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Diabetic gastroenteropathy:An underdiagnosed complication

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World Journal of Diabetes 2021年第6期12卷 794-809页

作者： Marcio JoséConcepción Zavaleta Jhean Gabriel Gonzáles Yovera Diego Martín Moreno Marreros Luciana del Pilar Rafael Robles Kely Roxana Palomino Taype Karen Nohelly Soto Gálvez Luis Fernando Arriola Torres Julia Cristina Coronado Arroyo Luis Alberto Concepción Urteaga Division of Endocrinology Hospital Nacional Guillermo Almenara IrigoyenLima 12590Peru Division of Gastroenterology Hospital Nacional Guillermo Almenara IrigoyenLima 12590Peru Division of Medicine Universidad Nacional de TrujilloTrujillo 13011Peru Division of Endocrinology Hospital Nacional Dos de MayoLima 150101Peru Division of Endocrinology Instituto de Neurología y Endocrinología AvanzadaAndahuaylas 03700Peru Clinical Management Unit Hospital Nacional Guillermo Almenara IrigoyenLima 12590Peru Division of Neurology Instituto de Neurología y Endocrinología AvanzadaAndahuaylas 03700Peru Division of Obstetrics and Gynaecology Clínica VesalioLima 15036Peru Division of Neumology Hospital Regional Docente de TrujilloTrujillo 13011Peru

This article is an extensive review that provides an update on the pathophysiology,symptoms,diagnosis,and treatment of diabetic gastroenteropathy.There is no reported prevalence,but it has been described that patients with type 1 diabetes have a cumulative incidence at 10 years of 5.2%,and type 2 patients,1%.Also,in the group of type 1 diabetes,it has been observed that women are more likely to present this condition(5.8%vs 3.5%).Many factors are associate with its development(e.g.,hyperglycemia,vagal dysfunction,loss of expression of neural nitric oxide synthase in the myenteric plexus,alterations in the Cajal interstitial cell network,and oxidative stress).Gastrointestinal discomfort could be perceived 70% higher in diabetic patients,describing that 25%of diabetic patients experience gastrointestinal symptoms.Diabetic enteropathy could affect any portion of the gastrointestinal tract,but esophageal alterations were described in more than 60% of diabetic patients,also 60% of them present constipation,and 20%,diarrhea.Gastric emptying scintigraphy is useful to evaluate gastroparesis,therefore,gastric retention of more than 60%at 2 h has a sensitivity of 100% and specificity of 20% for diagnosis;however,other studies such as breath tests,with a sensitivity of 89% and a specificity of 80%,or the endoscopic capsule contribute to the diagnosis.There is no cure;however,management must be multidisciplinary,focused on slowing the progression of diabetic gastroenteropathy,reducing symptoms,and restoring function;that includes nutritional recommendation,maintain glucose levels kept below 180 mg/dL,use of prokinetics,anti-emetics;nowadays,it has been special interest in surgical treatment,such as pyloroplasty,also gastric electrical stimulation appears to be another alternative.

关键词： Gastroenteropathy gastroparesis Diabetes mellitus Complication Gastrointestinal disease Treatment

Gastrointestinal complications of diabetes mellitus

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World Journal of Diabetes 2013年第3期4卷 51-63页

作者： Babu Krishnan Shithu Babu Jessica Walker Adrian B Walker Joseph M Pappachan Department of Gastroenterology University College HospitalLondon NW1 2BUUnited Kingdom Department of Medicine Watford General HospitalLondon WD18 0HBUnited Kingdom University of Newcastle Newcastle upon Tyne NE1 7RUUnited Kingdom Department of Endocrinology University Hospital of North Staffordshire NHS TrustStoke-on-Trent ST4 6QGUnited Kingdom

Diabetes mellitus affects virtually every organ system in the body and the degree of organ involvement depends on the duration and severity of the disease,and other co-morbidities.Gastrointestinal(GI) involvement can present with esophageal dysmotility,gastro-esophageal reflux disease(GERD),gastroparesis,enteropathy,non alcoholic fatty liver disease(NAFLD) and glycogenic hepatopathy.Severity of GERD is inversely related to glycemic control and management is with prokinetics and proton pump inhibitors.Diabetic gastroparesis manifests as early satiety,bloating,vomiting,abdominal pain and erratic glycemic control.Gastric emptying scintigraphy is considered the gold standard test for diagnosis.Management includes dietary modifications,maintaining euglycemia,prokinetics,endoscopic and surgical treatments.Diabetic enteropathy is also common and management involves glycemic control and symptomatic measures.NAFLD is considered a hepatic manifestation of metabolic syndrome and treatment ismainly lifestyle measures,with diabetes and dyslipidemia management when coexistent.Glycogenic hepatopathy is a manifestation of poorly controlled type 1 diabetes and is managed by prompt insulin treatment.Though GI complications of diabetes are relatively common,awareness about its manifestations and treatment options are low among physicians.Optimal management of GI complications is important for appropriate metabolic control of diabetes and improvement in quality of life of the patient.This review is an update on the GI complications of diabetes,their pathophysiology,diagnostic evaluation and management.

关键词： Gastrointestinal complications Diabetes mellitus Esophageal complications Nonalcoholic fatty liver disease Diabetic gastroparesis Diabetic enteropathy Glycogenic hepatopathy

Predisposing factors for positive D-Xylose breath test for evaluation of small intestinal bacterial overgrowth:A retrospective study of 932 patients

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World Journal of Gastroenterology 2015年第15期21卷 4574-4582页

作者： Richard A Schatz Qing Zhang Nilesh Lodhia Jonathan Shuster Phillip P Toskes Baharak Moshiree Department of Medicine Medical University of South Carolina Department of Gastroenterology University of Florida Gainesville Department of Gastroenterology Medical University of South Carolina Charleston Department of Health Outcomes and Policy University of Florida Gainesville Department of Gastroenterology University of Miami

AIM: To investigate, in the largest cohort to date, patient characteristics and associated risk factors for developing small intestinal bacterial overgrowth(SIBO) using the D-Xylose breath test(XBT).METHODS: We performed a retrospective crosssectional study to analyze patient characteristics who underwent the XBT for evaluation of SIBO. Diagnostic testing with the XBT was performed based on a clinical suspicion for SIBO in patients with symptoms of bloating, abdominal pain, abdominal distension, weight loss, diarrhea, and/or constipation. Consecutive electronicmedical records of 932 patients who completed the XBT at the University of Florida between 2005 and 2009 were reviewed. A two-way Analysis of Variance(ANOVA) was used to test for several associations including age, gender, and body mass index(BMI) with a +XBT. A two-way ANOVA was also performed to control for the differences and interaction with age and between genders. A similar analysis was repeated for BMI. Associations between medical conditions and prior surgical histories were conducted using the Mantel-Haenszel method for 2 by 2 contingency tables, stratified for gender. Reported odds ratio estimates reflect the odds of the prevalence of a condition within the +XBT group to that of the-XBT group. P values of less than 0.05(two-sided) were considered statistically significant.RESULTS: In the 932 consecutive eligible subjects studied, 513 had a positive XBT. A positive association was found between female gender and a positive XBT(P = 0.0025), and females with a positive test were, on average, greater than 5 years older than those with a negative test(P = 0.024). The mean BMI of positive XBT subjects was normal(24.5) and significantly lower than the subjects with a negative XBT(29.5)(P = 0.0050). A positive XBT was associated with gastroesophageal reflux disease(GERD)(OR = 1.35; 95%CI: 1.02-1.80, P = 0.04), peptic ulcer disease(PUD)(OR = 2.61; 95%CI: 1.48-4.59, P gastroparesis(GP)(OR = 2.04; 95%CI: 1.21-3.41, P < 0.01) and steroid use(OR = 1.3

关键词： Intestine Small Irritable bowel syndrome Xylose Breath tests Proton pump inhibitors gastroparesis Bacteria

ER stress and ER stress-induced apoptosis are activated in gastric SMCs in diabetic rats

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World Journal of Gastroenterology 2014年第25期20卷 8260-8267页

作者： Xia Chen Xiang-Sheng Fu Chang-Ping Li Hong-Xian Zhao Department of Gastroenterology Affiliated Hospital of Luzhou Medical College Department of Histology and Embryology Lu-zhou Medical College

AIM: To investigate the gastric muscle injury caused by endoplasmic reticulum(ER) stress in rats with diabetic gastroparesis.METHODS: Forty rats were randomly divided into two groups: a control group and a diabetic group. Diabetes was induced by intraperitoneal injection of 60 mg/kg of streptozotocin. Gastric emptying was determined at the 4th and 12th week. The ultrastructural changes in gastric smooth muscle cells(SMCs) were investigated by transmission electron microscopy. TdT-mediated dUTP nick end labeling(TUNEL) assay was performed to assess apoptosis of SMCs. Expression of the ER stress marker, glucose-regulated protein 78(GRP78),and the ER-specific apoptosis mediator, caspase-12protein, was determined by immunohistochemistry.RESULTS: Gastric emptying was significantly lower in the diabetic rats than in the control rats at the 12th wk(40.71% ± 2.50%, control rats vs 54.65% ± 5.22%, diabetic rats; P gastroparesis.

关键词： Diabetic gastroparesis Apoptosis Endoplasmic retic

Gastric nNOS reduction accompanied by natriuretic peptides signaling pathway upregulation in diabetic mice

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World Journal of Gastroenterology 2014年第16期20卷 4626-4635页

作者： Hong-Li Lu Xu Huang Yi-Song Wu Chun-Mei Zhang Xiang-Min Meng Dong-Hai Liu Young-chul Kim Wen-Xie Xu Department of Physiology Shanghai Jiaotong University School of Medicine Department of Physiology Chungbuk National University College of MedicineChungbuk 361-763South Korea

AIM:To investigate the relationship between neuronal nitric oxide synthase(nNOS)expression and the natriuretic peptide signaling pathway in the gastric fundus of streptozotocin(STZ)-induced diabetic mice.METHODS:Diabetic mice were induced by injection of STZ solution.Immunofluorescence labeling of HuC/D,nNOS and natriuretic peptide receptor-A,B,C(NPRs)in the gastric fundus(GF)was used to observe nNOS expression and whether NPRs exist on enteric neurons.The expression levels of nNOS and NPRs in the diabetic GF were examined by western blotting.An isometric force transducer recorded the electric field stimulation(EFS)-induced relaxation and contraction in the diabetic GF.An intracellular recording method assessed EFSinduced inhibitory junction potentials(IJP)on the GF.GF smooth muscles acquired from normal mice were incubated with different concentrations of the NPRs agonist C-type natriuretic peptide(CNP)for 24 h,after which their nNOS expressions were detected by western blotting.RESULTS:Eight weeks after injection,43 diabetic mice were obtained from mouse models injected with STZ.Immunofluorescence indicated that the number of NOS neurons was significantly decreased and that nNOS expression was significantly downregulated in the diabetic GF.The results of physiological and electrophysiological assays showed that the EFS-induced relaxation that mainly caused by NO was significantly reduced,while the contraction was enhanced in the diabetic GF.EFSinduced IJP showed that L-NAME sensitive IJP in the diabetic GF was significantly reduced compared with control mice.However,both NPR-A and NPR-B were detected on enteric neurons,and their expression levels were upregulated in the diabetic GF.The nNOS expression level was downregulated dose-dependently in GF smooth muscle tissues exposed to CNP.CONCLUSION:These findings suggested that upregulation of the NPs signaling pathway may be involved in GF neuropathy caused by diabetes by decreasing nNOS expression.

关键词： Diabetic gastroparesis Natriuretic peptides Nitric

Gut dysfunction in Parkinson's disease

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World Journal of Gastroenterology 2016年第25期22卷 5742-5752页

作者： Adreesh Mukherjee Atanu Biswas Shyamal Kumar Das Department of Neurology Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research

Early involvement of gut is observed in Parkinson's disease(PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and nonpharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.

关键词： Parkinson’s disease Gut dysfunction Sialorrhea Dysphagia gastroparesis Constipation Gut microbiota

Video capsule endoscopy and CT enterography in diagnosing adult hypertrophic pyloric stenosis

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World Journal of Gastroenterology 2013年第37期19卷 6292-6295页

作者： Grigoriy E Gurvits Amy Tan Dmitri Volkov Department of Gastroenterology New York University School of Medicine/Langone Medical Center Department of Medicine New York University School of Medicine Department of Anesthesiology New York University School of Medicine/Langone Medical Center

Primary adult hypertrophic pyloric stenosis is a rare but important cause of gastric outlet obstruction that may be misdiagnosed as idiopathic gastroparesis.Clinically,patients present with early satiety,abdominal fullness,nausea,epigastric discomfort and eructation.Permanent gastric retention of a video capsule endoscope is diagnostic in differentiating between the two diseases,in the absence of an organic gastric outlet obstruction.This case presents the longest video capsule retention in the medical literature to date.It is also the first case report of adult hypertrophic pyloric stenosis diagnosed with video capsule endoscopy or a computed tomography scan.Finally,an unusual"plugging"of the gastric outlet with free floating capsule has an augmented effect on disease physiology and on patient’s symptoms.

关键词： Video capsule endoscopy Hypertrophic pyloric stenosis gastroparesis Endoscopy Computed tomography enterography

功能性消化不良和胃轻瘫的病理生理学和治疗新进展

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中华消化杂志 2021年第1期41卷 3-15页

作者：陈建德成家飞密歇根大学医学院消化科美国密西根州安娜堡市江苏省中医院消化科南京210029

Functional dyspepsia(FD)and gastroparesis are two common functional gastrointestinal diseases,affecting millions of people in both China and around the world.However,treatment options are limited and difficult due to multiple factors involved in their pathophysiologies.Therefore it is critically important to assess and understand pathophysiologies of these diseases before a treatment is given.In this minireview we provide updates on recent development in the pathophysiologies and treatments of FD and gastroparesis.In addition to common abnormalities in gastric accommodation,antral hypomotility and visceral hypersensitivity,FD has recently been reported to display a number of impairment in duodenal functions,such as low-grade inflammation and increased permeability.For gastroparesis,macrophages have recently been reported to play an important role in its pathophysiology.A brief overview on the assessment of pathophysiologies of FD and gastroparesis is also provided;pros and cons of clinically available methodologies as well as emerging methods are discussed.Finally,available treatment options for FD and gastroparesis are presented in this minireview,including authors′opinions on the advantages and disadvantages of each therapy.Potential novel therapies for FD and gastroparesis,especially those associated with Traditional Chinese Medicine,are also introduced and discussed.

关键词： Functional dyspepsia gastroparesis Gastrointestinal motility Neuromodulation Alternative medicine

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ENDOCRINOLOGY

China Medical Abstracts(Internal Medicine) 1998年第4期15卷 199-202页