care unit admissions (69% vs 43%, P < 0.009). Total (15% vs 3%, P < 0.003) and intensive care unit mortality (22% vs 6%, P < 0.026) were higher in the hemorrhage group. We conclude that upper gastrointestinal hemorrhage complicates 9% of diabetic ketoacidosis hospitalizations. Blood transfusion may be required, but the bleeding is self-limited and not severe. The most common lesion is erosive esophagitis. Hemorrhage correlates with glucose level, admission to the intensive care unit, duration of diabetes, the presence of diabetic complications, and portends a high non-bleeding-related mortality.
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Affiliation(s)
- D O Faigel
- Department of Internal Medicine, University of Pennsylvania, Philadelphia 19104, USA
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Chang FY, Lee SD, Yeh GH, Wang PS. Hyperglycaemia is responsible for the inhibited gastrointestinal transit in the early diabetic rat. ACTA PHYSIOLOGICA SCANDINAVICA 1995; 155:457-62. [PMID: 8719265 DOI: 10.1111/j.1748-1716.1995.tb09995.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The effect of plasma glucose levels on the gastrointestinal motility of the rat was studied. Chronic hyperglycaemia was induced by i.v. injection of streptozotocin 1 week before the motility experiment. Some rats received additional daily insulin therapy (1.25, 2.5 or 10 IU kg-1) after induction of diabetes mellitus. Acute hyperglycaemia was induced by the continuous i.v. infusion of glucose solution (11, 22, 44 or 88 mg kg-1 min-1) 10 min before the motility experiments. The rats were killed 15 min after successful orogastric feeding of a charcoal-contained suspension. Gastrointestinal transit was calculated as the percentage of the overall length of the small intestine to which the charcoal moved during this time period. The diabetic rats were found to have delayed transit compared with controls (mean +/- SEM: 32.2 +/- 2.1% vs. 42.9 +/- 4.2%, P < 0.05). Correction of hyperglycaemia with moderate doses of insulin therapy failed to inhibit transit, whereas hypoglycaemia induced by high-dose insulin treatment enhanced transit. High doses of glucose elicited acute hyperglycaemia and delayed transit when compared with saline infused non-diabetic rats. In early diabetes, hyperglycaemia probably mediates the inhibited gastrointestinal transit, since correction of hyperglycaemia usually restores the delayed transit.
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Affiliation(s)
- F Y Chang
- Division of Gastroenterology, Veterans General Hospital-Taipei, Republic of China
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Chey WD, Kim M, Hasler WL, Owyang C. Hyperglycemia alters perception of rectal distention and blunts the rectoanal inhibitory reflex in healthy volunteers. Gastroenterology 1995; 108:1700-8. [PMID: 7768374 DOI: 10.1016/0016-5085(95)90131-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND/AIMS Acute hyperglycemia has been shown to alter gastrointestinal motility. The effects of hyperglycemia on rectal afferent neural and anal sphincter function were studied. METHODS Perception of rectal balloon distention, pressure-volume relationships, volumes necessary to induce reflex internal anal sphincter relaxation, resting anal sphincter pressure, and maximal anal sphincter squeeze pressure were measured under basal, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions in 9 healthy volunteers. RESULTS Hyperglycemic clamping (258 +/- 14 mg/dL) significantly blunted threshold perception and the urge to defecate in response to rectal distention without altering perception of maximally tolerated distention. In contrast, euglycemic, hyperinsulinemic clamping had no effect on perception of rectal distention. Rectal pressure-volume relationships after hyperglycemic clamping were unchanged compared with basal conditions. Hyperglycemic clamping caused a significant increase in the distention necessary to induce the rectoanal inhibitory reflex. This effect was not observed under euglycemic, hyperinsulinemic clamp conditions. Hyperglycemia did not significantly affect resting internal anal sphincter pressure or maximal external anal sphincter squeeze pressure. CONCLUSIONS Acute hyperglycemia but not secondary hyperinsulinemia reduces sensation of rectal distention and blunts the onset of the rectoanal inhibitory reflex, suggesting effects both on visceral afferents projecting to the cortex and intrinsic afferents mediating local reflex activity.
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Affiliation(s)
- W D Chey
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA
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Young AA, Gedulin B, Vine W, Percy A, Rink TJ. Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin. Diabetologia 1995; 38:642-8. [PMID: 7672483 DOI: 10.1007/bf00401833] [Citation(s) in RCA: 130] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Gastric emptying was measured in normal and insulin-treated spontaneously diabetic BB rats using the retention of an acaloric methylcellulose gel containing phenol red delivered by gavage. Dye content in stomachs removed after killing 20 min later was determined spectroscopically, and was compared to that in rats killed immediately after gavage to assess emptying. Diabetic rats had a markedly greater gastric emptying (90.3 +/- 1.7% passed) compared to normal Harlan Sprague Dawley rats (49.1 +/- 4.7% passed; p < 0.001) and non-diabetic BB rats (61.1 +/- 9.2% passed; p < 0.001). The pancreatic beta-cell peptide, amylin, which is deficient in insulin-dependent diabetes mellitus, dose-dependently inhibited gastric emptying in both normal and diabetic rats. The ED50 of the response in normal rats measured by phenol red and novel [3-3H]glucose gavage techniques was approximately 0.4 microgram. This dose was estimated to increase plasma amylin concentration by a mean of approximately 20 pmol/l to concentrations within the range observed in vivo. It is proposed that amylin could participate in the physiological control of nutrient entry into the duodenum and that the accelerated gastric emptying seen in BB rats could be related to their lack of amylin secretion.
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Affiliation(s)
- A A Young
- Amylin Pharmaceuticals Inc., San Diego, California, USA
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Björnsson ES, Urbanavicius V, Eliasson B, Attvall S, Smith U, Abrahamsson H. Effects of insulin and beta-adrenergic blockade on the migrating motor complex in humans. Scand J Gastroenterol 1995; 30:219-24. [PMID: 7770710 DOI: 10.3109/00365529509093267] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Interdigestive small-intestinal motility is suppressed by hyperglycemia and also by hyperinsulinemia per se. Since hyperinsulinemia may increase sympathetic activity, the present study was undertaken to ascertain to what extent insulin affects phase III of the migrating motor complex (MMC) and MMC-related duodenal retroperistalsis and whether beta-adrenergic receptors may mediate the effects of insulin. METHODS Fasting motility was studied in eight healthy volunteers on three occasions with an eight-lumen perfused pressure catheter, with closely spaced recording points in the proximal duodenum. On the control day 5-h antroduodenojejunal manometry was performed. On another study day euglycemic hyperinsulinemic clamping was performed for 2 h after an initial basal recording. On a 3rd day motility was recorded during propranolol infusion, combined with a period of euglycemic hyperinsulinemia. RESULTS During hyperinsulinemia complete absence of phase III of the MMC in the gastric antrum was observed, whereas 55% of the MMC had a gastric phase-III component on the control day. The duration of phase III in the proximal duodenum was decreased during hyperinsulinemia compared with the control period (p < 0.05). This inhibitory effect of insulin on the activity front was not prevented by beta blockade. Under control conditions the proportion of retroperistaltic pressure waves in the proximal duodenum was 13 +/- 8% in early phase III, increasing in late phase III to 79 +/- 15% (p < 0.01). Duodenal phase III during hyperinsulinemia showed a similar increase in retroperistalsis, from 4 +/- 4% in early phase III to 67 +/- 21% in late phase III (p < 0.01). The corresponding proportions during beta blockade were 16 +/- 10% and 86 +/- 14%, respectively. CONCLUSIONS Hyperinsulinemia per se abolishes antral phase III and makes the duodenal phase III shorter but does not interrupt the distinct pattern of retroperistalsis in late phase III. Beta-adrenergic receptors seem not to be important for these effects of insulin or for the retroperistalsis in duodenal phase III.
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Affiliation(s)
- E S Björnsson
- Division of Gastroenterology, University of Göteborg, Sahlgren's Hospital, Sweden
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Sims MA, Hasler WL, Chey WD, Kim MS, Owyang C. Hyperglycemia inhibits mechanoreceptor-mediated gastrocolonic responses and colonic peristaltic reflexes in healthy humans. Gastroenterology 1995; 108:350-9. [PMID: 7835576 DOI: 10.1016/0016-5085(95)90060-8] [Citation(s) in RCA: 69] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND/AIMS The effects of hyperglycemia on colonic motor function are unknown. Therefore, colonic neuromuscular function was tested in normal volunteers as a model for constipation in diabetes. METHODS Extended (gastrocolonic response) and local (peristaltic reflex) neural responses and colonic muscle contractility were tested under control, hyperglycemic clamp, and euglycemic, hyperinsulinemic clamp conditions with placement of barostat-regulated balloons in the descending colon to measure changes in tone as differences in balloon volume. RESULTS Hyperglycemic clamping to 274 +/- 3 mg/dL blunted increases in colon tone evoked by gastric distention (gastrocolonic response) (100-300 mL) but did not affect gastric tone. Three descending colonic balloons in series assessed the peristaltic reflex. Inflation of the middle stimulus balloon increased proximal tone, an increase that was blunted by hyperglycemia, but produced distal relaxation followed by increases in tone that were unaffected by hyperglycemia. Euglycemic, hyperinsulinemic clamping had no effect on the gastrocolonic response or peristaltic reflex. Tonic increases evoked by bethanechol (5 mg administered subcutaneously) were unaffected by hyperglycemic clamping. CONCLUSIONS Hyperglycemia blunts mechanoreceptor-mediated gastrocolonic responses and ascending contractions but not descending components of the peristaltic reflex in humans, effects not caused by hyperinsulinemia or direct muscle actions. These inhibitory effects on long and short neural reflexes that modulate colonic motility may contribute to constipation in diabetes.
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Affiliation(s)
- M A Sims
- Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor
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Björnsson ES, Urbanavicius V, Eliasson B, Attvall S, Smith U, Abrahamsson H. Effects of hyperglycemia on interdigestive gastrointestinal motility in humans. Scand J Gastroenterol 1994; 29:1096-104. [PMID: 7886397 DOI: 10.3109/00365529409094894] [Citation(s) in RCA: 74] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gastrointestinal motility disorders are common in patients with diabetes mellitus. Recent studies indicate that hyperglycemia can affect gastric emptying and gastric motility in healthy subjects and diabetics. METHODS The effect of acute hyperglycemia on gastrointestinal motility was studied with a manometric technique in healthy subjects. Seven individuals, four men and three women, 23-34 years old, were studied on 2 different days. On 1 of the days a 5-h registration was performed after an overnight fast. On another day and after an initial basal period, acute steady-state hyperglycemia was induced by intravenous glucose infusion for 90 min. Motility variables were evaluated in four segments: in the gastric antrum, the proximal duodenum, the distal duodenum, and the proximal jejunum. RESULTS Fasting migrating motor complex rhythm including migration of phase III prevailed during hyperglycemia. Compared with euglycemia, the motility index in phase II was lower during hyperglycemia in all segments studied. In the antrum the difference was 62% (p < 0.01); in the proximal duodenum, 37% (p < 0.01); in the distal duodenum, 44% (p < 0.05); and in the jejunum, 58% (p < 0.01). During hyperglycemia the prevalence of propagated contractions in phase II was significantly lower than during euglycemia both in the antrum and the proximal duodenum. In the last part of phase III in proximal duodenum most individual contractions were propagated in orad direction compared with early phase III, and this difference persisted during hyperglycemia. The number of long clusters was significantly increased during hyperglycemia as compared with euglycemia: 2.0 +/- 0.6 per hour versus 0.4 +/- 0.14 (p < 0.01). In late phase II plasma levels of motilin and pancreatic polypeptide were significantly decreased during hyperglycemia. CONCLUSION Hyperglycemia not only reduces the motility in the stomach but also inhibits motility in both the duodenum and the jejunum. The results show that acute hyperglycemia has an important impact on small-intestinal motility.
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Affiliation(s)
- E S Björnsson
- Dept. of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
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