Enteric neuropathy in diabetes: Implications for gastrointestinal function.

Diabetes, commonly known for its metabolic effects, also critically affects the enteric nervous system (ENS), which is essential in regulating gastrointestinal (GI) motility, secretion, and absorption. The development of diabetes-induced enteric neuropathy can lead to various GI dysfunctions, such as gastroparesis and irregular bowel habits, primarily due to disruptions in the function of neuronal and glial cells within the ENS, as well as oxidative stress and inflammation. This editorial explores the pathophysiological mechanisms underlying the development of enteric neuropathy in diabetic patients. Additionally, it discusses the latest advances in diagnostic approaches, emphasizing the need for early detection and intervention to mitigate GI complications in diabetic individuals. The editorial also reviews current and emerging therapeutic strategies, focusing on pharmacological treatments, dietary management, and potential neuromodulatory interventions. Ultimately, this editorial highlights the necessity of a multidisciplinary approach in managing enteric neuropathy in diabetes, aiming to enhance patient quality of life and address a frequently overlooked complication of this widespread disease.

Gastroparesis for the nongastroenterologist.

Gastroparesis is a heterogeneous motility disorder characterized by nausea, vomiting, and postprandial fullness. Its diagnosis requires objective documentation of delayed gastric emptying of solid food and exclusion of mechanical obstruction. Its epidemiology is unclear, and the main causes are diabetes mellitus and idiopathic disease. Cardinal symptoms often co-occur. Management involves nutritional assessment, dietary changes, drug evaluation, glycemic control (for patients with diabetes mellitus), and symptom relief. In this review, we explore challenges nongastroenterologists may encounter and how they can use current recommendations to manage patients with gastroparesis.

The influence of delayed gastric emptying on quality of life after partial duodenopancreatectomy.

PURPOSE: Quality of life (QoL) is temporarily compromised after pancreatic surgery, but no evidence for a negative impact of postoperative complications on QoL has been provided thus far. Delayed gastric emptying (DGE) is one of the most common complications after pancreatic surgery and is associated with a high level of distress. Therefore, the aim of this study was to analyse the influence of DGE on QoL. METHODS: This single-centre retrospective study analysed QoL after partial duodenopancreatectomy (PD) via the European Organization for Research and Treatment of Cancer core questionnaire (QLQ-C30). The QoL of patients with and without postoperative DGE was compared. RESULTS: Between 2010 and 2022, 251 patients were included, 85 of whom developed DGE (34%). Within the first postoperative year, compared to patients without DGE, those with DGE had a significantly reduced QoL, by 9.0 points (95% CI: -13.0 to -5.1, p < 0.001). Specifically, physical and psychosocial functioning (p = 0.020) decreased significantly, and patients with DGE suffered significantly more from fatigue (p = 0.010) and appetite loss (p = 0.017) than patients without DGE. After the first postoperative year, there were no significant differences in QoL or symptom scores between patients with DGE and those without DGE. CONCLUSION: Patients who developed DGE reported a significantly reduced QoL and reduced physical and psychosocial functioning within the first year after partial pancreatoduodenectomy compared to patients without DGE.

[Diabetic gastroparesis and type 1 diabetes]. / Gastroparésie diabétique et diabète de type 1.

Gastroparesis is a rare and late microvascular complication, but a significant one of diabetes. Defined by a slowing of gastric emptying, this condition manifests with nonspecific gastrointestinal symptoms, including nausea, vomiting, abdominal pain, postprandial fullness, and early satiety. Faced with such a clinical presentation, it is often challenging to diagnose gastroparesis. In this article, we discuss the diagnostic procedures, as well as therapeutic approaches and management of the disease.

La gastroparésie est une complication microvasculaire rare et tardive, mais conséquente, du diabète. Définie par un ralentissement de la vidange gastrique, cette pathologie se présente sous la forme de symptômes gastro-intestinaux aspécifiques incluant des nausées, des vomissements, des douleurs abdominales, une sensation de réplétion postprandiale et une satiété précoce. Face à une présentation clinique de ce type, il est souvent difficile de poser le diagnostic de gastroparésie. Dans cet article, nous évoquons donc les examens complémentaires permettant de poser le diagnostic, ainsi que les propositions thérapeutiques et la prise en charge de la maladie.

Resolution of severe gastroparesis induced by parasympathetic surge following facial trauma: a case report.

BACKGROUND: Gastroparesis is a condition that affects the motility of the gastrointestinal (GI) tract, causing a delay in the emptying process and leading to nausea, vomiting, bloating, and upper abdominal pain. Motility treatment along with symptom management can be done using antiemetics or prokinetics. This study highlights the diagnostic and therapeutic challenges of gastroparesis and suggests a potential link between facial trauma and symptom remission, indicating the need for further investigation. CASE PRESENTATION: A 46-year-old Hispanic man with hypertension, type 2 diabetes (T2D), and hyperlipidemia on amlodipine 10 mg, lisinopril 5 mg, empagliflozin 25 mg, and insulin glargine presented with a diabetic foot ulcer with probable osteomyelitis. During hospitalization, the patient developed severe nausea and vomiting. The gastroenterology team advised continuing antiemetic medicine and trying very small sips of clear liquids. However, the patient didn't improve. Therefore, the gastroenterology team was contacted again. They advised having stomach emptying tests to rule out gastroparesis as the source of emesis. In addition, they recommended continuing metoclopramide, and starting erythromycin due to inadequate improvement. Studies found a 748-min stomach emptying time. Normal is 45-90 min. An uneventful upper GI scope was done. Severe gastroparesis was verified, and the gastroenterology team advised a percutaneous jejunostomy or gastric pacemaker for gastroparesis. Unfortunately, the patient suffered a mechanical fall resulting in facial trauma. After the fall, the patient's nausea eased, and emesis stopped. He passed an oral liquids trial after discontinuation of erythromycin and metoclopramide. CONCLUSION: This case exemplifies the difficulties in diagnosing and treating gastroparesis. An interesting correlation between parasympathetic surges and recovery in gastroparesis may be suggested by the surprising remission of symptoms following face injuries.

Difference in Cyclic Versus Non-cyclic Symptom Patterns in Patients with the Symptoms of Gastroparesis Undergoing Bioelectric Therapy.

INTRODUCTION: Patients with gastroparesis (Gp) have symptoms with or without a cyclic pattern. This retrospective study evaluates differences in cyclic vs. non-cyclic symptoms of Gp by analyzing mucosal electrogastrogram (mEG), familial dysautonomias, and response to gastric stimulation. METHODS: 37 patients with drug refractory Gp, 7 male and 30 female, with a mean age of 41.4 years, were studied. 18 had diabetes mellitus, 25 had cyclic (Cyc), and 12 had a non-cyclic (NoCyc) pattern of symptoms. Patients underwent temporary mucosal gastric stimulator (tGES) placement, which was done as a trial before permanent stimulator (GES) placement. Electrogastrogram (EGG) by mucosal (mEG) measures, including frequency, amplitude, and frequency-amplitude ratio (FAR), were pre- and post-tGES. Patients' history of personal and familial dysautonomias, quality of life, and symptom scores were recorded. Baseline vs. follow-ups were compared by paired t tests and McNemar's tests. T tests contrasted symptom scores, gastric emptying tests (GET), and mEG measures, while chi-squared tests deciphered comorbidity differences between two groups and univariate and multivariate analyses. RESULTS: There were significantly more patients with diabetes in the Cyc group vs. the NoCyc group. Using a 1 point in symptom outcome, 18 patients did not improve and 19 did improve with tGES. Using univariable analysis, with the cyclic pattern as a predictor, patients exhibiting a cyclic pattern had an odds ratio of 0.22 (95% CI 0.05-0.81, p = 0.054) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The mucosal electrogastrogram frequency to amplitude ratio (FAR) for the "not Improved" group was 19.6 [3.5, 33.6], whereas, for the "Improved" group, it was 54.3 [25.6, 72.5] with a p-value of 0.049. For multivariate logistic regression, accounting for sex and age squared, patients exhibiting a cyclic pattern had an adjusted odds ratio (OR) of 0.16 (95% CI 0.03-0.81, p = 0.027) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The two groups had no significant differences in the personal or inherited history of investigated familial patterns. CONCLUSION: This study shows differences in Gp patients with Cyc vs. NoCyc symptoms in several areas. Larger studies are needed to elicit further differences between the two groups about cycles of symptoms, EGG, findings, familial patterns, and response to mucosal GES.

Current and emerging pharmacotherapy for the treatment of gastroparesis.

INTRODUCTION: Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021. AREAS COVERED: We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting. EXPERT OPINION: We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.

Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation. METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the Nine Item ARFID Screen (NIAS) and the Pica, ARFID, and Rumination Disorder Interview-ARFID Questionnaire (PARDI-AR-Q). Gastric retention and fundic accommodation (for Gp and FD) were determined from gastric emptying scintigraphy. KEY RESULTS: At baseline, the proportion of children screening positive for ARFID on the NIAS versus PARDI-AR-Q was Gp: 48.5% versus 63.6%, FD: 66.7% versus 65.2%, HC: 15.3% versus 9.7%, respectively; p < 0.0001 across groups. Of children who screened positive at baseline and participated in the follow-up, 71.9% and 53.3% were positive 2 months later (NIAS versus PARDI-AR-Q, respectively). A positive ARFID screen in Gp or FD was not related to the presence/absence of delayed gastric retention or abnormal fundic accommodation. CONCLUSIONS & INFERENCES: ARFID detected from screening questionnaires is highly prevalent among children with Gp and FD and persists for at least 2 months in a substantial proportion of children. Children with these disorders should be screened for ARFID.

Epidemiology of functional dyspepsia and gastroparesis as diagnosed in Flemish-Belgian primary care: A registry-based study from the Intego database.

BACKGROUND: Dyspepsia is a prevalent condition in the general population. Besides organic causes, the differential diagnosis of dyspepsia includes functional dyspepsia (FD) and gastroparesis (GP) which share similar pathophysiological mechanisms and clinical presentation. So far, no study investigated the prevalence of FD and GP in a primary care in Belgium. METHODS: Data were obtained from Intego, a Flemish-Belgian general practice-based morbidity registration network. From 586,164 patients between 2000 and 2021, we selected patients with ICD-10 code for FD and GP. Patients with organic gastrointestinal diseases were excluded. We determined demographics and comorbidities of FD/GP. For prevalence and incidence calculation, we included those who consulted their general practitioners at least once in the given year. Pair-wise comparison was conducted to access the impact of comorbidities on risk of FD/GP. KEY RESULTS: Between 2011 and 2021, the prevalence of FD/GP ranged from 1.03% to 1.21%. The incidence of FD/GP ranged from 109 to 142 per 100,000 adults. In total 5242 cases of FD/GP were identified. These cases shared commonly coexisting diagnoses of gastroesophageal reflux disease (18.8%), irritable bowel syndrome (17.1%), and chronic constipation (18.7%). Patients with somatization/anxiety/depression had significantly higher risk of FD/GP, compared to the control (OR 1.38, 95% CI 1.19-1.61, p < 0.01). CONCLUSIONS AND INFERENCES: The prevalence (1.03%-1.21%) and incidence (109-142/100,000) of FD/GP in primary care over last decade appear to conflict with epidemiological research in the general population. The discrepancies suggest a potential lack of awareness of FD and GP among physicians and/or patients in Flemish-Belgium.

The High-Resolution Three-Dimensional Magnetic Detector System 3D-Magma Accurately Measures Gastric and Small Bowel Motility in People with Type 2 Diabetes with Neuropathy.

Gastroparesis is an important complication of diabetes. Motility disorders are underdiagnosed and can lead to unexplained hypoglycemia. Currently diagnostic options are limited. All established methods harbor certain disadvantages. The 3D-MAGMA system is capable of reliably measuring gastric and small intestinal motility. The aim of the current study was to determine if 3D-MAGMA is able to detect changes in intestinal motility in people with type 2 diabetes. 18 healthy volunteers and 19 people with type 2 diabetes underwent motility testing by 3D-MAGMA. In the control group the retention time in the stomach was 33.0 [min] compared to 75.3 [min] in the diabetes group. The median time in the duodenum was 12.7 [min] compared to 8.1 [min]. The time for the first 50 cm of the jejunum was 29.9 [min] compared to 28.2 [min]. Discussion and conclusion: 3D-MAGMA is able to detect changes in intestinal motility. Its clinical value might be useful in patients with fluctuating blood glucose levels and unexplained hypoglycemic episodes.

Effects of Spinal Cord Stimulation in Patients with Chronic Nausea, Vomiting, and Refractory Abdominal Pain.

BACKGROUND: Patients with chronic nausea and vomiting often also have chronic abdominal pain. Spinal cord stimulation (SCS) may provide pain control, but scarce data are available regarding the effect of SCS on chronic nausea and vomiting. AIMS: We aimed to determine the effect of SCS in patients with chronic nausea, vomiting, and refractory abdominal pain. METHODS: Retrospective chart review of 26 consecutive patients who underwent SCS trial for a primary diagnosis of nausea, vomiting and refractory abdominal pain. RESULTS: 26 patients underwent SCS trial, with an average age of 48 years. Twenty-three patients (88.5%) reported > 50% pain relief during the temporary SCS trial and then underwent permanent implantation. Patients were then followed for 41 (22-62) months. At baseline, 20 of the 23 patients (87.0%) reported daily nausea, but at 6 months and the most recent follow-up, only 8 (34.8%) and 7 (30.4%) patients, respectively, had daily nausea (p < 0.001). Days of nausea decreased from 26.3 days/month at baseline to 12.8 and 11.7 days/month at 6 months and at the most recent visit, respectively. Vomiting episodes decreased by 50%. Abdominal pain scores improved from 8.7 to 3.0 and 3.2 at 6 months and the most recent visit, respectively (both p < 0.001). Opioid use decreased from 57.7 mg MSO4 equivalents to 24.3 mg at 6 months and to 28.0 mg at the latest patient visit (both p < 0.05). CONCLUSIONS: SCS may be an effective therapy for long-term treatment of symptoms for those patients afflicted with chronic nausea, vomiting, and refractory abdominal pain.

Epidemiology, Etiology, and Treatment of Gastroparesis: Real-World Evidence From a Large US National Claims Database.

BACKGROUND & AIMS: Although gastroparesis carries a considerable health care and patient burden, associated epidemiological data are limited. To provide new real-world evidence for gastroparesis, we estimated disease prevalence, and investigated patient demographics and disease etiology in a large US claims database. METHODS: This retrospective, cross-sectional analysis used de-identified, longitudinal patient-level enrollment and billing data for adults from the Optum Clinformatics Data Mart database, a large US national administrative health insurance claims database. Prevalence was age-, sex-, and geographical region-standardized using the 2018 US census. Descriptive analyses of demographic and clinical variables and underlying disease etiologies were performed. RESULTS: The overall standardized prevalence of gastroparesis was 267.7 (95% confidence interval [CI] 264.8-270.7) per 100,000 US adults, whereas prevalence of "definite" gastroparesis (individuals diagnosed within 3 months of gastric emptying scintigraphy testing with persistent symptoms for more than 3 months) was 21.5 (95% CI 20.6-22.4) per 100,000 persons. Patients with gastroparesis had an overall Charlson Comorbidity Index score of 4.2, indicating substantial comorbidity burden. The most frequently documented comorbidities were chronic pulmonary disease (46.4%), diabetes with chronic complication (37.3%), and peripheral vascular disease (30.4%). Patients most commonly had a diabetic etiology (57.4%; type 1, 5.7% and type 2, 51.7%), followed by postsurgical (15.0%), drug-induced (11.8%), and idiopathic (11.3%) etiologies. CONCLUSIONS: New evidence is provided regarding the prevalence, patient demographics, and etiology of gastroparesis in the US general population. Wider availability of reliable objective gastric emptying measures and further education of medical professionals in recognizing and diagnosing gastroparesis would benefit future studies and improve understanding of disease epidemiology.

Gastroparesis.

Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.

The Short-Term Effects and Tolerability of Low-Viscosity Soluble Fibre on Gastroparesis Patients: A Pilot Clinical Intervention Study.

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that "low-viscosity" soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned.

Short-term outcomes of different modalities of pyloromyotomy versus gastric electrical stimulation in the treatment of gastroparesis: A systemic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis was to compare the short-term outcomes surrounding the efficacy and complication rate between different modalities of pyloromyotomy and gastric electrical stimulation (GES) in the treatment of gastroparesis. METHODS: Comprehensive, computerized research was performed on PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We additionally reviewed relevant articles, without any language limitations, published prior to April 15, 2020. Meta-analysis was conducted using RevMan 5.3 software. RESULTS: Three studies totaling 196 participants who had received 4 interventions, including single per-oral pyloromyotomy (POP), double POP, laparoscopic pyloromyotomy, and GES, were eligible for analysis. Compared to single POP, double POP achieved a better clinical response with a pooled relative risk (RR) of 1.27 (95% confidence interval [CI], 1.01-1.60, P = .04), while laparoscopic pyloromyotomy and GES showed no difference with a pooled RR of 0.89 (95% CI, 0.74-1.08, P = .23) and 0.87 (95% CI, 0.73-1.04, P = .13), respectively. As for the recurrence and complication rates, only GES showed a borderline significance of recurrence in comparison to single POP (RR 2.17, 95% CI, 1.00-4.71, P = .05), while there were no differences in the remainder of the comparisons. CONCLUSIONS: We conducted a detailed comparison of 3 modalities of pyloromyotomy and GES in the treatment of gastroparesis, with the results suggesting that double POP demonstrated better clinical success with similar recurrence and complication rates. In addition, GES may result in more recurrence amongst these interventions.

The gastric conduction system in health and disease: a translational review.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Pyloric distensibility in health and disease.

Until recently, gastric motility measurements in humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and gastric emptying tests, the latter being the only one performed in routine clinical care. Accurate and easy to use techniques were lacking to assess pyloric function in health and disease. Recently, pyloric distensibility has been developed and validated to assess pyloric opening. Several studies confirmed that pyloric distensibility was decreased in gastroparesis and correlated with gastric emptying as well as gastroparesis symptoms. In addition, pyloric distensibility may predict outcome of endoscopic techniques targeting the pylorus, namely intrapyloric botulinum toxin injection and gastric per-oral pyloromyotomy. Pyloric distensibility appears therefore to be a promising and useful new tool in the workup of gastroparesis patients.