|
1
|
Wong HJ, Sim B, Teo YH, Teo YN, Chan MY, Yeo LLL, Eng PC, Tan BYQ, Sattar N, Dalakoti M, Sia CH. Efficacy of GLP-1 Receptor Agonists on Weight Loss, BMI, and Waist Circumference for Patients With Obesity or Overweight: A Systematic Review, Meta-analysis, and Meta-regression of 47 Randomized Controlled Trials. Diabetes Care 2025; 48:292-300. [PMID: 39841962 DOI: 10.2337/dc24-1678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/22/2024] [Indexed: 01/24/2025]
Abstract
OBJECTIVE To provide an updated synthesis on effects of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on weight, BMI, and waist circumference incorporating newer randomized controlled trials (RCTs), particularly in individuals with overweight or obesity. RESEARCH DESIGN AND METHODS We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) for RCTs published from inception to 4 October 2024. The search was limited to RCTs evaluating the use of GLP-1 RAs for mean differences from baseline in weight, BMI, and waist circumference in adults with obesity or overweight with or without diabetes. Two independent reviewers performed the literature search and data extraction, resolving disagreements via consensus or third-reviewer consultation. RESULTS Forty-seven RCTs were included, with a combined cohort of 23,244 patients. GLP-1 RAs demonstrated a mean weight reduction of -4.57 kg (95% CI -5.35 to -3.78), mean BMI reduction of -2.07 kg/m2 (95% CI -2.53 to -1.62), and mean waist circumference reduction of -4.55 cm (95% CI -5.72 to -3.38) compared with placebo. This effect was consistent across diabetes status, GLP-1 RA used, and route of administration. The greatest treatment benefit appeared to favor patients who were younger, female, without diabetes, with higher baseline weight and BMI but lower baseline HbA1c, and treated over a longer duration. Limitations include substantial statistical heterogeneity, in part due to broad inclusion criteria. However, this heterogeneity may improve generalizability by reflecting a wide range of study designs and patient populations. CONCLUSIONS GLP-1 RAs demonstrated significant weight, BMI, and waist circumference reduction benefits in this meta-analysis.
Collapse
Affiliation(s)
- Hon Jen Wong
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Bryan Sim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yao Hao Teo
- Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Yao Neng Teo
- Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Mark Y Chan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Leonard L L Yeo
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Pei Chia Eng
- Division of Endocrinology, Department of Medicine, National University Hospital, Singapore
| | - Benjamin Y Q Tan
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Division of Neurology, Department of Medicine, National University Hospital, Singapore
| | - Naveed Sattar
- School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, U.K
| | - Mayank Dalakoti
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre Singapore, Singapore
| | - Ching-Hui Sia
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Cardiology, National University Heart Centre Singapore, Singapore
| |
Collapse
|
|
2
|
Santa Maria C, O'Dell K. Dysphagia as a Manifestation of Endocrine and Metabolic Disorders. Otolaryngol Clin North Am 2024; 57:657-668. [PMID: 38575488 DOI: 10.1016/j.otc.2024.02.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
Dysphagia is a common manifestation of endocrine and metabolic diseases. Swallowing is a complex neuromuscular process, with an interplay of sensory and motor function, that has voluntary and involuntary control. Disruptions in any of these processes can cause significant dysphagia. Endocrine disorders and metabolic derangements are systemic conditions that affect multiple organ systems. They contribute to the development of neuropathies, myopathies, and motility disorders that lead to swallowing difficulty. Malnutrition and critical illness can lead to deconditioning and atrophy which can cause dysphagia, which in turn can lead to further malnutrition and deconditioning.
Collapse
Affiliation(s)
- Chloe Santa Maria
- Caruso Department of Otolaryngology Head & Neck Surgery, USC Voice Center, University of Southern California, 1537 Norfolk Street, Suite 5800, Los Angeles, CA 90033, USA
| | - Karla O'Dell
- Caruso Department of Otolaryngology Head & Neck Surgery, USC Voice Center, University of Southern California, 1537 Norfolk Street, Suite 5800, Los Angeles, CA 90033, USA.
| |
Collapse
|
|
3
|
Tang X, Chen X, Ferrari M, Walvoort MTC, de Vos P. Gut Epithelial Barrier Function is Impacted by Hyperglycemia and Secondary Bile Acids in Vitro: Possible Rescuing Effects of Specific Pectins. Mol Nutr Food Res 2024; 68:e2300910. [PMID: 38794856 DOI: 10.1002/mnfr.202300910] [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: 12/22/2023] [Revised: 04/24/2024] [Indexed: 05/26/2024]
Abstract
Gut epithelial barrier disruption is commonly observed in Western diseases like diabetes and inflammatory bowel disease (IBD). Enhanced epithelial permeability triggers inflammatory responses and gut microbiota dysbiosis. Reduced bacterial diversity in IBD affects gut microbiota metabolism, altering microbial products such as secondary bile acids (BAs), which potentially play a role in gut barrier regulation and immunity. Dietary fibers such as pectin may substitute effects of these BAs. The study examines transepithelial electrical resistance of gut epithelial T84 cells and the gene expression of tight junctions after exposure to (un)sulfated secondary BAs. This is compared to the impact of the dietary fiber pectin with different degrees of methylation (DM) and blockiness (DB), with disruption induced by calcium ionophore A23187 under both normal and hyperglycemic conditions. Unsulfated lithocholic acid (LCA) and deoxycholic acid (DCA) show a stronger rescuing effect, particularly evident under 20 mM glucose levels. DM19 with high DB (HB) and DM43HB pectin exhibit rescuing effects under both glucose conditions. Notably, DM19HB and DM43HB display higher rescue effects under 20 mM glucose compared to 5 mM glucose. The study demonstrates that specific pectins such as DM19HB and DM43HB may serve as alternatives for preventing barrier disruption in the case of disturbed DCA metabolism.
Collapse
Affiliation(s)
- Xin Tang
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands
| | - Xiaochen Chen
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands
| | - Michela Ferrari
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands
| | - Marthe T C Walvoort
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, the Netherlands
| | - Paul de Vos
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands
| |
Collapse
|
|
4
|
Imai M, Hiramoto K, Tanaka S, Ooi K. Interactions between Age-Related Type 2 Diabetes and the Small Intestine. Biol Pharm Bull 2024; 47:791-795. [PMID: 38583950 DOI: 10.1248/bpb.b24-00065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
The number of patients with type 2 diabetes is increasing worldwide. The mechanisms leading to type 2 diabetes and its complications is being researched; however, the pathological mechanisms of diabetes in the small intestine remain unclear. Therefore, we examined these pathological mechanisms in the small intestine using a mouse model of type 2 diabetes (KK-Ay/TaJcl) aged 10 and 50 weeks. The results showed that diabetes worsened with age in the mice with type 2 diabetes. In these mice, advanced glycation end products (AGEs) in the small intestine and mast cell expression increased, whereas diamine oxidase (DAO) decreased; increased tumor necrosis factor (TNF)-α and histamine levels in the plasma and small intestine were also detected. Additionally, the expression of zonula occludens (ZO)-1 and Claudin1 and cell adhesion molecules in the small intestine reduced. These results exacerbated with age. These findings indicate that type 2 diabetes causes AGE/mast cell/histamine and TNF-α signal transmission in the small intestine and decreases small intestinal wall cell adhesion molecules cause TNF-α and histamine to flow into the body, worsening the diabetic condition. In addition, this sequence of events is suggested to be strengthened in aged mice with type 2 diabetes, thus exacerbating the disease. These findings of this study may facilitate the elucidation of the pathological mechanisms of type 2 diabetes and its associated complications.
Collapse
Affiliation(s)
- Masashi Imai
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science
| | - Keiichi Hiramoto
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science
| | - Shota Tanaka
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science
| | - Kazuya Ooi
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science
| |
Collapse
|
|
5
|
Pashayee-Khamene F, Hatami B, Cheraghpour M, Yari Z. Keeping an eye on the nutrition: The importance of nutrition management on cardiometabolic risk factors in cirrhotic patients. Clin Nutr ESPEN 2023; 58:186-192. [PMID: 38057004 DOI: 10.1016/j.clnesp.2023.09.927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 08/26/2023] [Accepted: 09/26/2023] [Indexed: 11/07/2023]
Abstract
Chronic liver diseases, especially cirrhosis, are associated with significant morbidity and mortality. Besides predisposing to chronic liver disease per se, diabetes, hypertension, and dyslipidemia worsen the prognosis of patients with cirrhosis induced by other causes. There is no standard of care in the management of these factors in patients with cirrhosis. Also, in particular, it is not known whether nutritional interventions in the modification of cardiometabolic factors can improve the course of cirrhosis or not. This narrative review aimed to investigate the clinical significance of diabetes, hypertension, and dyslipidemia and appropriate nutritional interventions in cirrhotic patients. A comprehensive literature search of the published data was performed in regard to the association of cirrhosis with cardiometabolic factors and the management of cirrhosis and its complications. There is limited evidence on the association of cirrhosis with cardiometabolic risk factors. Cirrhotic cardiometabolic abnormalities are associated with an increased risk of complications, such that the coexistence of diabetes, hypertension, and dyslipidemia increases the risk of clinical decompensation in cirrhosis. Dietary management of cirrhotic patients with risk factors such as diabetes, hypertension, or dyslipidemia does not seem to be considerably different from non-cirrhotic patients.
Collapse
Affiliation(s)
- Fereshteh Pashayee-Khamene
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zahra Yari
- Department of Nutrition Research, National Nutrition and Food Technology Research Institute and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
6
|
Gairing SJ, Schleicher EM, Labenz C. Diabetes mellitus - risk factor and potential future target for hepatic encephalopathy in patients with liver cirrhosis? Metab Brain Dis 2022; 38:1691-1700. [PMID: 36001211 DOI: 10.1007/s11011-022-01068-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 08/08/2022] [Indexed: 10/15/2022]
Abstract
Hepatic encephalopathy (HE) is one of the major complications of cirrhosis, and its presence is associated with poor survival. Several risk factors for HE are well established, including age, history of HE, portosystemic shunts, or poorer liver function. In recent years, diabetes mellitus (DM) has emerged as another potential risk factor for the development of HE. This may be important for many patients, as the incidence of type 2 DM (T2DM) is increasing worldwide and, consequently, the incidence of NAFLD-related cirrhosis is rising simultaneously. In addition, DM is a critical factor in the progression of other liver diseases, such as alcohol-related liver disease. Thus, the number of patients with cirrhosis and comorbid T2DM will also increase. To date, the prevalence of DM already ranges between 22 - 40% in patients with cirrhosis. DM-associated factors that may influence the risk of HE include systemic inflammation, insulin resistance with increased muscle protein breakdown as well as autonomic dysfunction with prolonged intestinal transit time and small intestinal bacterial overgrowth. Currently, the evidence for an association between DM and both minimal and overt HE is weak and it seems likely that only poor glycemic control has an impact on HE risk. In addition, there are some early signs indicating that DM may impair the response of patients with HE to pharmacological therapies such as rifaximin. Thus, improvements in the management of glycemic control may be a candidate future target to reduce the risk of HE. In this concise review, we summarize the current evidence on the association between DM and HE and its potential future implications.
Collapse
Affiliation(s)
- Simon Johannes Gairing
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg- University, Mainz, Germany
| | - Eva Maria Schleicher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg- University, Mainz, Germany
| | - Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany.
- Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg- University, Mainz, Germany.
| |
Collapse
|
|
7
|
Valder S, Brinkmann C. Exercise for the Diabetic Gut-Potential Health Effects and Underlying Mechanisms. Nutrients 2022; 14:813. [PMID: 35215463 PMCID: PMC8877907 DOI: 10.3390/nu14040813] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/10/2022] [Accepted: 02/12/2022] [Indexed: 02/01/2023] Open
Abstract
It can be assumed that changes in the gut microbiota play a crucial role in the development of type 2 diabetes mellitus (T2DM). It is generally accepted that regular physical activity is beneficial for the prevention and therapy of T2DM. Therefore, this review analyzes the effects of exercise training on the gut microbiota composition and the intestinal barrier function in T2DM. The current literature shows that regular exercise can influence the gut microbiota composition and the intestinal barrier function with ameliorative effects on T2DM. In particular, increases in the number of short-chain fatty acid (SCFA)-producing bacteria and improvements in the gut barrier integrity with reduced endotoxemia seem to be key points for positive interactions between gut health and T2DM, resulting in improvements in low-grade systemic inflammation status and glycemic control. However, not all aspects are known in detail and further studies are needed to further examine the efficacy of different training programs, the role of myokines, SCFA-producing bacteria, and SCFAs in the relevant metabolic pathways. As microbial signatures differ in individuals who respond differently to exercise training programs, one scientific focus could be the development of computer-based methods for the personalized analysis of the gut microbiota in the context of a microbiota/microbiome-based training program.
Collapse
Affiliation(s)
- Sarah Valder
- Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, 50933 Cologne, Germany;
| | - Christian Brinkmann
- Department of Preventive and Rehabilitative Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, 50933 Cologne, Germany
- Department of Fitness & Health, IST University of Applied Sciences, 40233 Dusseldorf, Germany
| |
Collapse
|
|
8
|
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.
Collapse
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
| |
Collapse
|
|
9
|
Gibbons CH, Silvestri NJ. Autonomic Dysfunction in Neuromuscular Disorders. Neuromuscul Disord 2022. [DOI: 10.1016/b978-0-323-71317-7.00005-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
|
|
10
|
Schol J, Wauters L, Dickman R, Drug V, Mulak A, Serra J, Enck P, Tack J. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. Neurogastroenterol Motil 2021; 33:e14237. [PMID: 33939892 DOI: 10.1111/nmo.14237] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 12/28/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
Collapse
Affiliation(s)
- Jolien Schol
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Lucas Wauters
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Ram Dickman
- Division of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikwa, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Vasile Drug
- University of Medicine and Pharmacy Gr T Popa Iasi and University Hospital St Spiridon, Iasi, Romania
| | - Agata Mulak
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland
| | - Jordi Serra
- Digestive System Research Unit. University Hospital Vall d'Hebron. Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd), Barcelona, Spain
| | - Paul Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany
| | - Jan Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | | |
Collapse
|
|
11
|
Schol J, Wauters L, Dickman R, Drug V, Mulak A, Serra J, Enck P, Tack J. United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United European Gastroenterol J 2021; 9:287-306. [PMID: 33939892 PMCID: PMC8259275 DOI: 10.1002/ueg2.12060] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 12/28/2020] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
Collapse
Affiliation(s)
- Jolien Schol
- Department of Gastroenterology and HepatologyUniversity Hospitals LeuvenLeuvenBelgium
| | - Lucas Wauters
- Department of Gastroenterology and HepatologyUniversity Hospitals LeuvenLeuvenBelgium
| | - Ram Dickman
- Division of GastroenterologyRabin Medical CenterBeilinson HospitalPetach TikwaIsrael and Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
| | - Vasile Drug
- University of Medicine and Pharmacy Gr T Popa Iasi and University Hospital St SpiridonIasiRomania
| | - Agata Mulak
- Department of Gastroenterology and HepatologyWroclaw Medical UniversityWroclawPoland
| | - Jordi Serra
- Digestive System Research Unit. University Hospital Vall d'Hebron. Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas (CIBERehd)BarcelonaSpain
| | - Paul Enck
- Department of Internal Medicine VI: Psychosomatic Medicine and PsychotherapyUniversity Hospital TübingenTübingenGermany
| | - Jan Tack
- Department of Gastroenterology and HepatologyUniversity Hospitals LeuvenLeuvenBelgium
| |
Collapse
|
|
12
|
Aziz F, Aberer F, Moser O, Sourij C, von Lewinski D, Kaser S, Reichardt B, Sourij H. Impact of comorbidities on mortality in hospitalized influenza patients with diabetes - Analysis of the Austrian Health Insurance. Diabetes Res Clin Pract 2021; 174:108758. [PMID: 33744375 DOI: 10.1016/j.diabres.2021.108758] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 03/04/2021] [Accepted: 03/09/2021] [Indexed: 01/21/2023]
Abstract
AIMS To assess the impact of characteristics and comorbidities on the hospitalization rate and 30- and 90-days all-cause mortality after hospitalization for influenza-related illness (IRI) in individuals with diabetes. METHODS Data of 507,184 individuals with diabetes enrolled in the national Austrian Health Insurance database during 2013-2017 were analyzed. Hospitalization for IRI was defined as per International Classification of Disease 10 codes (J09, J10, J11). All-cause mortality was calculated for 30- and 90-days post-hospitalization. RESULTS Of the total diabetes population, 1994 (0.4%) were hospitalized for IRI during 2013-2017. The rate of comorbidities was higher in individiuals who were hospitalized due to IRI as compared with the general diabetes population. Overall 30-days cumulative mortality following hospitalization for IRI was 7.9% and 90-days mortality was 10.3%. The risk (adjusted Hazard Ratio, 95% Confidence Interval) of IRI related 90-days mortality increased with age (50-59: 3.00, 0.65-13.94; 60-69: 4.16, 0.99-17.55; 70-79: 4.79, 1.16-19.76; 80+: 7.15, 1.74-29.46), heart failure (1.97, 1.31-2.98), renal disease (1.50, 1.05-2.14), and Charlson comorbidity index (1.14, 1.08-1.19). CONCLUSIONS Older age, heart failure, renal disease, and Charlson comorbidity index were significant predictors of mortality following hospitalization for IRI in individuals with diabetes. These findings could help in improving the clinical management and performance of surveillance and health systems concerning IRI in Austria.
Collapse
Affiliation(s)
- Faisal Aziz
- Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Felix Aberer
- Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria
| | - Othmar Moser
- Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria; Division of Exercise Physiology and Metabolism, University of Bayreuth, Bayreuth, Germany
| | - Caren Sourij
- Division of Cardiology, Medical University of Graz, Graz, Austria
| | | | - Susanne Kaser
- Department for Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Harald Sourij
- Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
| |
Collapse
|
|
13
|
Nyavor Y, Brands CR, Nicholson J, Kuther S, Cox KK, May G, Miller C, Yasuda A, Potter F, Cady J, Heyman HM, Metz TO, Stark TD, Hofmann T, Balemba OB. Supernatants of intestinal luminal contents from mice fed high-fat diet impair intestinal motility by injuring enteric neurons and smooth muscle cells. Neurogastroenterol Motil 2021; 33:e13990. [PMID: 32969549 DOI: 10.1111/nmo.13990] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 08/12/2020] [Accepted: 08/25/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Damage to enteric neurons and impaired gastrointestinal muscle contractions cause motility disorders in 70% of diabetic patients. It is thought that enteric neuropathy and dysmotility occur before overt diabetes, but triggers of these abnormalities are not fully known. We tested the hypothesis that intestinal contents of mice with and without high-fat diet- (HFD-) induced diabetic conditions contain molecules that impair gastrointestinal movements by damaging neurons and disrupting muscle contractions. METHODS Small and large intestinal segments were collected from healthy, standard chow diet (SCD) fed mice. Filtrates of ileocecal contents (ileocecal supernatants; ICS) from HFD or SCD mice were perfused through them. Cultured intact intestinal muscularis externa preparations were used to determine whether ICS and their fractions obtained by solid-phase extraction (SPE) and SPE subfractions collected by high-performance liquid chromatography (HPLC) disrupt muscle contractions by injuring neurons and smooth muscle cells. KEY RESULTS ICS from HFD mice reduced intestinal motility, but those from SCD mice had no effect. ICS, aqueous SPE fractions and two out of twenty HPLC subfractions of aqueous SPE fractions from HFD mice blocked muscle contractions, caused a loss of nitrergic myenteric neurons through inflammation, and reduced smooth muscle excitability. Lipopolysaccharide and palmitate caused a loss of nitrergic myenteric neurons but did not affect muscle contractions. CONCLUSIONS & INFERENCES Unknown molecules in intestinal contents of HFD mice trigger enteric neuropathy and dysmotility. Further studies are required to identify the toxic molecules and their mechanisms of action.
Collapse
Affiliation(s)
- Yvonne Nyavor
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | | | - Jessica Nicholson
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Sydney Kuther
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Kortni K Cox
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - George May
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | | | - Allysha Yasuda
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Forrest Potter
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Joshua Cady
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| | - Heino M Heyman
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Thomas O Metz
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, USA
| | - Timo D Stark
- Lehrstuhl für Lebensmittelchemie und Molekulare Sensorik, Technische Universität München, Freising, Germany
| | - Thomas Hofmann
- Lehrstuhl für Lebensmittelchemie und Molekulare Sensorik, Technische Universität München, Freising, Germany
| | - Onesmo B Balemba
- Department of Biological Sciences, University of Idaho, Moscow, ID, USA
| |
Collapse
|
|
14
|
Labenz C, Nagel M, Kremer WM, Hilscher M, Schilling CA, Toenges G, Kuchen R, Schattenberg JM, Galle PR, Wörns MA. Association between diabetes mellitus and hepatic encephalopathy in patients with cirrhosis. Aliment Pharmacol Ther 2020; 52:527-536. [PMID: 32598080 DOI: 10.1111/apt.15915] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/12/2020] [Accepted: 06/03/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Diabetes mellitus may lead to increased serum ammonia and systemic inflammation thereby promoting hepatic encephalopathy (HE). AIM To investigate the potential association between diabetes mellitus/glycaemic control and the presence of covert HE as well as the development of overt HE in a prospective setting. METHODS A total of 240 patients with liver cirrhosis were included into this prospective cohort study and followed for a median of 17 months. Covert HE was diagnosed by pathological results in the Portosystemic Hepatic Encephalopathy Score. Predictors for the presence of covert HE or the development of overt HE were analysed using logistic regression or Cox-regression models. RESULTS At study inclusion, 65 patients (27.1%) presented with diabetes mellitus and covert HE was detected in 33.3%. Patients with diabetes mellitus had a more preserved liver function as compared to patients without diabetes mellitus (MELD 9 vs 10; P = 0.043). In regression analyses after adjustment for confounders, diabetes mellitus was independently associated with the presence of covert HE at study inclusion and the development of overt HE during follow-up. These associations were confirmed in separate propensity-score-weighted regression models. In subgroup analyses, patients with worse glycaemic control (HbA1c >= 6.5%) had a pronounced risk for covert HE (OR 2.264, 95% CI 1.002-5.118) and overt HE (HR 4.116, 95% CI 1.791-9.459). CONCLUSIONS Diabetes mellitus may associate with higher risk for the presence of covert HE and the development of overt HE in patients with liver cirrhosis. Adequate glycaemic control may be a potential target to attenuate this important complication.
Collapse
Affiliation(s)
- Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Michael Nagel
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Wolfgang M Kremer
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Max Hilscher
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Caroline A Schilling
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Gerrit Toenges
- Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Robert Kuchen
- Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Jörn M Schattenberg
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Metabolic Liver Research Program, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| | - Marcus-Alexander Wörns
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.,Cirrhosis Center Mainz (CCM), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
| |
Collapse
|
|
15
|
Sodium-glucose co-transporter (SGLT) inhibitor restores lost axonal varicosities of the myenteric plexus in a mouse model of high-fat diet-induced obesity. Sci Rep 2020; 10:12372. [PMID: 32704004 PMCID: PMC7378553 DOI: 10.1038/s41598-020-69256-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 07/08/2020] [Indexed: 01/19/2023] Open
Abstract
Diabetes impairs enteric nervous system functions; however, ultrastructural changes underlying the pathophysiology of the myenteric plexus and the effects of sodium-glucose co-transporter (SGLT) inhibitors are poorly understood. This study aimed to investigate three-dimensional ultrastructural changes in axonal varicosities in the myenteric plexus and the effect thereon of the SGLT inhibitor phlorizin in mice fed a high-fat diet (HFD). Three-dimensional ultrastructural analysis using serial block-face imaging revealed that non-treated HFD-fed mice had fewer axonal varicosities and synaptic vesicles in the myenteric plexus than did normal diet-fed control mice. Furthermore, mitochondrial volume was increased and lysosome number decreased in the axons of non-treated HFD-fed mice when compared to those of control mice. Phlorizin treatment restored the axonal varicosities and organelles in HFD-fed mice. Although HFD did not affect the immunolocalisation of PGP9.5, it reduced synaptophysin immunostaining in the myenteric plexus, which was restored by phlorizin treatment. These results suggest that impairment of the axonal varicosities and their synaptic vesicles underlies the damage to the enteric neurons caused by HFD feeding. SGLT inhibitor treatment could restore axonal varicosities and organelles, which may lead to improved gastrointestinal functions in HFD-induced obesity as well as diabetes.
Collapse
|
|
16
|
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.
Collapse
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.
| |
Collapse
|
|
17
|
Nyavor Y, Estill R, Edwards H, Ogden H, Heideman K, Starks K, Miller C, May G, Flesch L, McMillan J, Gericke M, Forney L, Balemba O. Intestinal nerve cell injury occurs prior to insulin resistance in female mice ingesting a high-fat diet. Cell Tissue Res 2019; 376:325-340. [PMID: 30778729 DOI: 10.1007/s00441-019-03002-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 01/30/2019] [Indexed: 12/11/2022]
Abstract
Diabetic patients suffer from gastrointestinal disorders associated with dysmotility, enteric neuropathy and dysbiosis of gut microbiota; however, gender differences are not fully known. Previous studies have shown that a high-fat diet (HFD) causes type two diabetes (T2D) in male mice after 4-8 weeks but only does so in female mice after 16 weeks. This study seeks to determine whether sex influences the development of intestinal dysmotility, enteric neuropathy and dysbiosis in mice fed HFD. We fed 8-week-old C57BL6 male and female mice a standard chow diet (SCD) or a 72% kcal HFD for 8 weeks. We analyzed the associations between sex and intestinal dysmotility, neuropathy and dysbiosis using motility assays, immunohistochemistry and next-generation sequencing. HFD ingestion caused obesity, glucose intolerance and insulin resistance in male but not female mice. However, HFD ingestion slowed intestinal propulsive motility in both male and female mice. This was associated with decreased inhibitory neuromuscular transmission, loss of myenteric inhibitory motor neurons and axonal swelling and loss of cytoskeletal filaments. HFD induced dysbiosis and changed the abundance of specific bacteria, especially Allobaculum, Bifidobacterium and Lactobacillus, which correlated with dysmotility and neuropathy. Female mice had higher immunoreactivity and numbers of myenteric inhibitory motor neurons, matching larger amplitudes of inhibitory junction potentials. This study suggests that sex influences the development of HFD-induced metabolic syndrome but dysmotility, neuropathy and dysbiosis occur independent of sex and prior to T2D conditions. Gastrointestinal dysmotility, neuropathy and dysbiosis might play a crucial role in the pathophysiology of T2D in humans irrespective of sex.
Collapse
Affiliation(s)
- Yvonne Nyavor
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Rachel Estill
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Hannah Edwards
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Hailey Ogden
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Kaila Heideman
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Kiefer Starks
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Christopher Miller
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - George May
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Lance Flesch
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - John McMillan
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Martin Gericke
- Institute for Anatomy, University of Leipzig, Liebigstraße 13, 04103, Leipzig, Germany
| | - Larry Forney
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA
| | - Onesmo Balemba
- Department of Biological Sciences, University of Idaho, 875 Perimeter Drive, LSS 252, Moscow, ID, 83844, USA.
| |
Collapse
|
|
18
|
Abstract
OBJECTIVE To investigate the relation of Hashimoto's thyroiditis (HT) to cholelithiasis and cholecystectomy in a retrospective population-based study. SETTING Cohort study. PARTICIPANTS We identified 1268 patients aged ≥20 years with HT between 2000 and 2010 as the study cohort. PRIMARY AND SECONDARY OUTCOME MEASURES Patients without HT were randomly selected from a database and propensity-matched with the study cohort at a 1:4 ratio according to age, sex, comorbidities and year of the index date to measure the incidence of cholelithiasis and cholecystectomy. RESULTS The cumulative incidence of cholelithiasis was higher in the HT cohort than that in the non-HT cohort (log-rank test, p<0.001), with a 1.91-fold higher risk of choleithiasis (95% CI 1.58 to 2.33) after adjustment for comorbidities. The age-specific relative risk of cholelithiasis in the HT cohort was higher than that in the non-HT cohort for patients aged ≥50 years (adjusted HR (aHR)=2.59, 95% CI 1.33 to 5.03). The sex-specific relative risk of cholelithiasis in the HT cohort was higher than that in the non-HT cohort for women (aHR=1.99, 95% CI 1.63 to 2.44). Compared with those in the non-HT cohort, patients with HT without (aHR=1.95, 95% CI 1.53 to 2.49) and with (aHR=1.94, 95% CI 1.51 to 2.49) thyroxine treatment were associated with a higher risk of cholelithiasis. Compared with those in the non-HT cohort, patients with HT had a higher risk of cholecystectomy (aHR=1.28, 95% CI 1.02 to 1.61). CONCLUSIONS Inability to obtain information on several potential confounding factors and misclassification of important covariates are the major limitations of the study. Our study indicates HT per se was associated with the development of cholelithiasis, which has been validated by the association between cholecystectomy and HT. Surveys and health education on cholelithiasis in women aged ≥50 years with HT should be considered by clinicians, and further prospective research should be done on this topic.
Collapse
Affiliation(s)
- Chien-Hua Chen
- Digestive Disease Center, Show Chwan Memorial Hospital, Changhua, Taiwan
- Digestive Disease Center, Changbing Show-Chwan Memorial Hospital, Changhua County, Taiwan
- Department of Food Science and Technology, Hungkuang University, Taichung, Taiwan
- Chung Chou University of Science and Technology, Changhua County, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan
| |
Collapse
|
|
19
|
Higenamine inhibits apoptosis and maintains survival of gastric smooth muscle cells in diabetic gastroparesis rat model via activating the β2-AR/PI3K/AKT pathway. Biomed Pharmacother 2017; 95:1710-1717. [DOI: 10.1016/j.biopha.2017.08.112] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Revised: 08/24/2017] [Accepted: 08/24/2017] [Indexed: 12/11/2022] Open
|
|
20
|
Yue SJ, Liu J, Feng WW, Zhang FL, Chen JX, Xin LT, Peng C, Guan HS, Wang CY, Yan D. System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus. Front Pharmacol 2017; 8:694. [PMID: 29051733 PMCID: PMC5633780 DOI: 10.3389/fphar.2017.00694] [Citation(s) in RCA: 105] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 09/19/2017] [Indexed: 01/02/2023] Open
Abstract
The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.
Collapse
Affiliation(s)
- Shi-Jun Yue
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Key Laboratory of Marine Drugs (Ministry of Education of China), School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.,Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Juan Liu
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wu-Wen Feng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fei-Long Zhang
- Information Center, Beijing University of Chinese Medicine, Beijing, China
| | - Jian-Xin Chen
- Information Center, Beijing University of Chinese Medicine, Beijing, China
| | - Lan-Ting Xin
- Key Laboratory of Marine Drugs (Ministry of Education of China), School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.,Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Cheng Peng
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hua-Shi Guan
- Key Laboratory of Marine Drugs (Ministry of Education of China), School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.,Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Chang-Yun Wang
- Key Laboratory of Marine Drugs (Ministry of Education of China), School of Medicine and Pharmacy, Ocean University of China, Qingdao, China.,Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Dan Yan
- Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
21
|
Büyükçoban S, Akan M, Koca U, Eğlen MY, Çiçeklioğlu M, Mavioğlu Ö. Comparison of Two Different Enteral Nutrition Protocol in Critically Ill Patients. Turk J Anaesthesiol Reanim 2016; 44:265-269. [PMID: 27909608 DOI: 10.5152/tjar.2016.92499] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 09/06/2016] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE In this study, two enteral nutrition protocols with different gastric residual volumes (GRVs) and different monitoring intervals were compared with respect to gastrointestinal intolerance findings in intensive care unit (ICU) patients. METHODS The study was carried out prospectively in 60 patients in the anaesthesiology and reanimation ICU under mechanical ventilation support, who were scheduled to take enteral feeding. Patients were sequentially divided into two groups: Group 1, GRV threshold of 100 mL, and monitoring interval of 4 hours, and Group 2, GRV threshold of 200 mL, monitoring interval of 8 hours. To test the significant difference between the groups, Student's t test, chi-square text and Fisher exact test were used. RESULTS In Group 1, 3.3% vomiting, 6.6% diarrhoea was observed; in Group 2, 16.6% vomiting, 10% diarrhoea. In terms of total intolerance (vomiting and/or diarrhoea) of the two groups, the incidence was significantly higher in Group 2 (33.3%) than in Group 1 (10%) (p=0.02). CONCLUSION According to the results of the study, a lower gastrointestinal intolerance rate was detected in the GRV threshold 100 mL, monitoring interval for 4 hours protocol (Group 1) than in GRV threshold 200 mL, monitoring interval for 8 hours protocol (Group 2); Group 1 may be preferred renovation.
Collapse
Affiliation(s)
- Sibel Büyükçoban
- Department of Anaestesiology and Reanimation, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Mert Akan
- Department of Anaestesiology and Reanimation, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | - Uğur Koca
- Department of Anaestesiology and Reanimation, Dokuz Eylül University School of Medicine, İzmir, Turkey
| | | | - Meltem Çiçeklioğlu
- Department of Public Health, Ege University School of Medicine, İzmir, Turkey
| | - Ömür Mavioğlu
- Department of Anaestesiology and Reanimation, Dokuz Eylül University School of Medicine, İzmir, Turkey
| |
Collapse
|
|
22
|
Crimmins S, Smiley R, Preston K, Yau A, Mccallum R, Ali MS. Increased Expression of Pyloric ERβ Is Associated With Diabetic Gastroparesis in Streptozotocin-Induced Male Diabetic Rats. Gastroenterology Res 2016; 9:39-46. [PMID: 27785323 PMCID: PMC5040542 DOI: 10.14740/gr701w] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/15/2016] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastroparesis is a significant co-morbidity affecting up to 50% of patients with diabetes and is disproportionately found in women. Prior studies have suggested that loss of interstitial cells of Cajal, hyperglycemia, and nitric oxide dysfunction are potential causes of gastroparesis. Since diabetic gastroparesis affects more women than men, we performed an exploratory study with a diabetic rat model to determine if sex hormone signaling is altered in those where gastroparesis develops. METHODS We injected male rats with streptozotocin (STZ) to model type I diabetes, as confirmed by blood glucose levels. Gastroparesis was determined by acetaminophen gavage and serum acetaminophen levels. Rats were grouped based on acetaminophen and blood glucose data: diabetic (DM), diabetic and gastroparetic (DM + GP), and control (CM). Serum levels of testosterone, estrogen, and insulin were determined as well as aromatase expression in pyloric tissue and serum. Androgen receptor and estrogen receptor α (ERα) and β (ERβ) were also measured in the pylorus. RESULTS Compared to CM, estrogen increased and testosterone decreased in both DM and DM + GP rats. Sex hormone levels were not different between DM and DM + GP. Serum aromatase was increased in DM and DM + GP rats; however, pyloric tissue levels were not significantly different from controls. ERα was unchanged and androgen receptor decreased in DM and DM + GP. ERβ was increased only in DM + GP animals. CONCLUSION Our study implicates increased pyloric ERβ in the development of gastroparesis in STZ-induced male diabetic rats. Increased serum aromatase is likely responsible for altered sex hormone levels. Our study supports the implication of sex hormone signaling in diabetic development and demonstrates a potential unique role for pyloric ERβ in male diabetic gastroparesis.
Collapse
Affiliation(s)
- Stephen Crimmins
- Department of Clinical Investigation, William Beaumont Army Medical Center, 5005 N. Piedras Street, El Paso, TX 79920-5001, USA
- These authors contributed equally to first authorship of this manuscript
| | - Rebecca Smiley
- Department of Clinical Investigation, William Beaumont Army Medical Center, 5005 N. Piedras Street, El Paso, TX 79920-5001, USA
- These authors contributed equally to first authorship of this manuscript
| | - Kerry Preston
- Department of Clinical Investigation, William Beaumont Army Medical Center, 5005 N. Piedras Street, El Paso, TX 79920-5001, USA
| | - Amy Yau
- Internal Medicine Clinic, San Antonio Military Medical Center, 3551 Roger Brooke Dr., San Antonio, TX 78219, USA
| | - Richard Mccallum
- Department of Internal Medicine, Texas Tech Health Science Center Paul L. Foster School of Medicine, 4800 Alberta Ave, El Paso, TX 79905-2709, USA
| | - Mohammed Showkat Ali
- Department of Clinical Investigation, William Beaumont Army Medical Center, 5005 N. Piedras Street, El Paso, TX 79920-5001, USA
| |
Collapse
|
|
23
|
Whitehead K, Cortes Y, Eirmann L. Gastrointestinal dysmotility disorders in critically ill dogs and cats. J Vet Emerg Crit Care (San Antonio) 2016; 26:234-53. [PMID: 26822390 DOI: 10.1111/vec.12449] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Revised: 07/21/2015] [Accepted: 08/30/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To review the human and veterinary literature regarding gastrointestinal (GI) dysmotility disorders in respect to pathogenesis, patient risk factors, and treatment options in critically ill dogs and cats. ETIOLOGY GI dysmotility is a common sequela of critical illness in people and small animals. The most common GI motility disorders in critically ill people and small animals include esophageal dysmotility, delayed gastric emptying, functional intestinal obstruction (ie, ileus), and colonic motility abnormalities. Medical conditions associated with the highest risk of GI dysmotility include mechanical ventilation, sepsis, shock, trauma, systemic inflammatory response syndrome, and multiple organ failure. The incidence and pathophysiology of GI dysmotility in critically ill small animals is incompletely understood. DIAGNOSIS A presumptive diagnosis of GI dysmotility is often made in high-risk patient populations following detection of persistent regurgitation, vomiting, lack of tolerance of enteral nutrition, abdominal pain, and constipation. Definitive diagnosis is established via radioscintigraphy; however, this diagnostic tool is not readily available and is difficult to perform on small animals. Other diagnostic modalities that have been evaluated include abdominal ultrasonography, radiographic contrast, and tracer studies. THERAPY Therapy is centered at optimizing GI perfusion, enhancement of GI motility, and early enteral nutrition. Pharmacological interventions are instituted to promote gastric emptying and effective intestinal motility and prevention of complications. Promotility agents, including ranitidine/nizatidine, metoclopramide, erythromycin, and cisapride are the mainstays of therapy in small animals. PROGNOSIS The development of complications related to GI dysmotility (eg, gastroesophageal reflux and aspiration) have been associated with increased mortality risk. Institution of prophylaxic therapy is recommended in high-risk patients, however, no consensus exists regarding optimal timing of initiating prophylaxic measures, preference of treatment, or duration of therapy. The prognosis for affected small animal patients remains unknown.
Collapse
Affiliation(s)
- KimMi Whitehead
- Emergency and Critical Care Department, Oradell Animal Hospital, Paramus, NJ, 07452
| | - Yonaira Cortes
- Emergency and Critical Care Department, Oradell Animal Hospital, Paramus, NJ, 07452
| | - Laura Eirmann
- the Nutrition Department (Eirmann), Oradell Animal Hospital, Paramus, NJ, 07452
| |
Collapse
|
|
24
|
|
|
25
|
Zhang Y, Jeon M, Rich LJ, Hong H, Geng J, Zhang Y, Shi S, Barnhart TE, Alexandridis P, Huizinga JD, Seshadri M, Cai W, Kim C, Lovell JF. Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines. NATURE NANOTECHNOLOGY 2014; 9:631-8. [PMID: 24997526 PMCID: PMC4130353 DOI: 10.1038/nnano.2014.130] [Citation(s) in RCA: 316] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Accepted: 06/02/2014] [Indexed: 04/14/2023]
Abstract
There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and provide good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ∼ 20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1,000). Unlike conventional chromophores, nanonaps exhibit non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole-body imaging.
Collapse
Affiliation(s)
- Yumiao Zhang
- Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, USA
- Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, USA
| | - Mansik Jeon
- Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, USA
- Department of Creative IT Engineering, POSTECH, Pohang, Korea
| | - Laurie J. Rich
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, USA
| | - Hao Hong
- Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, USA
| | - Jumin Geng
- Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, USA
| | - Yin Zhang
- Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, USA
| | - Sixiang Shi
- Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, USA
| | - Todd E. Barnhart
- Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, USA
| | - Paschalis Alexandridis
- Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, USA
| | - Jan D. Huizinga
- Farncombe Family Digestive Health Research Institute, Department of Enterology, McMaster University, Hamilton, Canada
| | - Mukund Seshadri
- Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, USA
| | - Weibo Cai
- Department of Radiology and Department of Medical Physics, University of Wisconsin, Madison, USA
- Correspondence and requests for materials should be addressed to W.C. (nuclear imaging), C.K. (photoacoustics) and J.F.L. (general inquiries)
| | - Chulhong Kim
- Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, USA
- Department of Creative IT Engineering, POSTECH, Pohang, Korea
- Correspondence and requests for materials should be addressed to W.C. (nuclear imaging), C.K. (photoacoustics) and J.F.L. (general inquiries)
| | - Jonathan F. Lovell
- Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, USA
- Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, USA
- Correspondence and requests for materials should be addressed to W.C. (nuclear imaging), C.K. (photoacoustics) and J.F.L. (general inquiries)
| |
Collapse
|
|
26
|
Wei T, Tian W, Xie G. Non-esterified fatty acids induce apoptosis via a ROS-dependent mechanism involving the mitochondrial pathway in bovine abomasal smooth muscle cells. EUR J LIPID SCI TECH 2014. [DOI: 10.1002/ejlt.201400137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Teng Wei
- College of Veterinary Medicine; Jilin University; Changchun Jilin China
| | - Wulin Tian
- College of Veterinary Medicine; Jilin University; Changchun Jilin China
| | - Guanghong Xie
- College of Veterinary Medicine; Jilin University; Changchun Jilin China
| |
Collapse
|
|
27
|
Weerakoon HTW, Ranasinghe JGS, Navaratna A, Sivakanesan R, Galketiya KB, Rosairo S. Can the type of gallstones be predicted with known possible risk factors?: A comparison between mixed cholesterol and black pigment stones. BMC Gastroenterol 2014; 14:88. [PMID: 24884475 PMCID: PMC4017087 DOI: 10.1186/1471-230x-14-88] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pathogenesis of gallstones (GS) is multifactorial and multiple genetic and environmental factors have been identified in different populations for different types of GS with varying prevalence. However the role of the each aetiological factor on the formation of mixed cholesterol and black pigment GS has not being addressed adequately. Hence in this study we attempted to compare known possible risk factors for mixed cholesterol and black pigment GS among two groups of patients with two types of GS. METHODS The study was done on a cohort of patients with symptomatic GS admitted to the Teaching Hospital Peradeniya, Sri Lanka over a period of 18 months. Clinical and epidemiological data and physical parameters of the patients were recorded and surgically removed GS were analyzed chemically and physically to identify the type of GS. In addition lipid profile was done in all the patients with normal serum bilirubin levels. RESULTS A total of 86 patients were included in the study. Mixed cholesterol GS was significantly common among females than males (χ2 test, p = 0.029). Mixed cholesterol GS was commonly seen among patients belonging to Moor ethnicity (χ2 test, p = 0.009). Majority of patients with mixed cholesterol GS had body mass index above 25 kg/m2 (χ2 test, p = 0.018). Black pigment GS were significantly common among patients with type II diabetes mellitus (Fisher's exact test, p = 0.035). Further all the patients with chronic haemolytic anaemia and alcoholic cirrhosis had black pigment GS. Age, family history, Fasting Blood Glucose, dyslipidaemia, lipid profile, parity and use of oral contraceptive pills in females, smoking and alcohol intake in males did not differ significantly among patients in the two groups. CONCLUSION Gender, ethnicity and body mass index can be used to predict the formation of mixed cholesterol GS and black pigment GS.
Collapse
Affiliation(s)
- Harshi TW Weerakoon
- Department of Biochemistry, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, Sri Lanka
| | | | - Ayanthi Navaratna
- Department of Chemistry, Faculty of Science, University of Peradeniya, Peradeniya, Sri Lanka
| | - Ramaiah Sivakanesan
- Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Kuda B Galketiya
- Department of Surgery, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Shanthini Rosairo
- Department of Surgery, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| |
Collapse
|
|
28
|
Butt Z, Jadoon NA, Salaria ON, Mushtaq K, Riaz IB, Shahzad A, Hashmi AM, Sarwar S. Diabetes mellitus and decompensated cirrhosis: risk of hepatic encephalopathy in different age groups. J Diabetes 2013; 5:449-55. [PMID: 23731902 DOI: 10.1111/1753-0407.12067] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2012] [Revised: 04/26/2013] [Accepted: 05/28/2013] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The aim of the present study was to examine the association of diabetes mellitus (DM) with the prevalence and severity of hepatic encephalopathy (HE) in patients with decompensated cirrhosis (DC) and determine the impact of age and gender on this relationship. METHODS West Haven criteria was used to prospectively evaluate 352 consecutive patients with DC for the presence of HE. Detailed clinicobiochemical profiling of patients was performed. Categorical data and ordered categorical variables were evaluated using the Chi-squared test for independence and trend, respectively. Continuous normal and non-parametric data were evaluated using the t-test and Mann-Whitney U-test, respectively. RESULTS At the time of admission, HE was present in 50.3% of patients. In all, 118 patients had DM (33.5%). Patients with DM had a significantly higher prevalence (58.5% vs 42.6%; P = 0.03) and severity of HE (P(trend) = 0.01) than patients without DM. However, there were no significant differences between the two groups in terms of Child-Pugh class, MELD scores, the presence of ascites and esophageal varices. Patients with DM had higher platelet counts than those without DM (P(trend) = 0.003). In age and gender subgroup analyses, older patients and men with DM had significantly greater evidence of HE (P = 0.02 and 0.03, respectively). Multivariate analysis showed that DM (P = 0.03) and older age (P = 0.006) were independently related to HE, whereas the association of gender was non-significant. CONCLUSION Both DM and older age are independently associated with HE in patients with cirrhosis.
Collapse
Affiliation(s)
- Zeeshan Butt
- Mayo Hospital, King Edward Medical University, Lahore, Pakistan; Center for Biomedical Research, Lahore, Pakistan
| | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Xu L, Qu Z, Guo F, Pang M, Gao S, Zhu H, Gu F, Sun X. Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats. Peptides 2013; 48:137-46. [PMID: 23965296 DOI: 10.1016/j.peptides.2013.08.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 08/08/2013] [Accepted: 08/08/2013] [Indexed: 02/08/2023]
Abstract
This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes.
Collapse
Affiliation(s)
- Luo Xu
- Department of Pathophysiology, Medical College of Qingdao University, Qingdao 266021, China.
| | | | | | | | | | | | | | | |
Collapse
|
|
30
|
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
| |
Collapse
|
|
31
|
Urita Y, Noda T, Watanabe D, Iwashita S, Hamada K, Sugimoto M. Effects of a soybean nutrition bar on the postprandial blood glucose and lipid levels in patients with diabetes mellitus. Int J Food Sci Nutr 2012; 63:921-9. [DOI: 10.3109/09637486.2012.694847] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
|
|
32
|
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.
Collapse
Affiliation(s)
- Sun Joo Kim
- Department of Physiology, Keimyung University School of Medicine, Daegu, Korea
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Bouchoucha M, Uzzan B, Cohen R. Metformin and digestive disorders. DIABETES & METABOLISM 2011; 37:90-6. [DOI: 10.1016/j.diabet.2010.11.002] [Citation(s) in RCA: 86] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2010] [Revised: 10/22/2010] [Accepted: 11/03/2010] [Indexed: 12/22/2022]
|
|
34
|
Larssen L, Medhus AW, Hauge T. Treatment of malignant gastric outlet obstruction with stents: an evaluation of the reported variables for clinical outcome. BMC Gastroenterol 2009; 9:45. [PMID: 19534803 PMCID: PMC2708180 DOI: 10.1186/1471-230x-9-45] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2008] [Accepted: 06/17/2009] [Indexed: 12/19/2022] Open
Abstract
Background Malignant gastric outlet obstruction (GOO) is commonly seen in patients with advanced gastric-, pancreatic-, duodenal, hepatobiliary or metastatic malignancies. Ten to 25% of patients with pancreatic cancer will develop duodenal obstruction during the course of the disease. Duodenal stenting with self-expandable metal stents is an alternative treatment to surgical bypass procedures. Our aim was to review the published literature regarding treatment of malignant GOO with stents to reveal whether the information provided is sufficient to evaluate the clinical effects of this treatment Methods A literature search from 2000 – 2007 was conducted in Pub Med, Embase, and Cochrane library, combining the following search terms: duodenal stent, malignant duodenal obstruction, gastric outlet obstruction, SEMS, and gastroenteroanastomosis. All publications presenting data with ≥ 15 patients and only articles written in English were included and a review focusing on the following parameters were conducted: 1) The use of graded scoring systems evaluating clinical success; 2) Assessment of Quality of life (QoL) before and after treatment; 3) Information on stent-patency; 4) The use of objective criteria to evaluate the stent effect. Results 41 original papers in English were found; no RCT's. 16 out of 41 studies used some sort of graded scoring system. No studies had objectively evaluated QoL before or after stent treatment, using standardized QoL-questionnaires, 32/41 studies reported on stent patency and 9/41 performed an oral contrast examination after stent placement. Objective quantitative tests of gastric emptying had not been performed. Conclusion Available reports do not provide sufficient relevant information of the clinical outcome of duodenal stenting. In future studies, these relevant issues should be addressed to allow improved evaluation of the effect of stent treatment.
Collapse
Affiliation(s)
- Lene Larssen
- Department of Gastroenterology, Oslo University Hospital, Ullevaal, Department of Gastroenterology, Kirkeveien 166, N-0407 Oslo, Norway.
| | | | | |
Collapse
|
|
35
|
Schmidt PT, Abrahamsson H, Dolk A, Hausken T, Karling P, Lindberg G, Nyhlin H, Ohlsson B, Simrèn M, Sjölund K, Stotzer PO, Törnblom H. Methods to assess gastric motility and sensation. Scand J Gastroenterol 2009; 43:1285-95. [PMID: 18618332 DOI: 10.1080/00365520802240263] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Peter Thelin Schmidt
- Karolinska Institutet, Department of Medicine, Karolinska University Hospital, Stockholm, Solna, Sweden.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Kalaitzakis E, Olsson R, Henfridsson P, Hugosson I, Bengtsson M, Jalan R, Björnsson E. Malnutrition and diabetes mellitus are related to hepatic encephalopathy in patients with liver cirrhosis. Liver Int 2007; 27:1194-201. [PMID: 17919230 DOI: 10.1111/j.1478-3231.2007.01562.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS Studies on animal models of hepatic encephalopathy (HE) suggest that poor nutritional status may facilitate the development of HE. Insulin resistance and diabetes mellitus have recently been reported to affect cognition in patients with hepatitis C cirrhosis awaiting liver transplantation. Our aim was to investigate the effects of malnutrition and diabetes mellitus on HE in unselected patients with liver cirrhosis. METHODS A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of HE according to the West-Haven criteria as well as by means of two psychometric tests and fasting plasma ammonium ion concentrations. Nutritional status was assessed by anthropometry and estimation of recent weight change. Fasting plasma glucose was measured, and in a subgroup of 84 patients fasting serum insulin and insulin resistance were also determined. RESULTS Fifty-one (40%) cirrhotics were malnourished, 33 (26%) had diabetes and 42 (34%) had HE. Patients with vs. without malnutrition had more frequently HE (46 vs. 27%; P=0.031) but did not differ in age, aetiology or severity of liver cirrhosis (P>0.1). Multivariate analysis showed that the time needed to perform number connection test A was independently correlated to age, the Child-Pugh score, diabetes and malnutrition (P<0.05 for all). Plasma ammonium ion levels were related to insulin resistance (r=0.42, P<0.001) and muscle mass (r=0.28, P=0.003). CONCLUSION Malnutrition and diabetes mellitus seem to be related to HE in patients with liver cirrhosis. Nutritional status and insulin resistance might be implicated in the pathogenesis of HE.
Collapse
Affiliation(s)
- Evangelos Kalaitzakis
- Section of Gastroenterology and Hepatology, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | | | | | | | | | | | | |
Collapse
|
|
37
|
Medhus AW, Bjørnland K, Emblem R, Husebye E. Liquid and solid gastric emptying in adults treated for Hirschsprung's disease during early childhood. Scand J Gastroenterol 2007; 42:34-40. [PMID: 17190760 DOI: 10.1080/00365520600842211] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Dysmotility of the upper gastrointestinal tract has been reported in children with Hirschsprung's disease. In the present study, gastric emptying was studied in adult patients with Hirschsprung's disease to elucidate whether there is a persisting involvement of the upper gastrointestinal tract in this group of patients. MATERIAL AND METHODS Gastric emptying of caloric liquids and solids was studied in 16 adult patients with surgically treated Hirschsprung's disease during early childhood and in age-matched controls. To examine liquid emptying, the paracetamol absorption test was applied using a meal containing glucose, lactose, maize oil, water (2020 kJ) and paracetamol. To examine solid emptying, the 13C gastric emptying breath test was applied using a meal containing white bread, margarine, a one-egg omelette (1050 kJ) and [13C]-octanoic acid. Gastrointestinal symptoms were recorded according to a standardized questionnaire. RESULTS For liquid meal emptying, the time until emptying commenced was 8.1+/-1.9 and 2.9+/-0.9 min (mean+/-SE) in patients and controls, respectively (p=0.02). Thereafter, the first 25% of the meal emptied in 6.8+/-0.8 and 12.1+/-1.1 min in patients and controls, respectively (p=0.0005). The overall emptying rate tended to be delayed in patients compared with controls (p=0.06). For the solid meal, a delay in emptying was evident (p=0.02). The patients reported more symptoms from the upper gastrointestinal tract than the controls, but the symptoms were not significantly related to the emptying pathology demonstrated. CONCLUSIONS The present study demonstrates that adult patients with Hirschsprung's disease have an abnormal pattern of gastric emptying, indicating persisting involvement of the upper gastrointestinal tract.
Collapse
Affiliation(s)
- Asle W Medhus
- Department of Medicine, Ullevål University Hospital, Oslo, Norway.
| | | | | | | |
Collapse
|
|
38
|
Gibson TM, Cotter MA, Cameron NE. Effects of poly(ADP-ribose) polymerase inhibition on dysfunction of non-adrenergic non-cholinergic neurotransmission in gastric fundus in diabetic rats. Nitric Oxide 2006; 15:344-50. [PMID: 16644248 DOI: 10.1016/j.niox.2006.03.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2005] [Revised: 03/15/2006] [Accepted: 03/17/2006] [Indexed: 02/02/2023]
Abstract
Diabetes mellitus compromises nitric oxide (NO)-mediated endothelium-dependent relaxation of blood vessels, which has been linked to the excessive generation of reactive oxygen species. There are also deleterious effect on nitrergic innervation, contributing to autonomic neuropathy symptoms such as impotence and gastroporesis. Poly(ADP-ribose) polymerase (PARP) is a nuclear protein stimulated by DNA damage, caused, for example, by oxidative stress. Activation has been linked to impaired endothelial nitric oxide synthase (eNOS)-mediated vasodilation in experimental diabetes. There is no information on the potential role of PARP in nitrergic nerve dysfunction, therefore, the aim was to examine the effects of PARP inhibition, using 3-aminobenzamide (3-AB) on neurally mediated gastric fundus relaxation in streptozotocin-induced diabetic rats. Eight weeks of diabetes caused a 42.5% deficit in maximum relaxation of in vitro gastric fundus strips to electrical stimulation of the non-adrenergic non-cholinergic innervation. This was largely prevented or corrected (4 weeks of treatment following 4 weeks of untreated diabetes) by 3-AB. Diabetes also markedly attenuated the maintenance of relaxation responses to prolonged stimulation, and this was partially corrected by 3-AB treatment. Experiments in the presence of the NOS inhibitor, N(G)-nitro-L-arginine, and/or blockade of the co-transmitter, vasoactive intestinal polypeptide, by alpha-chymotrypsin, showed that the beneficial effects of 3-AB were primarily due to improved nitrergic neurotransmission. Thus, PARP plays an important role in defective nitrergic neurotransmission in experimental diabetes, which may have therapeutic implications for treatment of aspects of diabetic autonomic neuropathy.
Collapse
Affiliation(s)
- T Michael Gibson
- School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK
| | | | | |
Collapse
|
|
39
|
Han SH, White S, Patel K, Dutson E, Gracia C, Mehran A. Acute gastric remnant dilation after laparoscopic Roux-en-Y gastric bypass operation in long-standing type I diabetic patient: Case report and literature review. Surg Obes Relat Dis 2006; 2:664-6. [PMID: 16979957 DOI: 10.1016/j.soard.2006.08.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2006] [Revised: 07/09/2006] [Accepted: 08/05/2006] [Indexed: 11/20/2022]
Affiliation(s)
- Soo Hwa Han
- Section of Minimally Invasive and Bariatric Surgery, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-6904, USA
| | | | | | | | | | | |
Collapse
|
|
40
|
Sigal SH, Stanca CM, Kontorinis N, Bodian C, Ryan E. Diabetes mellitus is associated with hepatic encephalopathy in patients with HCV cirrhosis. Am J Gastroenterol 2006; 101:1490-6. [PMID: 16863551 DOI: 10.1111/j.1572-0241.2006.00649.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES An increased ammonia level of gut bacterial origin is an important mediator in the pathogenesis of hepatic encephalopathy (HE), and constipation is a frequent precipitant of hepatic coma. Because diabetes mellitus (DM) may be associated with delayed gastrointestinal transit, we speculated that its presence in patients with HCV-related cirrhosis would predispose to and exacerbate HE. METHODS Sixty-five patients (50 men, 15 women) with HCV-related cirrhosis attending a liver transplantation clinic were assessed for severity of liver disease and presence of DM in a cross-sectional study. A modified Child-Pugh score that excluded HE was calculated. Frequency and severity of HE (absent, mild, and severe) in diabetic and nondiabetic patients were assessed. Clinical severity of cirrhosis and results of neuropsychometric testing in diabetic and nondiabetic patients with mild and severe HE were compared. RESULTS Fifty-four patients (83%) had HE (33 mild, 21 severe). Twenty patients (31%) had DM. HE was present in 19 (95%) patients with diabetes and 35 (78%) patients without diabetes (p = 0.087). Severity of HE was greater in diabetic (35% mild, 60% severe) than in nondiabetic patients (58% mild, 20% severe) (p = 0.007). In both the mild and severe HE categories, severity of liver disease in diabetic patients was otherwise milder than in the nondiabetic patients. CONCLUSIONS Diabetic patients with HCV cirrhosis have more severe HE. Diabetic patients have severe HE at earlier stages of biochemical decompensation and portal hypertension compared with nondiabetic patients.
Collapse
Affiliation(s)
- Samuel H Sigal
- Center for Liver Disease and Transplantation, New York Weill Cornell Medical Center, New York 10021, USA
| | | | | | | | | |
Collapse
|
|
41
|
Urita Y, Ishihara S, Akimoto T, Kato H, Hara N, Honda Y, Nagai Y, Nakanishi K, Shimada N, Sugimoto M, Miki K. Seventy-five gram glucose tolerance test to assess carbohydrate malabsorption and small bowel bacterial overgrowth. World J Gastroenterol 2006; 12:3092-5. [PMID: 16718794 PMCID: PMC4124388 DOI: 10.3748/wjg.v12.i19.3092] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate non-invasively the incidence of absorption of carbohydrates in diabetic patients during an oral glucose tolerance test (OGTT) and to determine whether malabsorption may be associated with insulin secretion and insulin resistance.
METHODS: A standard 75-g OGTT was performed in 82 diabetic patients. The patients received 75 g of anhydrous glucose in 225 mL of water after an overnight fasting and breath samples were collected at baseline and up to 120 min after ingestion. Breath hydrogen and methane concentrations were measured. Blood glucose and serum insulin concentrations were measured before ingestion and at 30, 60, 90, 120 min post-ingestion.
RESULTS: When carbohydrate malabsorption was defined as subjects with an increase of at least 10 ppm (parts per million) in hydrogen or methane excretion within a 2-h period, 28 (34%) had carbohydrate malabsorption. According to the result of increased breath test, 21 (75%) patients were classified as small bowel bacterial overgrowth and 7 (25%) as glucose malabsorption. Patients with carbohydrate malabsorption were older and had poor glycemic control as compared with those without carbohydrate malabsorption. The HOMA value, the sum of serum insulin during the test and the Δinsulin/Δglucose ratio were greater in patients with carbohydrate malabsorption.
CONCLUSION: Insulin resistance may be overestimated by using these markers if the patient has carbohydrate malabsorption, or that carbohydrate malabsorption may be present prior to the development of insulin resistance. Hence carbohydrate malabsorption should be taken into account for estimating insulin resistance and β-cell function.
Collapse
Affiliation(s)
- Yoshihisa Urita
- Department of General Medicine and Emergency Care, Toho University School of Medicine, Omori Hospital, Ota-Ku, Tokyo 143-8541, Japan.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Huang EY, Wang CJ, Hsu HC, Sun LM. Characteristics and predictive factors of early-onset diarrhoea during pelvic irradiation. Br J Radiol 2006; 79:419-24. [PMID: 16632623 DOI: 10.1259/bjr/51376226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
This study reported characteristics and predictive factors of early-onset diarrhoea in patients receiving pelvic irradiation. We retrospectively reviewed 229 patients undergoing radiotherapy alone for cervical or uterine cancer. Oral barium was taken 90 min before simulation. According to contrast medium within small intestine only or colon in simulation films, we categorised patients as normal and rapid transit groups. Small or large volume of small-bowel was also evaluated according to barium distribution of simulation films. Whole-pelvic irradiation (39.6-45 Gy/22-25 fractions) was delivered to all patients initially. We recorded the onset of diarrhoea during pelvic irradiation. The rates of early-onset diarrhoea (<10 Gy) were compared between these two groups. The incidence of diarrhoea before 10 Gy was 7% and 17% (p = 0.138) in patients with normal and rapid transit, respectively. In multivariate analysis, interaction among rapid transit, prior abdomen operation and large small-bowel volume (p = 0.019) were noted for early-onset diarrhoea. Further subgroup analysis revealed that rapid transit (p = 0.046) was a significant factor in patients with both prior abdominal operation and large small-bowel volume. The incidence of early-onset diarrhoea was as high as 40% in this particular group. Patients experiencing early-onset diarrhoea had a higher incidence of moderate to severe diarrhoea (65%) than those without early-onset diarrhoea (23%) (p<0.001). In multivariate analysis, early-onset diarrhoea was the only factor of moderate to severe diarrhoea (p = 0.001). In conclusion, rapid small-bowel transit may be predisposed to early-onset diarrhoea during pelvic radiotherapy in patients with both prior abdominal operations and large small-bowel volume. Early-onset diarrhoea is considered as a predictive factor of diarrhoea of a higher grade.
Collapse
Affiliation(s)
- E Y Huang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan
| | | | | | | |
Collapse
|
|
43
|
Abstract
Autonomic disorders may present in a varied fashion. Symptoms that may require treatment include orthostatic intolerance, gastrointestinal distress, sudomotor abnormalities, and urologic and sexual dysfunction. Realistic treatment goals should be outlined for patients, with the expectations that symptoms can be improved, but that the disease is unlikely to be cured and long-term therapy may be required. Orthostatic intolerance is usually treated by a combination of pharmacologic and nonpharmacologic therapies. Nonpharmacologic therapies include compression stockings, adequate fluid and salt intake, and lifestyle modifications. Polypharmacologic therapy is often the standard and can include a volume-expanding agent (such as fludrocortisone) and a sympathomimetic agent. This combination will improve symptoms dramatically in most patients. Treatment of gastrointestinal disorders should address the particular symptom involved: gastroparesis, constipation, or diarrhea. Treatment of sexual and urogenital dysfunction often requires a combination of pharmacologic intervention and lifestyle modifications for peak effectiveness. Patient education is the cornerstone of treatment in any of the autonomic disorders. Given enough education and motivation, many patients will be able to participate in their treatment, which will provide a feeling of empowerment and control over a disease that is often frustratingly resistant to treatment.
Collapse
Affiliation(s)
- Christopher H Gibbons
- Autonomic and Peripheral Nerve Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA 02215, USA
| | | |
Collapse
|
|
44
|
Reddy PMK, Dkhar SA, Subramanian R. Effect of insulin on small intestinal transit in normal mice is independent of blood glucose level. BMC Pharmacol 2006; 6:4. [PMID: 16448577 PMCID: PMC1444921 DOI: 10.1186/1471-2210-6-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2005] [Accepted: 02/01/2006] [Indexed: 11/28/2022] Open
Abstract
Background Insulin is the drug of choice in the management of diabetes mellitus (DM). About 76 % of diabetic patients suffer from gastrointestinal (GI) disorders. Therapy of DM with insulin primarily involves lowering of elevated blood glucose levels. Hence, on any organ in addition to insulin's effect, hypoglycaemic effect also prevails. A systematic study exploring the effect of insulin on small intestinal transit in normal laboratory animals is lacking. Hence, in the present study, the possible effect of insulin with or without associated hypoglycaemia on small intestinal transit in normal mice was examined. Results Insulin in all the doses tested (2 μ, 2 m and 2 U/kg) elicited a significant acceleration of SIT. The lower doses of insulin (2 μ and 2 m U/kg) produced significant acceleration of SIT and were associated with normal blood glucose levels. However, the highest dose of insulin (2 U/kg) produced an acceleration of SIT that was associated with significant fall in blood glucose levels. Further, the 2 m and 2 U doses of insulin significantly elevated serum insulin and C-peptide levels. Conclusion Insulin at the lowest dose produced an acceleratory effect on SIT that was independent of blood glucose and serum insulin levels in normal mice.
Collapse
Affiliation(s)
| | - Steven Aibor Dkhar
- Department of Pharmacology, JIPMER, Pondicherry-605006, India
- Department of Pharmacology, AVMC, Pondicherry-605006, India
| | - Ramaswamy Subramanian
- Department of Pharmacology, JIPMER, Pondicherry-605006, India
- Department of Pharmacology, AVMC, Pondicherry-605006, India
| |
Collapse
|
|
45
|
Fregonesi CEPT, Molinari SL, Alves AMP, Defani MA, Zanoni JN, Bazotte RB, de Miranda Neto MH. Morphoquantitative aspects of nitrergic myoenteric neurons from the stomach of diabetic rats supplemented with acetyl-L-carnitine. Anat Histol Embryol 2005; 34:93-7. [PMID: 15771670 DOI: 10.1111/j.1439-0264.2004.00578.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The NADPH-diaphorase (NADPH-d) positive myoenteric neurons from the body of the stomach of rats with streptozotocin-induced diabetes with or without supplementation with acetyl-L-carnitine (ALC) were evaluated. At the age of 105 days the animals were divided into four groups: normoglycaemic (C), normoglycaemic supplemented with ALC (CC), diabetic (D) and diabetic supplemented with ALC (DC). The supplementation with ALC (200 mg/kg body weight/day) to groups CC and DC was made during 105 days. After this period the animals were killed and the stomach removed and subjected to the histochemical technique of NADPH-d for the staining of the neurons of the myoenteric plexus. The area of 500 neurons of each group was investigated, as well as the neuronal density in an area of 23.84 mm(2) in each stomach. ALC promoted reduction (P < 0.05) of fasting glycaemia, water ingestion and areas of the profiles of the cell bodies of the NADPH-d neurons in the diabetic animals. The density of these neurons was not statistically different in the groups studied. It is suggested, therefore, a moderate neuroprotective effect of ALC, because the diminishment of the areas of the neuronal profiles in the supplemented diabetic animals, although being statistically significant relative to the non-supplemented diabetics, was not sufficient to equal the values from the non-diabetic controls.
Collapse
Affiliation(s)
- C E P T Fregonesi
- Department of Physiotherapy, Sciences Technology Faculty - Paulista State University (FCT/UNESP), Campus of Presidente Prudente, SP, Brazil.
| | | | | | | | | | | | | |
Collapse
|
|
46
|
Kalinowski CPH, Kirsch JR. Strategies for prophylaxis and treatment for aspiration. Best Pract Res Clin Anaesthesiol 2004; 18:719-37. [PMID: 15460555 DOI: 10.1016/j.bpa.2004.05.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The absolute incidence of aspiration is difficult to define because of its relatively low occurrence and difficulty in diagnosis. The gastric volume predisposing to aspiration is larger than 30 ml. Fasting times for fluids have reduced; however, a large meal may require 9 hours of preoperative fasting. Preoperative carbohydrate-enriched beverages may attenuate postoperative catabolism. Aspiration occurs most frequently during induction and laryngoscopy. Awake fibre-optic intubation may be a suitable alternative in high-risk cases for aspiration. The role of cricoid pressure in anaesthesia needs re-evaluation as radiological and clinical evidence suggest that it may be ineffective and may impede intubation and ventilation. Chemoprophylaxis does not reduce the severity of aspiration pneumonitis as gastric bile is unaffected by these agents and induces a worse pneumonitis than gastric acid. Patients may be discharged home 2 hours after aspirating provided they are clinically unaffected and have postoperative surveillance.
Collapse
Affiliation(s)
- Christopher Peter Henry Kalinowski
- The Department of Anesthesia and Peri-Operative Medicine, 3181 SW Sam Jackson Park Road, Oregon Health and Sciences University, Portland, OR 97239, USA.
| | | |
Collapse
|
|
47
|
Rajeswaran C, Dawson A, Bonney G, Oxynos C, Nicholson VL, Gilbey SG. Intussusception as a gastrointestinal complication of diabetes: case report and literature review. THE BRITISH JOURNAL OF DIABETES & VASCULAR DISEASE 2004; 4:408-413. [DOI: 10.1177/14746514040040060801] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
This is the first reported case of intussusception in a patient with type 1 diabetes mellitus complicated by gastroparesis and autonomic neuropathy. Literature on the reported cases of intussusception in patients with diabetes, its aetiopathology and possible association with gastroparesis has been systematically reviewed following a Medline database search (1951 to June 2003) Intussusception should be considered in the differential diagnosis of gastrointestinal symptoms in diabetic patients presenting with hyperglycaemia.
Collapse
Affiliation(s)
| | - Alison Dawson
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Glen Bonney
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | - Costas Oxynos
- St James's University Hospital, Beckett Street, Leeds, LS9 7TF, UK
| | | | | |
Collapse
|
|
48
|
Kennedy WR. Chapter 2 Unmyelinated nerves, challenges, and opportunities: skin biopsy and beyond. ACTA ACUST UNITED AC 2004; 57:8-14. [PMID: 16106601 DOI: 10.1016/s1567-424x(09)70338-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Affiliation(s)
- William R Kennedy
- Department of Neurology, University of Minnesota, MMC 187, 420 Delaware St. SE, Minneapolis, MI 55455, USA.
| |
Collapse
|
|
49
|
Abstract
Autonomic neuropathy affects every system in the body including the eye, cardiovascular, respiratory, and gastrointestinal and neurovascular systems. The diagnosis confers an attenuated life expectancy, but much can be done to alleviate symptoms and to address the underlying disorder.
Collapse
Affiliation(s)
- Aaron I Vinik
- Strelitz Diabetes Research Institutes, Departments of Internal Medicine and Anatomy/Neurobiology, Eastern Virginia Medical School, Norfolk, Va., USA
| | | |
Collapse
|
|
50
|
Abstract
OBJECTIVE Erythromycin is a motilin agonist that greatly increases the fractional rate of gastric emptying. Although a number of studies document the efficacy of erythromycin in improving gastric emptying, little information exists concerning symptom improvement in patients with gastroparesis. The aim of this study was to review clinical trials of erythromycin to determine the efficacy of this agent in producing symptom relief in patients with gastroparesis. METHODS A MEDLINE search from 1966 to 2001 was performed to identify all clinical trials using erythromycin in patients with gastroparesis. The search was further limited to clinical trials using symptom assessment as an endpoint. References from index citations were reviewed to identify additional studies. The search was conducted independently by two authors, and discrepancies were resolved by consensus opinion. RESULTS Thirty-five clinical trials were identified, and five met inclusion criteria. One study each involved gastroparesis caused by surgery and systemic sclerosis. Three studies evaluated patients with diabetic or idiopathic gastroparesis. No study used symptoms as a primary endpoint. Improvement was reported in 26 of 60 (43%) patients. Individual symptom scores were available for 23 of 60 subjects in these studies, and symptom improvement was seen in 11 of 23 (48%) patients. One study compared erythromycin and metoclopromide in an open-label, crossover fashion, and found no difference between the two agents. All studies were methodologically weak and highly subject to bias. Four of five studies were open-label trials. Sample sizes in all studies were < or =13 subjects, and treatment duration was < or =4 wk in all studies. CONCLUSIONS Although clearly a potent prokinetic, limited data exist concerning efficacy of erythromycin in treating gastroparesis. Small sample sizes, uncontrolled designs, short duration, and inadequate symptom assessment limit available studies. Well-designed trials designed to assess symptom relief in gastroparesis are needed.
Collapse
Affiliation(s)
- Kalyani Maganti
- Department of Internal Medicine, St. Joseph's Hospital, Chicago, Illinois, USA
| | | | | |
Collapse
|